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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

HIV and AIDS

Helena M. Swinkels; Angel A. Justiz Vaillant; Andrew D. Nguyen; Peter G. Gulick.

Author Information and Affiliations

Last Update: July 27, 2024.

Continuing Education Activity

Clinical prevention of HIV and AIDS is the cornerstone of controlling the global HIV pandemic,
which has claimed over 40.4 million lives worldwide, including 1.5 million children. Although a
cure remains out of reach, HIV is a chronic illness due to the effectiveness of antiretroviral
therapy. Combined with significant advancements in prevention, the goal of halting the global
HIV pandemic is now feasible. Current interventions acknowledge the complexity of clinical
management, considering socio-economic factors, patient-centered care, continuous quality
improvement, and the importance of social and regulatory environments to achieve optimal
patient and population outcomes.

This activity comprehensively reviews HIV transmission, pathophysiology, clinical

presentations, evaluation, up-to-date treatment, reporting, and implementation considerations for
specific population groups to prevent the diagnosis of AIDS. Clinicians increase their
knowledge, skills, and competence in managing HIV, improving patient outcomes, reducing
transmissions, and contributing to global efforts of disease eradication. The role of the
interprofessional team is highlighted, emphasizing collaboration among clinical, public health,
and interdisciplinary team members.

Objectives:

Determine the stage of HIV and related comorbidities to ensure timely diagnosis and
treatment for patients.

Apply the principles of antiretroviral therapy and prophylaxis for opportunistic infections
to prevent and manage adverse effects.

Interpret HIV treatment guidelines to ensure cultural sensitivity and maintain

confidentiality for individual patients and affected populations.

Collaborate with interprofessional team members to ensure continuity of care, improve

patient outcomes for HIV prevention and treatment, and mitigate the risk of AIDS.

Access free multiple choice questions on this topic.

Introduction
HIV was first identified in 1983 and has since claimed approximately 40.4 million lives
worldwide as of 2022. This number is staggering, and if left unchecked, HIV could become a
global health crisis. However, the research, development, and widespread availability of highly
active antiretroviral therapies (ARTs) have helped control the HIV pandemic. Likewise, advances
in the treatment of HIV and opportunistic infections have rendered the disease a manageable
chronic illness. Patients with HIV can live long and healthy lives. Preventing chronic diseases is
a top health priority for this population due to the underlying immunodeficiency.

Adequate resources and advances in prevention, treatment, and implementation science make the
United Nations General Assembly's 95-95-95 goals attainable. By 2025, the goal is to ensure
that 95% of patients with HIV are diagnosed, 95% of diagnosed patients receive ART, and 95%
of those prescribed ART achieve viral load suppression.[WHO. Global Health Sector HIV
Strategies 2022] Globally, HIV and mortality rates show a steady decrease. However, some
countries report an uptrend in the rate of infections, mostly where political or other turmoil is
occurring or where HIV is highly stigmatized.[UNAIDS. Global Report 2023] With
improvements in treatment, the number of patients with HIV is also increasing, with
approximately 37.7 million patients diagnosed in 2020 and 39 million patients diagnosed in 2022
—two-thirds of whom live in Africa.

HIV imposes high costs on both patients and the healthcare system. Infection with HIV increases
the risk of chronic disease, particularly cardiac and neurological. Although ART delays disease
progress, treatment does not cure HIV, causes adverse effects, and requires consistent,
prolonged connection to the healthcare system. Several barriers to universal treatment exist,
including public- and self-stigma, lack of adequate access to care, inappropriate care, and
costs. Using local clinical guidelines for managing HIV improves patient outcomes and prevents
HIV transmission. Clinical guidelines promote quality programming for prompt diagnosis,
treatment, and connection to care for patients with or at risk of acquiring HIV. Increasing the
involvement of community-led organizations in HIV testing and treatment and
integrating medical services for related health issues extend the reach of precise services,
improve linkage to care, and improve overall health. Supportive social and policy environments
regarding access to services, screening, reporting test results, and discrimination can safeguard
patients and the community.

This clinical reference focuses primarily on HIV-1 and is designed to review the
pathophysiology, clinical manifestations, and recommended treatment options for patients with
HIV, providing clinicians with concise and up-to-date guidance for managing HIV. The optimal
social and policy environments to support the HIV response, as recommended by the World
Health Organization (WHO), the Joint United Nations Programme for HIV/AIDS (UNAIDS),
the United States Centers for Disease Control (CDC), and state legislatures, with Florida
legislation provided as an example, are discussed. Please see StatPearls' companion resource,
"HIV-2 Infection," for more information.[1]

Etiology
HIV is part of the Retroviridae family in the Lentivirus genus. The virus mainly targets CD4+ T-
lymphocyte helper cells, leading to extreme immune suppression with a continuous loss of
cells. This suppression weakens the immune system and causes many clinical manifestations.
Untreated HIV eventually progresses to AIDS. At this stage, the immune system cannot prevent
infections, resulting in death due to opportunistic infections. Two main types of HIV include
HIV-1 and HIV-2. Although their genomes are structurally similar, they diverge significantly at
the amino acid level. The 2 viruses result from 2 different zoonotic transmissions of simian
immunodeficiency viruses and, as a result, have substantial differences in their severity,
transmissibility, and prognosis. Note that HIV-1 and HIV-2 are only 60% identical at the amino
acid level and have a mere 48% identity similarity at the nucleotide level.

HIV-1 and HIV-2 particles comprise a lipid membrane surrounding a protein capsid. The capsid
holds a nucleoprotein complex or core consisting of 2 identical copies of RNA and nucleocapsid,
integrase, and reverse transcriptase proteins. The capsid protein organizes into a lattice structure,
giving the capsid a characteristic conical shape. HIV is transmitted through various body fluids,
such as blood, amniotic fluid, breast milk, semen, pre-ejaculate, rectal fluids, and vaginal
fluids. HIV can be transmitted through sexual contact, during pregnancy and delivery,
and through fomites, such as reusable medical equipment or syringes. Please see StatPearls'
companion resource, "HIV Prevention," for more information.[1][2]

Epidemiology
HIV is a significant public health issue worldwide. HIV-1 causes most infections, with HIV-2
accounting for only 1 to 2 million infections. The prevalence of HIV-2 exceeds 1% of infections
only in West Africa, although infections occur less commonly on all continents, particularly in
cases with colonial or other ties to the area. According to the WHO HIV factsheet, there were 39
million patients with HIV at the end of 2022, with the majority (25.6 million) living in Sub-
Saharan Africa.[WHO. HIV Data and Statistics 2023.] In 2022, 1.3 million new cases of HIV
were reported worldwide, with 630,000 deaths related to HIV in the same year.

Although some countries report an increase in new infections, the overall global trend in HIV
incidence has decreased. In particular, significant gains prevent and treat HIV in eastern and
southern Africa, where the virus is most prevalent. From 2010 to 2022, 57% fewer new
infections and 58% fewer AIDS-related deaths occurred in the region. Progress is slower in other
areas, mainly where marked inequities and low prioritization of the HIV response exist. A study
of global trends in HIV among adolescents and young adults showed a decrease in incidence
from 34.5 per 100,000 population in 1990 to 22.7 per 100,000 population in 2019. However,
between 2010 and 2022 in Asia and the Pacific, a quarter of new infections affected people aged
between 15 and 24 and their partners, with some countries reporting nearly half of all new
infections in this population. In total, new HIV cases have decreased by only 14% in the region.

HIV incidence is increasing in some regions. The WHO Middle East and North African
regions had a 61% increase in the incidence of HIV between 2010 and 2022, the largest in the
world. Due to the low prevalence of HIV in this region, the number of people infected (about
16,000 people in 2022) is small relative to the 160,000 people estimated to be infected in Eastern
Europe and Central Asia in 2022. New HIV cases in this region increased by 49% between 2010
and 2022. Challenging legal environments, human rights violations, and military conflicts have
hindered the HIV response.

HIV diagnosis, treatment, and viral suppression rates vary across and within countries and
regions. Globally, women accounted for 65.8% of new HIV cases in 2019. However, diagnosis,
treatment, and viral suppression rates are lower among adolescent and adult men. For example, a
phylogenetic study in Uganda estimated that men are 1.5 to 1 times less likely to be virally
suppressed compared to women. Interventions that increase viral suppression rates among men
similar to women close the gender disparity in incident HIV cases. UNAIDS and WHO
identify 5 key populations who are disproportionately affected by HIV and warrant specific care
and support to reduce global transmissions—men who have sex with men, sex workers, people in
prisons and other closed settings, people who inject drugs, and transgender and gender-diverse
people.[UNAIDS. Global Report 2023.]

The vast majority of new HIV cases worldwide occur from sexual contact. Most of these
infections are transmitted through heterosexual contact due to the high number of infections in
Africa, where this mode of transmission is dominant. Most new HIV diagnoses in most other
regions of the world occur in men who have sex with men.[WHO. HIV Data and Statistics
2023.] In the United States, in 2021, 70% of all new infections were in men who have sex with
men, whereas only 22% occurred through heterosexual contact.[CDC. Basic Statistics
2023.] Drug use is another significant risk factor for HIV. According to a meta-analysis from
2008, approximately 3 million people who inject drugs are living with HIV
worldwide. According to the CDC HIV Factsheet, 1 in 10 new HIV cases in the United States
can be attributed to injection drug use either alone or in men who have sex with men who
report injection drug use. A systematic review evaluating the effectiveness of needle and syringe
exchange programs reported that adequate needle and syringe exchange programs are effective in
reducing the sharing and reuse of needles and syringes and HIV transmission among people who
inject drugs. Please see StatPearls' companion resource, "HIV Prevention," for more information.
[4][5][6][7][8]
Pathophysiology
The Retroviridae family is unique among viruses, with the RNA viral genome reverse-
transcribed into DNA before being integrated into the host DNA, resulting in lifelong infection.
The pathophysiological process is best known for HIV-1, with more recent research contributing
to the understanding of differences in HIV-2 and HTLV viral replication and biology. As the
primary host cellular receptor for HIV-1 and HIV-2 is the CD4+ antigen, T cells and
macrophages that express CD4+ are the primary viral targets. Envelope glycoprotein on the
surface of the viral particle facilitates viral entry into the host cell. Chemokine coreceptors 5
(CCR5) and 4 (CXCR4) on the host cell surface trigger a conformational change in the envelop
protein, which results in the fusion of the viral and host cellular membranes. The viral capsid is
released into the host cell when membrane fusion occurs.

The HIV-1 capsid remains intact or nearly intact until reaching the nuclear pore complexes on
the nuclear envelope of the host cell. Previously believed to occur in the cytoplasm, reverse
transcription is now believed to occur during or shortly after the capsid is imported into the
nucleus; the nuclear capsid is essential in the efficiency of reverse transcription. The precise
location and mechanism of reverse transcription and the role of the capsid have not been fully
elucidated. Some molecular studies suggest uncoating and reverse transcription begins in the
nucleus. In contrast, others suggest a partial uncoating of the viral capsid at the nuclear pore
complexes, with early stages of viral DNA production occurring near the nuclear envelope of the
host cell.

The viral reverse transcriptase enzyme initiates reverse transcription using host transfer RNA as
primers, which bind at the 5' ends of the 2 identical RNA strands and progress in a 5' to 3'
direction. Negative-sense single-stranded DNA is initially produced, with doubling of the strand
beginning part way along the viral genome. Elongation continues to the end of the genome, after
which each strand is synthesized using the other as a template. The viral integrase protein then
somewhat randomly integrates the double-stranded DNA into the host DNA. When viral
particles are formed, they can infect other host cells to propagate the infection. Within 2 days of
the initial mucosal exposure, HIV can be detected in the regional lymph node tissue. From here,
the virus only requires 3 days to be detected in the plasma.

Genomic diversification is an important aspect of the pathogenesis of HIV, leading to changes in

the severity of the disease and the response to ART. One of the primary driving factors for HIV-1
mutagenesis is the error rate of the reverse transcriptase encoded by the virus. According to
results from several studies, the error rate of HIV-1 group M reverse transcriptase (subtype B) is
100 to 1000 times higher than that of the cellular DNA polymerases. These errors are
incorporated into the viral genome and contribute to viral diversification. Other intrinsic and
extrinsic factors, such as recombination errors, host restriction factors, and depletion of
host deoxynucleoside triphosphates, can lead to viral mutagenesis and diversification, leading to
ART failure.[1]

In the initial phase of the infection, viral replication is rampant, with an exponential increase in
the plasma HIV RNA level due to the large population of susceptible CD4+ T cells without any
host immune response. Subsequently, a significant decline from the peak viremia level occurs
due to the HIV-specific immune response from the cytotoxic CD8+ T cells. After this decline,
the HIV replication settles when replication and infection continue, but the initial intense
immune response with associated symptoms resolves. The exact mechanisms involving the
failure of humoral immunity are not fully understood. T cells within B-cell follicles, particularly
the follicular T-helper cells and follicular regulatory T cells, are believed to be involved in poor
humoral immunity and HIV persistence in patients treated with ART. In addition, follicular
CD8+ cytotoxic T cells are relatively less abundant compared to their extrafollicular counterparts
in patients with HIV, likewise believed to contribute to disrupted immunogenesis.[2][3]
Histopathology
Lymphadenopathy exhibiting distinctive morphological changes is evident in patients with HIV.
In untreated cases, pronounced follicular hyperplasia emerges initially, marked by enlarged,
irregularly shaped follicles that occupy a substantial portion of the lymph node's cross-sectional
area. The mantle cell zones are absent or dramatically decreased. Centroblasts are the dominant
cell types; the germinal centers have a starry-sky appearance. Follicle lysis or fragmentation is
present when small lymphocytes infiltrate the follicle. Sinusoidal monocytoid B-cell hyperplasia
is also present. Mixed follicular hyperplasia is the intermediate stage between florid and
follicular involution. Here, the interfollicular area is relatively large compared to florid follicular
hyperplasia, and the follicles and interfollicular area are more cellular compared to those
observed in follicular involution.

In follicular involution, small, atrophic, and hypocellular follicles are observed. The germinal
centers contain hyalinized follicular dendritic cell meshworks with few germinal center B cells.
Hyalinized blood vessels are observed penetrating the follicles. Due to the scarcity of
lymphocytes, the interfollicular area is expanded with a washed-out appearance. Histiocytes and
polytypic plasma cells are abundantly present. Eventually, the lymph nodes enter the lymphocyte
depletion stage, characterized by the loss of germinal centers and the near absence of
lymphocytes. These lymph nodes contain medullary cords and sinusoids. The interfollicular area
primarily consists of histiocytes, plasma cells, and a few immunoblasts. Focal hyaline deposits
may be present with subcapsular and sinusoidal fibrosis.[4]

History and Physical

A medical history and physical examination include a review of systems indicated for patients
with confirmed or suspected HIV. Attention to signs and symptoms rule out other conditions in
the differential diagnosis that signal opportunistic infections or HIV-associated sequelae. The
clinical presentation stages the HIV infection and ensures that any concurrent conditions are
addressed. In addition to characterizing symptoms, the history identifies risk factors for HIV
transmission in a nonjudgmental manner, including sexual contact and behavior, drug use, and
blood transfusions. The sexual history should elucidate information regarding the number of
partners, sexual practices, frequency and type of barrier protection, and previous history
of sexually transmitted infections (STIs). Information about the HIV status of current and past
partners should also be obtained.

The drug use history should include the type and frequency of substances used, means of
administration, and source and sharing of equipment. A mental health assessment is essential for
identifying conditions such as depression, other mental illnesses, or substance use that may result
in barriers to care or contribute to the development of chronic diseases. Obtaining an
immunization history is crucial to determine which vaccines could offer future protection against
vaccine-preventable illnesses. For instance, Streptococcus pneumoniae, associated with adverse
outcomes in HIV-positive individuals, and hepatitis B, linked to a heightened risk of
hepatocellular carcinoma progression in patients with HIV, underscore the importance of such
proactive measures.

Social history is an integral part of any medical evaluation. In the context of HIV and AIDS, this
history provides insights into the patient's perceptions of and ability to adhere to treatment and
potential barriers to connection to healthcare services. Identifying resources of support assesses
living situation, income, insurance, social support, experiences of stigma, coping strategies, and
exposure to sexual or other violence. The United States National Institutes of Health (NIH)
describes 3 broad stages of HIV that develop over time—acute HIV, chronic or asymptomatic
HIV, and AIDS.[NIH. Stages of HIV Fact Sheet 2021.] The CDC maintains a staging system
based on CD4+ and AIDS-defining illnesses intended for surveillance.[10] The WHO has a
staging system based on clinical presentation for clinical or surveillance purposes in areas with
limited or no availability of CD4+ testing.[WHO. HIV Case Definitions 2007.][5][6][7]

Acute HIV

Approximately 90% of patients with acute HIV experience at least 1 symptom within the
first 4 weeks after primary HIV infection. These symptoms are typically mild, nonspecific, and
self-limited. Some patients present with more severe symptoms, known as acute retroviral
syndrome or seroconversion illness. These symptoms are listed below in order of decreasing
frequency.

Fever

Fatigue

Muscle pain

Skin rash

Headache

Sore throat

Swollen lymph nodes

Joint pain

Night sweats

Diarrhea

Symptom onset occurs acutely around 2 to 4 weeks (with a range of 4 days to 8 weeks) after viral
infection, just before the peak of viremia. Lasting an average of 18 days, the resolution of
symptoms coincides with the setting of a viral replication set-point approximately 30 days after
the initial viremia. Without treatment, higher viral load and increased severity and duration of
conversion illness are early predictors of a poor prognosis. Mucocutaneous ulceration is a
characteristic feature of acute HIV characterized by shallow, sharply demarcated ulcers that have
a white base surrounded by a thin area of erythema. Depending on the mode of transmission,
ulcers may be located on the oral, anal, penile, or esophageal mucosa. Acute aseptic
meningoencephalitis is reported as a clinical presentation of acute HIV-1.[2][8][9][10][11]

Chronic HIV

After HIV acquisition and subsequent setting of the viral set point, patients enter the chronic
phase of the infection. Most patients with chronic HIV remain asymptomatic before developing
AIDS. However, nonspecific fatigue may present, and persistent generalized lymphadenopathy is
usual. Generalized lymphadenopathy is characterized by at least 2 noncontiguous sites other than
inguinal nodes exhibiting enlarged lymph nodes for more than 3 to 6 months, not explained by
other lymphoproliferative or infectious causes.[4][12] Patients with chronic HIV without AIDS
can develop oropharyngeal candidiasis, recurrent vulvovaginal candidiasis, oral hairy
leukoplakia, disseminated cutaneous herpes simplex virus, and cervical dysplasia or cervical
carcinoma in situ.[13][14][15] Cutaneous manifestations such as seborrheic dermatitis, bacillary
angiomatosis, varicella-zoster virus reactivations, and molluscum contagiosum infections are
common and tend to be severe in patients with HIV.[16][17][18]

AIDS

Eventually, HIV progresses to advanced disease, particularly if left untreated or inadequately

treated. AIDS is diagnosed when specific AIDS-defining conditions are noted, regardless of the
CD4+ count. These AIDS-defining conditions, outlined by the CDC, include:
 Candidiasis of the digestive tract (other than thrush)

Candidiasis of the pulmonary tract

Invasive cervical cancer

Extrapulmonary or disseminated coccidioidomycosis, histoplasmosis, or cryptococcosis,

including cryptococcal meningitis

Chronic intestinal cryptosporidiosis or isosporiasis

Cytomegalovirus retinitis

Kaposi sarcoma

HIV encephalitis and HIV-associated neurocognitive disorder

Tuberculosis

Primary lymphoma of the brain

Non-Hodgkin lymphoma

Burkitt lymphoma

Mycobacterial infections

Pneumocystis jirovecii pneumonia

Progressive multifocal leukoencephalopathy

Salmonella septicemia

HIV-associated wasting syndrome [19]

These AIDS-defining illnesses tend to occur most frequently with low CD4+ counts <200
cells/mm3, which correlates with untreated advanced HIV as the total lymphocyte count depletes
over time.[20][21]

Evaluation
Testing is essential to confirm a diagnosis of HIV. Antibody, antigen-antibody, and nucleic acid
amplification tests are available for screening or confirming HIV in symptomatic illness. No
currently available testing technology can detect HIV during the initial viremic phase of the
infection, known as the window or eclipse period, which lasts up to 20 days. The following tests
are used to detect viral proteins:

Nucleic acid amplification tests: Detects HIV RNA in the blood 6 to 8 days after infection,
up to 33 days.

Antigen tests: Detect viral proteins such as p24 antigen as early as 13 to 20 days after
infection.

Antigen-antibody tests: Detect viral proteins as with other antigen tests, plus anti-HIV
immunoglobulin M (IgM) and IgG antibodies around 20 and 30 days, respectively, after
infection.[CDC. HIV testing 2024.]

In clinical settings, combination antigen/antibody (Ag/Ab) tests are recommended to identify

patients with HIV. These tests are available in most commercial laboratories and hospitals in
developed nations and are increasingly available worldwide. Ideally, the Ag/Ab test should be a
fourth-generation test capable of detecting HIV-1 and HIV-2 antibodies and the HIV-1 p24
antigen. If the initial positive test cannot cannot distinguish between HIV-1 and HIV-2 this
distinction, a supplemental antibody immunoassay is required. All initial positive test results are
followed by a second HIV test, preferably a test that is laboratory-based, to confirm a diagnosis
of HIV. The false positive rate of third- and fourth-generation tests is very low.

If the combination assay result is negative, no further testing is indicated unless HIV exposure is
too recent for detectable p24 antigen levels to have developed. If the initial Ag/Ab test result is
negative and early HIV is suspected, an HIV-1 nucleic acid amplification test to detect HIV RNA
should be performed. Specimens indeterminate on the initial Ag/Ab test or nonreactive or
indeterminate with the HIV-1– and HIV-2–specific antibody assay are followed up with an HIV-1
nucleic acid amplification test.[24]

An acute HIV case is diagnosed with a positive nucleic acid amplification test result in the
following settings:

A recent negative screening immunoassay result

A positive antigen-antibody immunoassay result, with a negative antibody-only

immunoassay

A nonreactive or indeterminate HIV-1– and HIV-2–specific antibody assay result

following a positive screening assay

A negative HIV-1 nucleic acid amplification test result in the last settings indicates a false-
positive HIV-1 test. When clinical suspicion for HIV is high and initial test results are
negative, testing should be repeated in 1 to 3 weeks. Home-based, point-of-care, or rapid tests are
essential to increase testing frequency or extend testing into populations that may otherwise not
get tested. As with other HIV tests, positive results from point-of-care testing should be
followed with standard laboratory, instrument-based immunoassays to confirm the diagnosis.
[22]

When the diagnosis of HIV is established, a baseline laboratory evaluation facilitates the staging
of HIV progression, selection of ART, and identification of comorbidities.[NIH. Guidelines for
HIV 2023.]

Quantitative CD4+ T-lymphocyte cell count

Quantitative plasma HIV-1 RNA viral load

Complete blood count, glucose, blood urea nitrogen, creatinine, liver enzymes, bilirubin,
urinalysis, serum lipids, and serology for hepatitis A, B, and C

HLAb*5701 test (if abacavir is being considered)

Genotypic drug-resistance assessment focusing on genes for reverse transcriptase and

protease in treatment-naive people, with the addition of integrase strand transfer inhibitor
(INSTI) for patients who have been treated with ARTs

Other tests may be indicated based on the history and physical examination, such as testing
for sexually transmitted infections, including Chlamydia trachomatis, Neisseria
gonorrhoeae, syphilis serology, opportunistic infections, or cancer

Viral load is the most important indicator of initial and sustained response to ART and aids in
ART selection. Some treatment regimes are ineffective in patients with high baseline viral loads.
Viral load should be monitored at entry into care, initiation of therapy, and
periodically afterward. CD4+ is the best indicator of immune function, disease progression, and
survival and determines the need to start prophylaxis for opportunistic infections. Blood must be
drawn for CD4+ testing before starting ART, but ART should not be delayed pending results. If
CD4+ is unavailable, the WHO staging system should be used. Monitoring of other CD
subsets is not recommended due to costs and lack of clinical utility. Routine testing for herpes
simplex IgG, cytomegalovirus IgG, and toxoplasma IgG is not recommended, given that these
tests do not delineate active disease versus previous exposure. Testing for serum cryptococcal
antigen should be considered in patients with a CD4+ count of 100 cells/mm3 or less. Please see
StatPearls' companion resource, "HIV Testing," for more information.[23]

Treatment / Management
The goal of HIV-1 therapy with antiretroviral medications is to achieve sustained virologic
suppression. According to current WHO and CDC guidelines, ART should begin after the
diagnosis is confirmed and an initial assessment is completed for all patients with HIV,
regardless of their immune status or clinical stage, unless a severe opportunistic infection is
present.[NIH. HIV Guidelines 2023] Management of HIV must include identifying
specific support required by the patient to maintain medication adherence, particularly for
marginalized patients. Treatment choice is initiated based on patient preferences and ability to
comply with a medication regimen.[WHO. Global HIV Strategies 2022.]

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse

transcriptase inhibitors (NNRTIs), INSTIs, and protease inhibitors are used in treatment-naive
patients. NRTIs inhibit viral replication by binding the viral reverse transcriptase and terminating
DNA prolongation in HIV-1 and HIV-2 infections. NNRTIs block DNA prolongation by binding
the viral reverse transcriptase at a separate site but are only active against HIV-1. INSTIs inhibit
the transcribed viral DNA from integrating into the host genome. Protease inhibitors block the
last step in the viral maturation process, rendering assembled viral particles immature and
noninfectious. The most common drugs within each class in the initial treatment of HIV are
listed below.[NIH. HIV Guidelines. 2023][23]

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

Abacavir (contraindicated for patients who are HLA-B*5701 positive)

Emtricitabine

Lamivudine

Tenofovir (tenofovir alafenamide or tenofovir disoproxil fumarate)

Zidovudine

Non-Nucleoside Reverse Transcriptase Inhibitors

Efavirenz

Rilpivirine

Doravirine

Etravirine

Nevirapine

Integrase Strand Transfer Inhibitors

Raltegravir

Elvitegravir with boosting agent cobicistat

Dolutegravir

Bictegravir
 Cabotegravir

Protease Inhibitors

Atazanavir

Darunavir

Fosamprenavir

Ritonavir-boosted lopinavir

Nelfinavir

Tipranavir

Other drug classes, such as CCR5 antagonists, fusion inhibitors, attachment inhibitors, capsid
inhibitors, and post-attachment inhibitors, are reserved for patients with multidrug-resistant HIV.

Recommended Therapy for Treatment-Naive Patients

Current guidelines recommend initiating INSTI-based therapy with a dual NRTI backbone before
conducting further laboratory testing for most patients with HIV. In select cases where the HIV
RNA level is <500,000 copies/mL, no coinfection with hepatitis B occurs, and no genotypic
resistance is present, a 2-drug regimen with dolutegravir and lamivudine can be considered first-
line. Tenofovir plus lamivudine or emtricitabine are the preferred NRTIs,
and bictegravir and dolutegravir are the preferred INSTIs due to their effectiveness, adverse
effect profiles, shorter duration to virological suppression, and lower propensity to develop
resistance. INSTI-based regimens achieve faster viral suppression compared to protease inhibitor
or NNRTI-containing regimens. The addition of other agents in the setting of advanced HIV on
presentation does not improve clinical outcomes at the onset of treatment and is not
recommended. Abacavir is no longer recommended as initial therapy due to the association with
cardiovascular disease, the risk of hypersensitivity, and the need for HLA B*5701
testing. Antiretroviral treatment should be started regardless of the CD4+ count to reduce a
combination of serious AIDS- and non–AIDS-related events and death from any cause if started
at diagnosis compared to a deferred initiation of treatment.[24][25][26][27][28]

Comorbid conditions affect HIV ART selection due to contraindications or co-benefits of

treatment, including the following:

Hepatitis B virus coinfection: Tenofovir-containing ART regimens are preferred as

tenofovir suppresses hepatitis B virus replication. ART regimens that use lamivudine or
emtricitabine without tenofovir should be avoided as they can result in the rapid
emergence of resistant hepatitis B virus.

Renal dysfunction: Tenofovir disoproxil fumarate is associated with proximal tubular

dysfunction and should be avoided in patients with an estimated glomerular filtration rate
of less than 60 mL/min/1.73 m2. Tenofovir alafenamide can be used unless the patient has
reduced renal function (estimated glomerular filtration rate <30 mL/min/1.73 m2) and is
not on dialysis, in which case no tenofovir formulation is indicated. The preferred regimen
is dolutegravir plus lamivudine, adjusted for renal function. Atazanavir should also be
avoided in patients with reduced kidney function.

Osteoporosis: Tenofovir alafenamide is associated with less bone loss and is preferred over
tenofovir disoproxil fumarate–containing regimens.

Pregnancy: Bictegravir, doravirine, cabotegravir, dolutegravir/lamivudine combination,

and dolutegravir/rilpivirine combination should not be initiated during pregnancy due to
 limited data to support their safety. Cobicistat-containing regimens should not be used
during pregnancy due to inadequate drug levels.[NIH. HIV Guidelines 2023.]

When laboratory test results are available, the initial regime may be adjusted. A dual NRTI
coformulation plus an antiretroviral from another class is prescribed for patients unable to take
an INSTI-based regimen. For example, the protease inhibitor darunavir is boosted with
cobicistat, ritonavir, or an NNRTI, either efavirenz or rilpivirine.[15]

Recommended Therapy for Treatment-Experienced Patients

Treatment-experienced patients require a wider range of antiviral options compared to initial

treatment due to an increased probability of multidrug-resistant strains of HIV. Notably, the
barrier to resistance is higher with combination antiretroviral therapy containing later-generation
integrase inhibitors, including dolutegravir and bictegravir. However, emerging reports of
increasing resistance to this class are apparent. Common resistance mutations identified at the
initiation of antiretroviral therapy in treatment-experienced patients include M184V and KS65R
with tenofovir, K103N/S in NNRTIs, and thymidine-analogue mutations in NRTIs.[29][30][31]
[32]

Initial therapy remains the same for treatment-naive patients with the goals of maintaining long-
term virological suppression and limiting the progression of the disease. Patients still require 2
to 3 active agents against HIV to reduce the risk of virological failure and drug resistance. The
regimens typically include an NRTI backbone with NNRTI and an integrase or protease inhibitor.
The NADIA and REVAMP trials, among others, indicated that resistance to first-line
antiretroviral agents did not indicate failures in virological suppression with second-line agents
incorporating classes from the first-line agents, suggesting that drug-resistance assay may not
always be required. However, given that these results were not primary endpoints, these findings
should be interpreted cautiously, and drug-resistance assays may still yield better choices in well-
resourced clinical settings. A genotypic drug-resistance assay is indicated when the patient is still
taking the ART or as soon as possible after ART discontinuation.[24][33][34]

The challenge with antiretroviral agent resistance is that resistance may not predict clinical
outcomes accurately.[35] In cases of complex drug resistance, phenotypic assays may be
considered to test drug susceptibility against HIV.[36] When possible, drug resistance therapies
can guide alternatives to first-line NNRTIs, integrase, or protease inhibitors. The therapies may
include second-generation NNRTIs, capsid inhibitors, pharmacologically boosted protease
inhibitors, and later-generation integrase inhibitors. Policies should be instituted nationally or
regionally for presentations requiring third-line therapy. In cases of resistance to all available
therapy, continuing the regimen that the patient best tolerates and maintains some level of
virological suppression is important. Novel antiretroviral agents approved by the United States
Food and Drug Administration, such as capsid or attachment inhibitors, may be considered when
conventional treatment options result in virological and clinical failure. Future drugs based on
monoclonal antibodies are being developed, informing treatment for treatment-experienced
populations.[37][38][39][40][41]

Recommended Therapy for Patients on Preexposure Prophylaxis

Patients on preexposure prophylaxis with tenofovir alafenamide or tenofovir disoproxil fumarate

with emtricitabine who subsequently acquire HIV require resistance testing before initiating
therapy. They can be initiated on INSTI-containing regimens outlined above while genotype or
resistance testing is pending. Patients who acquire HIV after receiving cabotegravir for
preexposure prophylaxis require INSTI genotyping before beginning therapy with an INSTI-
based regimen. Although the results are pending, a boosted protease inhibitor regimen containing
darunavir and a tenofovir-based dual NRTI coformulation should be used. Please see StatPearls'
companion resource, "Preexposure Prophylaxis for HIV Prevention," for more information.[24]
Therapy Considerations for Patients With HIV-2 Infections

Current recommendations for treating HIV-2 are primarily based on single-arm or observational
studies, as most research and treatment efforts have focused on HIV-1. The initial regimen for
managing HIV-2 should include 2 NRTIs plus a second-generation INSTI or a ritonavir-boosted
protease inhibitor.[NIH. HIV Guidelines 2023.] Tenofovir disoproxil fumarate and emtricitabine
are the preferred NRTIs. Dolutegravir is recommended as the preferred INSTI. Darunavir and
lopinavir are more active against HIV-2 compared to other protease inhibitors and are the
preferred agents. Two-drug regimens to treat HIV-1 and any regimen containing NNRTIs are
ineffective against HIV-2 and should not be used in these infections.[42]

Drug-resistance assays for HIV-2 are limited to research laboratories, complicating the
management of these infections. Current data suggest that HIV-2 is susceptible to NRTIs;
however, HIV-2 is more likely to develop resistance compared to HIV-1. Patients with HIV-2
mutations may exhibit complex patterns of protease inhibitor cross-resistance, making sequential
regimens ineffective for patients with this infection. In vitro studies report strong efficacy for
INSTIs against HIV-2. Clinical data regarding mutations and efficacy of the most commonly
used INSTI, such as dolutegravir, are limited, especially in those previously exposed to other
INSTIs. Further research is needed to understand resistance patterns for antiretrovirals in patients
with HIV-2.[43][44]

Opportunistic Infections

In addition to rapid ART initiation, prophylaxis for opportunistic infections should be started
based on the level of immunosuppression.

Pneumocystis jirovecii (previously P carinii): Prophylaxis is indicated for patients with

thrush on presentation, a CD4+ count of less than 200 cells/mm3 or a CD4+ count <14%.

Cryptococcus neoformans and Cryptococcus gattii: Patients with a CD4+ count of less
than 100 cells/mm3 and a positive serum cryptococcal antigen result require prophylaxis.

Histoplasma capsulatum: Prophylaxis is recommended in areas where histoplasmosis is

endemic and the patient's CD4+ count is less than 150 cells/mm3.

Mycobacterium avium complex infection: If patients with HIV are rapidly initiated on
ART, prophylaxis for Mycobacterium avium complex is not required. Patients with a
CD4+ count of less than 50 cells/mm3 without ART should receive prophylaxis.

Toxoplasma gondii: Patients with CD4+ counts less than 100 cells/mm3 who have positive
test results for toxoplasma antibodies require chemoprophylaxis.[26]

In patients with a severe opportunistic infection, rapid initiation of ART can result in immune
reconstitution inflammatory syndrome.[23] The opportunistic infection should be treated before
initiating ART to decrease the risk. Initiate ART within two weeks of initiating treatment for
most acute opportunistic infections, except acute cryptococcal meningitis.[45] Patients with
cryptococcal meningitis may commence HIV therapy within 2 to 4 weeks of antifungal therapy.
HIV treatment should be initiated within 2 weeks of tuberculosis treatment in patients who have
active tuberculosis, especially if they have severe immunosuppression (CD4+ count <50
cells/mm3); however, if evidence of tuberculous meningitis is detected, ART should be given
with high-dose corticosteroid treatment.[24]

Recommended Therapy for Prophylaxis of Opportunistic Infections

Prophylaxis and treatment in HIV-infected patients with opportunistic infections is dependent on

the level of immunosuppression for the patient and the isolation of any causative
pathogens. Improving the underlying cause of the immunosuppression by treating HIV is
recommended when managing opportunistic infections.[46] Given the high risk of P jirovecii
with CD4+ counts <200 cells/mm3 or CD4+ count <200 cells/µL or a CD4+ count <14%, low-
dose trimethoprim/sulfamethoxazole (co-trimoxazole) prophylaxis is recommended, which
protects against cerebral toxoplasmosis, bacterial infections, and malaria in endemic settings.[47]
[48] Alternatives for sulfur allergy where desensitization is not feasible include inhaled
pentamidine, dapsone, or atovaquone.[49] Hypoglycemia must be monitored with the
administration of pentamidine, whereas G6PD deficiency needs to be assessed before starting
dapsone.[50][51] Atovaquone can be considered but may not be as efficacious. Prophylaxis is
often discontinued after the CD4+ count returns to >200 CD4+ cells/mm3 for 3 or more months
in patients on antiretroviral therapy.[52][53]

For the treatment of P jirovecii, weight-based dosing of trimethoprim/sulfamethoxazole (co-

trimoxazole) for 21 days is recommended in addition to high-dose steroids to manage the
progressive respiratory complications of acute pneumonia and reduce mortality risk. Alternatives
include primaquine with clindamycin and intravenous pentamidine for 21 days. Primary
prophylaxis of toxoplasmosis, where the risk is greatest with a CD4+ count <100 cells/mm3, is
also covered by low trimethoprim/sulfamethoxazole (co-trimoxazole). Alternatives in the event
of a non-severe allergy to sulfur include dapsone with pyrimethamine and calcium
folinate. Discontinuation of primary prophylaxis may be considered if the CD4+ count is >200
cells/mm3 for 3 or more months in individuals on antiretroviral therapy.[54][55][56]
[57] Vaccinations should be encouraged for patients with HIV, as these may reduce the risk of
mortality from influenza, pneumococcal, and meningococcal pneumonia and reduce the risk of
other blood-borne viral infections.[58][59][60][61] Given the higher risk of human
papillomavirus–related cancers in patients with HIV, human papillomavirus vaccination is
recommended.[62] Please see StatPearls' companion resource, "Prevention of Opportunistic
Infections in HIV/AIDS," for more information.

Monitoring Following Initiation of Treatment

When treatment is initiated, the patient's HIV viral load should be evaluated in 2 to 4 weeks and
no later than 8 weeks. The viral load can be rechecked every 4 to 8 weeks to ensure the levels
decline. Virologic suppression to undetectable levels (defined as an HIV RNA level
of <200 copies/mL) may take up to 24 weeks of continuous therapy. If the HIV RNA level has
not declined by 2 log10 copies/mL within 12 weeks and adherence is confirmed, evaluation for
resistance with genotype testing for the patient's regimen is recommended. Genotype resistance
testing should also be obtained if virologic suppression is not achieved.[13] When viral
suppression is established, the viral load should be monitored every 3 to 4 months.[7] An HIV
RNA level that remains persistently below this lower limit of detection demonstrates sustained
virologic suppression—the primary goal of HIV therapy. Please see StatPearls' companion
resource, "HIV Antiretroviral Therapy," for more information.

Inadequate Viral Suppression and Development of Resistance

When inadequate viral suppression occurs, the HIV viral load and selection pressure increase,
inducing mutations favorable to resistance against active antiretroviral treatments. Virological
failure occurs when HIV viral is above 1000 copies/mL on 2 separate and consecutive
measurements over 3 months while on current antiretroviral treatment for 6 months or
longer. This condition can result in clinical failure, described as a new event or recurrence of
WHO stage 4 severe immunodeficiency after 6 months of current effective antiretroviral
treatment. Clinical failure suggests concern for antiretroviral resistance while a patient adheres to
effective antiretroviral treatment for 6 months or longer.[63] Given HIV has an RNA genome
prone to mutations, selection pressure from active antiretroviral agents during reverse
transcriptase can encourage drug-resistant mutants that lead to virological failure, clinical failure,
and eventually immunological failure, defined as a CD4+ count of 250 cells/mm3 or less.[64]
[65] Thus, while trials such as NADIA and REVAMP indicated treatment regimens incorporating
antiretroviral agents with prior resistance is feasible, the theoretical basis of how HIV develops
new mutations with inadequate viral suppression should be considered by the treating clinician in
managing treatment-experienced patients.[33][34]

Immunological Recovery

In patients who had a baseline CD4+ count of 250 cells/mm3 or less at diagnosis or
immunological failure while on antiretroviral treatment but then subsequently recovered a CD4+
count at or above 500 cells/mm3, immunological recovery constitutes only a minority of all
patients on effective antiretroviral treatment. The reasons are often multifactorial, including
adherence, baseline CD4+ count at diagnosis, the age and sex of the patient, the type of initial
antiretroviral agents initiated at diagnosis and any delays, and the patient's baseline functional
status.[66][67][68] When immunological recovery does occur, the timeline is typically over
many months or years but depends on multiple factors, including the class of antiretroviral
therapy, the baseline functional status of the patient, and treatment adherence. Conversely,
inadequate immunological responses are associated with an increased risk of serious non-AIDS
events and mortality in patients with HIV. Therefore, the treating clinician needs to monitor the
CD4+ count in patients undergoing treatment with antiretroviral agents for potential sequelae.
[69][70]

Differential Diagnosis
HIV should be considered in any patient with recurrent serious infections. Other conditions that
may have similar effects on the patient's immune system include:

Severe malnutrition

Severe combined immune deficiency syndrome

Chemotherapy-induced immunosuppression

The differential diagnosis in patients who present with acute HIV includes:

Mononucleosis

Toxoplasmosis

Viral hepatitis

Systemic lupus erythematosus

Toxicity and Adverse Effect Management

When prescribing antiretrovirals, a wide variety of potential drug-drug interactions, toxicities,
and other adverse effects must be considered. Consultation with a pharmacologist is
recommended. Some common reactions are listed below.[NIH. HIV Guidelines 2023.]

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

Abacavir is contraindicated for patients who are positive for the HLA-B*5701 allele due to
the risk of hypersensitivity reactions. Pretesting is required before prescribing any regimen
containing abacavir. Some studies have also demonstrated increased cardiovascular risk
with abacavir.

Tenofovir alafenamide is associated with higher lipid levels and weight gain but is
associated with less renal toxicity compared to tenofovir disoproxil fumarate.

Tenofovir disoproxil fumarate is associated with renal toxicity; proximal tubulopathies,

 such as Fanconi syndrome; and acute or chronic renal insufficiency, particularly when
combined with boosters. Tubulopathy can cause osteomalacia, and tenofovir disoproxil
fumarate can also cause decreased bone density.

Emtricitabine has been associated with hyperpigmentation of the palms and soles.

Didanosine and stavudine are no longer used due to severe adverse reactions and toxicity,
such as fatal lactic acidosis, pancreatitis, and peripheral neuropathy. Lamivudine can rarely
be associated with pancreatitis.[71][72][73][74]

Non-Nucleoside Reverse Transcriptase Inhibitors

Doravirine, efavirenz, and rilpivirine have the potential for cytochrome P450 (CYP)
enzyme drug interactions.

Efavirenz can also cause dyslipidemia, rash, and QTc interval prolongations. The drug has
the potential for short- and long-term psychiatric complications, suicidality, catatonia, and
late-onset ataxia and encephalopathy.

Rilpivirine can cause QTc interval prolongation but does not appear to be increased
beyond 48 weeks compared to efavirenz. The drug is less commonly associated with
depression, suicidality, and rash compared to efavirenz.[75][76][77][78][79]

Integrase Strand Transfer Inhibitors

All drugs of this class can cause weight gain compared to other antiretroviral classes.

Several drugs inhibit creatinine excretion without affecting glomerular filtration, including
bictegravir, dolutegravir, and cobicistat.

Bictegravir is a substrate for the enzymes CYP3A4 and UGT1A1 (uridine diphosphate
glucuronosyltransferase 1A1) and has the potential for drug-drug interactions. Examples
include aluminum- and magnesium-based antacids, where bictegravir should be
administered 2 hours before or 6 hours after, and rifampicin, a potent CYP3A inducer.

Early studies suggested that dolutegravir exposure during conception may be associated
with neural tube defects. However, a large cohort study of over 4 million pregnancies in
the United States in 2023 did not identify an increased risk of neural tube defects among
infants. Clinicians should discuss the current evidence when prescribing medications to
people of childbearing potential.

Raltegravir can increase creatinine kinase and less frequently cause myopathy and
rhabdomyolysis. The drug is known to cause severe hypersensitivity reactions, including
Stevens-Johnson syndrome and toxic epidermal necrosis. As a UGT1A1 substrate,
the potential for drug-drug interactions is recognized. Rarely, raltegravir has been
associated with depression and suicidal ideation in patients with preexisting psychiatric
conditions.

Cobicistat is an INSTI used exclusively as a pharmacokinetic enhancer of certain protease

inhibitors and INSTIs. The drug strongly inhibits CYP3A4, resulting in significant
potential for drug-drug interactions. Cobicistat must be discontinued in severe hepatic
impairment. Similar to other INSTIs, the drug can increase creatinine excretion without
impacting glomerular filtration.[80][81][82][83][84]

Protease Inhibitors
 Protease inhibitors other than atazanavir are associated with an increased risk of
cardiovascular events.

Atazanavir and darunavir are both CYP3A4 inhibitors and substrates with the potential for
many drug interactions. Both are co-formulated with cobicistat or ritonavir due to their
ability to boost therapeutic levels of atazanavir and darunavir.

Atazanavir coformulations can cause indirect hyperbilirubinemia, nephrolithiasis,

cholelithiasis, nephrotoxicity, and gastrointestinal adverse effects.

Darunavir coformulations can cause skin rash, gastrointestinal adverse effects, and
hepatotoxicity, particularly in patients with preexisting liver disease.[85][86][87][88]

CCR5 Inhibitor

Maraviroc adverse effects are uncommon, but when they occur, they are typically constitutional
and include gastrointestinal upset and fever.[89]

Fusion Inhibitors

Enfurvitide, an injectable antiretroviral agent, can be associated with injection site reactions,
including granuloma annulare and other symptomatic lesions.[90]

Capsid Inhibitors

The phase III clinical trial of lenacapavir involving 72 patients showed no serious adverse effects
(grade 3 or above), with only injection site reactions and gastrointestinal symptoms
identified. However, given the small numbers involved, post-marketing reports should be
reviewed.[39]

Attachment Inhibitors

The phase III trial of fostemavir involving 371 patients showed mild gastrointestinal adverse
effects that led to treatment discontinuation. However, given the small cohort, post-marketing
reports should be reviewed. Various drug interaction tools exist online, allowing clinicians to
access bedside information. When managing these potential adverse effects, the treating clinician
should balance the competing priorities of maintaining virological suppression and reducing
future antiretroviral class resistance with patient tolerance and concerns of long-term adverse
effects. Considering the individual's circumstances strengthens the therapeutic relationship and
encourages treatment adherence.[40][91]

Staging
Staging systems can be used for clinical or surveillance purposes to assess the rate of progression
to more advanced stages, assist in monitoring the HIV burden at a population level, plan for
prevention and care, and evaluate interventions. The CDC published the current definitions of
HIV surveillance cases in 2014. The definitions of surveillance cases are not intended for clinical
decision-making. HIV testing confirms the diagnosis and determines acute infection in stage
0, and the CD4+ count determines stages 1 to 3. All surveillance cases are assumed to be HIV-1
unless laboratory evidence indicates HIV-2. The criteria for stage 0 supersede and
are independent of the criteria used for other stages.[19]

Confirmed HIV Case

For all adults, adolescents, and children aged 18 months and older:

A second, different HIV test confirms a positive result from an initial HIV antibody or
antibody-antigen test.
 Clinical criteria can be used where HIV test results have not been recorded, but other
presumptive evidence exists, such as the history of therapy for HIV or an AIDS-defining
illness.

Stage 0

This stage is defined by a positive test result within 180 days of:

A negative or indeterminate test result

A negative initial immunoassay result followed by a positive nucleic acid amplification

test result to confirm acute infection

A positive nucleic acid amplification test result following a positive antigen or antigen-
antibody test result but unconfirmed by a second test

Stages 1 to 3

These stages are determined based on the CD4+ count for all people aged 6 and older (separate
criteria exist for infants aged younger than 1 and children aged 1 to 5):

Stage 1: 500 or more cells/µL

Stage 2: 200 to 499 cells/µL

Stage 3: less than 200 cells/µL

Globally, case definitions for HIV vary by country based on the testing technologies most
appropriate for use in the local context. The WHO recommends test-based confirmation in adults
and children aged 18 months or older to require a positive result from a rapid or laboratory-based
HIV antibody, antigen, or virological test, confirmed by a second positive test result relying on
different antigens or different test operating characteristics. Advanced HIV is confirmed by the
diagnosis of a condition associated with advanced disease or a CD4+ count of less
than 200 cells/mm3 in an adult or child with HIV. The WHO's clinical staging for HIV can be
used for clinical and surveillance purposes in resource-limited areas where CD4+ testing may be
unavailable.[WHO. HIV Case Definition 2007.] Advanced disease is defined as stage 3 or 4.

Stage 0 or Primary HIV Infection

Patients have 1 or more symptoms associated with acute HIV or a constellation of symptoms
consistent with acute retroviral syndrome.

Stage 1

In stage 1, patients are asymptomatic or have persistent generalized lymphadenopathy, defined

as enlarged lymph nodes (>1 cm) in 2 or more non-contiguous sites (excluding inguinal nodes)
not explained by any other cause.

Stage 2

In this stage, patients show unexplained weight loss (moderate degree, <10% of body weight),
recurrent respiratory tract infections, herpes zoster exacerbations (mild-to-moderate severity),
angular cheilitis, recurrent oral ulcerations, papular pruritic eruptions, seborrhoeic dermatitis, or
fungal fingernail infections.

Stage 3

In stage 3, patients experience severe weight loss (>10% of body weight); unexplained chronic
diarrhea; persistent fever; oral candidiasis; oral hairy leukoplakia; pulmonary tuberculosis;
severe invasive bacterial infections, such as pneumonia, empyema, osteomyelitis, meningitis, and
bacteremia; acute necrotizing ulcerative stomatitis; gingivitis or periodontitis; or unexplained
anemia, neutropenia, or thrombocytopenia for more than 1 month.

Stage 4 or AIDS

In this stage, patients develop HIV wasting syndrome; pneumocystis pneumonia; chronic herpes
simplex infection; esophageal candidiasis; extrapulmonary tuberculosis; Kaposi sarcoma;
toxoplasmosis; HIV encephalopathy; extrapulmonary cryptococcosis infections; disseminated
nontuberculous mycobacterial infections; progressive multifocal leukoencephalopathy;
pulmonary candidiasis; cryptosporidiosis; isosporiasis; cytomegalovirus retinitis (or in an organ
other than liver, spleen, or lymph nodes); disseminated mycoses, such as histoplasmosis,
coccidioidomycosis, and penicilliosis; recurrent salmonella septicemia; lymphoma (cerebral or
B-cell non-Hodgkin); invasive cervical carcinoma; or visceral leishmaniasis.

The WHO defines HIV wasting syndrome as the presence of unexplained weight loss greater
than 10% of the body weight, with the presence of either unexplained chronic diarrhea or
unexplained fever for 1 month or more. WHO clinical stage 4 and the CDC criteria for AIDS
are almost identical.[13] A wide variety of studies in resource-limited settings have evaluated the
utility of the WHO staging system for predicting immunological status defined by the CD4+
count. The findings indicate highly variable sensitivity and specificity across various CD4+ cut-
off levels, questioning the utility for clinical decision-making. This issue underscores the
importance of expanding the availability of CD4+ and viral load testing and the WHO and CDC
recommendations to offer treatment to all patients who are HIV positive.[WHO. Global HIV
Strategies 2022-2030.][16][14][15][35][43][44]

Prognosis
Without therapy, HIV infections are invariably fatal. However, effective ART with sustained
virologic suppression dramatically improves the clinical outcomes for patients with HIV.
According to a meta-analysis from 2017, life expectancy in high-income countries is estimated to
be 43.3 years if ART begins at 20, and 32.2 years if ART begins at 35. In low- to middle-income
countries, life expectancy is estimated to be 28.3 years and 25.6 years if ART starts at 20 and 35,
respectively. In all regions, regardless of income, life expectancy after starting ART has
improved, reflecting improvements in therapy and management such as improved ART
regimens, earlier initiation of ART, and better socioeconomic and adherence support.[92]

Viral suppression is the key determinant of prognosis. Patients who achieve virologic
suppression for at least 3 years without full immunologic recovery (CD4+ count <200
cells/mm3) have 2.6 times greater all-cause mortality compared to those who achieve
immunologic recovery (CD4+ >200 cells/mm3). Treatment at diagnosis is associated with
improved outcomes and better immune system recovery. Delaying ART until the patient's CD4+
count is less than 200 cells/mm3 decreases the likelihood of the CD4+ count normalizing after
multiple years of otherwise effective antiretroviral therapy, thereby increasing the patient's risk of
AIDS and non-AIDS-related morbidity and mortality. Other factors correlating with poor
immunologic recovery include older age, lower nadir CD4+ count, and extended ART initiation
to viral suppression time. Hepatitis C, hepatitis B, and active injection drug use are identified as
important factors contributing to higher morbidity and mortality among patients with HIV-1. For
people who inject drugs, socioeconomic and adherence support should be offered, mainly if
treatment is unavailable.[93][94][95]

Complications
Complications Related to HIV

The advent of ART has dramatically decreased the incidence of opportunistic infections and
HIV-associated malignancies. However, progression to AIDS remains a significant complication
of HIV. Screening and monitoring are warranted for AIDS-defining illnesses as appropriate to
the patient's clinical status. In addition, screening and monitoring for specific HIV- and ART-
related complications are listed below:

HIV-associated neurocognitive disorders and psychiatric complications, with the use of

efavirenz and, less frequently, rilpivirine and other INSTIs

HIV-associated distal symmetric polyneuropathy

HIV-associated lipodystrophy

Mitochondrial toxicity of HIV NRTIs

HIV-associated Kaposi sarcoma inflammatory cytokine syndrome and multicentric

Castleman disease

Hematological malignancies, including primary effusion, follicular, non-Hodgkin, Burkitt,

and diffuse large B-cell lymphomas [96][97][98]

Please see StatPearls' companion resources, "Acquired Immune Deficiency Syndrome," "HIV
Neurocognitive Disorders," and "HIV-Associated Lipodystrophy" for more information.

ART-Related Complications

The advent of ART has also raised the risk of cardiovascular disease morbidity and
mortality. Patients with HIV experience age-related comorbidities such as cardiovascular disease
more frequently, and much of the long-term care for patients with HIV focuses on minimizing
cardiovascular risks. Multiple different factors contribute to increased cardiovascular risk for
patients with HIV, including:

The prevalence of dyslipidemia among patients with HIV, with and without ART, is high.

Glucose intolerance or diabetes frequently occurs in patients receiving ART; this may be
due to specific ART drugs, such as earlier-generation protease inhibitors.

Multiple ART regimens are associated with weight gain.

Weight gain is common among patients on ART and is 1 of the significant contributors to
cardiovascular risk for patients with HIV. The exact mechanisms involved are unknown. Some
ART agents contribute more to weight gain compared to others. INSTIs are associated with more
weight gain compared to protease inhibitors or NNRTIs, and tenofovir alafenamide is associated
with more weight gain compared to tenofovir disoproxil fumarate, abacavir, or zidovudine.
Current guidelines recommend lifestyle modification counseling from the onset of ART to
mitigate weight gain and metabolic complications. Routine screening for glucose intolerance,
diabetes, and hyperlipidemia is recommended.[5][99]

Deterrence and Patient Education

Education, support, and counseling from the interdisciplinary care team are essential for patients
with HIV. Patients can be referred to organizations such as the CDC or NIH, which offer freely
accessible education.[NIH. Fact-sheets.]

HIV Treatment

Patients should be informed about the need for regular labwork and follow-up. They should also
be encouraged to keep all medical appointments and speak freely and openly with their clinician
to ensure that adverse effects, potential barriers to treatment, and other health concerns can be
addressed effectively. Patients undergoing HIV treatment require consistent education and
counseling to promote medication adherence, including the importance of starting ART as soon
as possible after diagnosis and the need to take the prescribed medications in compliance.

Medication adherence is essential to achieve HIV viral load suppression. Viral load increases
within weeks of stopping HIV medications and enhances the risk of developing resistant
organisms, complications from HIV, and transmission. Overcoming the challenges with
medication adherence includes seeking support through counseling, support groups, or consistent
communication with the treating teams. Patients should be offered home nurse visits, blister
packs, or automated reminders to support adherence.

Identifying the signs and symptoms that indicate toxicity from ART and the recommended next
steps should be relayed when educating patients. Minor adverse effects, such as nausea upon
initiation of therapy, can be managed with over-the-counter medications. Signs and symptoms of
liver or kidney injury should lead patients to seek immediate medical care. Patients should be
aware of the potential for drug-drug interactions and the importance of the pharmacist in
managing their medications. They should be encouraged to document their medication regimen
to maintain self-efficacy in treatment. Patients with HIV are at elevated risk of cardiac and
metabolic complications, may face complications that affect nutrition, and may need to avoid
certain foods due to the immunocompromised state. Lifestyle modifications to encourage healthy
eating, regular exercise, and the management of other risk factors, such as smoking, are
recommended.

Prevention of HIV Transmission

Patients with HIV are often highly motivated to prevent transmission to others, particularly when
they have a partner who is not infected with HIV. Recent data in the United States reveal
that every 10% increase in viral suppression on a population level is associated with a 4%
decline in the incidence of HIV in the subsequent year. Clinical education and emphasis on
undetectable equals untransmittable are crucial elements of HIV treatment, benefiting both the
patient's health and that of their partner or partners. People of child-bearing age may be
concerned about the transmission of HIV during pregnancy and should be aware of the options
for treatment and the benefits of planning.

People with an undetectable viral load may continue to make proactive decisions to protect
people within immediate contact. The person can correctly and consistently use condoms, choose
sexual activities with lower risk, encourage their partners to take preexposure prophylaxis, and
avoid sharing needles, syringes, and other drug injection equipment. People may be required to
disclose their HIV or other communicable disease status, for example, to clinicians in
jurisdictions with these requirements or to healthcare regulatory authorities if they provide
healthcare services.[19]

Stigma, Discrimination, and Mental Health

Diagnosis with a chronic illness can be a significant source of stress for anyone, given the
medical burden on lifestyle. The diagnosis can challenge one's sense of well-being or complicate
existing mental health or other conditions. Individuals may feel sadness, hopelessness, or anger.
In addition to the challenges of a new diagnosis of a serious chronic illness, patients with HIV
face further difficulties due to stigma and discrimination, including self-stigma. Self-
stigma occurs when patients with HIV internalize the negative opinions of others, such as
believing only certain kinds of people acquire HIV or that they deserve to contract the disease of
their behaviors.

The need to disclose HIV status to sexual or injection partners before sex or drug use can be
uncomfortable and provoke anxiety, especially where punitive laws exist. Patients with HIV may
have fears associated with protecting others, which limit their interactions with other people and
lead to isolation. Referrals to a psychologist, social worker, specialized nurse, public health,
other interdisciplinary team member, or support groups can assist patients in coping with social
issues. Likewise, encouraging patients to share their HIV status with certain friends and family
can lead to practical and emotional benefits. Please see StatPearls' companion resources, "HIV
Antiretroviral Therapy," and "HIV Prevention," for more information.

Pearls and Other Issues

Clinicians must be aware of any rules and regulations regarding HIV screening, testing,
reporting, and managing HIV in the jurisdiction where they practice. These rules and regulations
vary widely. In some jurisdictions, rules and regulations may exist as public health acts and
follow a progressive enforcement framework; in others, they may be incorporated into criminal
law and carry significant penalties.

Relevant State Laws in the United States

Most states in the United States have defined guidelines in their administrative codes. For
example, Florida Administrative Code Rule 64B8-13.005 states that every physician licensee
must complete 1 hour of Category I American Medical Association CME that covers HIV and
AIDS every 2 years. This requirement includes information regarding Florida State Law for HIV
testing and test result reporting provided in statutes 381.004 and 384.25 mandating the
following:

Before HIV testing, the patient must be notified orally or in writing that the test is planned.
The patient must be given the right to refuse testing, which is documented in the medical
record.

If the patient or their legal guardian signs a medical consent form for medical care in a
healthcare setting, such as a clinic, emergency setting, or hospital, a separate consent form
for an HIV test during the period in which the general consent is in effect is not required.

In a nonhealthcare setting, such as community outreach programs, informed consent with

the option to decline testing and information regarding sites that provide anonymous
testing in the community must be obtained.

In the event of a positive test result, the patient must receive appropriate care and medical
support services, information on the importance of notifying partners who may have been
exposed, and ways to prevent transmission.

In the event of a negative test result, every effort should be made to notify the patient and
provide information regarding ways to prevent the acquisition of HIV.

In a healthcare setting, if the patient is discharged before the results are available, the
county health department must notify the test subject to fulfill the responsibility after a
positive test result.

Preliminary (unconfirmed) tests that yield positive results can be revealed only when
decisions about medical management cannot await confirmation, including the need to
provide recommendations to the person tested. Results can be revealed only to specific
people:

The person tested and clinicians responsible for the medical care and decision-
making for the tested individual.

The person tested and clinicians responsible for the care and decision-making of a
newborn who may be affected by these results.

Healthcare personnel subject to significant exposure from the person whose results
were positive.
 Individuals tested using rapid testing technologies under manufacturers' instructions
approved by the United States Food and Drug Administration.

Unconfirmed test results must not be presented to the patient as an HIV diagnosis. The
rationale for releasing unconfirmed results must be documented in the chart. Confirmatory
testing must be obtained, and the results must be communicated to the individual tested.

Positive HIV test results, after confirmatory testing, may only be released to the tested
individual or their designated legally authorized representative.

Results must be reported to the State Health Department following rules for reporting and
controlling disease. Results may also be shared with clinicians who use semen or body
parts from an infected individual, health facility committees for purposes of program
monitoring and evaluation, and authorized researchers and epidemiologists, as proscribed
under appropriate statutes and procedures.

The patient must provide written authorization for the release of such testing to any other
individual or third-party payor for HIV test results to be released. In this scenario, consent
beyond general consent is required to release medical records. A specific authorization for
the release of HIV test results must be provided.

If HIV testing is conducted due to medical personnel exposure, the occurrence should be
documented and recorded only in the medical personnel's personnel records. In addition,
the cost of the initial HIV test should be borne by the medical personnel or their employer.

If the source of the exposure is unavailable or not voluntarily present for testing, the
medical personnel or the employer may seek a court order for HIV testing from the source
individual. The test results should be released to the source and the person who
experienced the exposure.

Clinicians, laboratories, and healthcare facilities that diagnose or treat individuals with
HIV/AIDS must report the result no later than 2 weeks following the diagnosis or
treatment as outlined above.

Violation of these rules is subject to penalties, fines, and disciplinary actions.

Impact of Legislation on HIV Testing in the United States

Laws and regulations concerning HIV and AIDS are developed considering a variety of
parameters that impact patients' willingness to test for HIV. For example, to provide patients with
privacy, confidentiality, and dignity, the Florida legislature considered the need for informed
consent and privacy in designing laws regarding HIV and other sexually transmitted diseases,
including laws for reporting.

Informed consent

Informed consent includes an explanation to the patient regarding confidentiality,

mandatory reporting, and the opportunity for anonymous testing.

This consent maintains that in a healthcare setting, a patient must be notified of a planned
HIV test, and they have the right to refuse the test.

Informed consent allows a legal guardian to provide informed consent if a person is

incompetent, incapacitated, or a legal minor.

Confidentiality
 Confidentiality ensures information regarding a person's HIV status is kept confidential,
except when:

The patient gives consent.

The data are provided for statistical purposes and exclude identifying information.

The clinician or facility must disclose the result for mandatory reporting to medical
personnel, state agencies, or mandated court jurisdiction.

The information needs to be disclosed during a medical emergency; only relevant

information for the patient's care can be disclosed.

Consequences if confidentiality is violated include:

The person commits a misdemeanor of the first degree, which is punishable by a fine
of up to $1000 and up to 1 year in prison.

A person who spreads information about a patient with HIV or another sexually
transmitted disease for monetary gain or with malicious intent commits a felony in
the third degree, which is punishable by a fine of up to $5,000 or imprisonment of
up to 5 years.

Reporting

Reporting ensures results are promptly and confidentially reported to the Florida
Department of Health to allow for contact follow-up and other public health activities,
such as surveillance. A positive test result or other diagnosis of HIV or AIDS must be
reported within 2 weeks using the system developed by the CDC or an equivalent system
to ensure confidentiality.

The Department of Health may fine anyone who fails to report HIV or AIDS up to $500
for each offense, and a regulatory agency is informed of the violation.

Similar laws exist on these ethical principles in other settings worldwide, which are important to
reference when treating 1 or more patients with HIV.

Enhancing Healthcare Team Outcomes

Almost 21 million lives have been saved with antiretroviral therapy worldwide. However, current
prevention and treatment services miss or inadequately serve millions. Key indicators of the
quality of HIV care for optimal patient and population health outcomes include the linkage of
HIV-positive individuals to care, documentation of treatment by patients linked to care, and
attainment of viral suppression among patients who are treated. For example, in the United States
in 2021, 80% of patients with HIV were linked to care within 30 days of diagnosis, defined as at
least 1 viral load or CD4+ test. However, of all people with an HIV diagnosis in 2021, only 54%
were retained in care (defined as ≥2 viral loads or CD4+ tests ≥3 months apart in 2021), and only
66% were virally suppressed (defined as an HIV RNA level of <200 copies/mL).

Within countries, variability in key quality care indicators exists across

populations. Although the disparities are greatest in low- and middle-income countries,
significant inequities continue to exist in prevalence and incidence across population groups in
countries with well-developed HIV responses. For example, compared to the general population
in the United States, HIV disproportionately affects people who inject drugs, patients who live in
the United States South, and patients who are Black, Hispanic, Latino, transgender, or men
who have sex with men. Across the European Economic Area, migrants accounted for 44% of
new HIV diagnoses in 2019.
A successful HIV response depends on multiple factors, including utilizing a team-based and
patient-centered care approach, a focus on prevention in the community and healthcare
settings, robust monitoring and surveillance systems, continuous program quality improvement,
and supportive social and legal environments. An integrated interprofessional team including
physicians, nurses, pharmacists, social workers, public health officials, and community partners
is essential to improve clinical outcomes for patients with HIV, improve population health, and
ultimately change the course of the global HIV pandemic.[24]

Patient-Centered, Team-Based Care

Patient-centered care facilitates the maximum benefit from prevention services, improving
clinical and public health outcomes. As HIV is an epidemic that disproportionately affects
marginalized populations, programming that places the individual at the center of care ensures
equality, minimizes stigma, and overcomes socioeconomic barriers that limit care access. For
example, patients with HIV or who are at risk for HIV acquisition and have underlying
socioeconomic disadvantages or substance use disorders are at high risk for medical
nonadherence. Physicians, nurse practitioners, and physician assistants all provide primary care
to patients with HIV. Clinician use of current HIV guidelines, genotype resistance testing, and
measures to support adherence to therapy ensures patients receive adequate medical treatment.
Systematic monitoring for complications minimizes the risk and consequences of the disease and
ART.

Nurses are essential in achieving care and public health goals by supporting patients in
understanding, for example, the risk of transmission, complications, and the need for medication
adherence. Home-visiting nurses can help patients remain compliant with medical care and
laboratory testing. According to a study from sub-Saharan Africa, immediate ART at the time of
home-based positive test results increased clinical follow-up and linkage to care. Nurses and
nutritionists can monitor weight and promote adequate nutrition and hydration to promote overall
health, minimize cardiovascular risks, and minimize the risk of HIV wasting syndrome.

Pharmacists augment the patient's understanding by discussing potential adverse effects of

therapy, ways to minimize drug interactions, and ensuring patients know when to seek help
should any treatment complications occur. Measures such as blister-packed medications can ease
the burden of setting up pills, minimize the risk of incorrect dosing, and improve medication
adherence. Public health nurses and physicians are important in connecting and following up
with contacts to prevent further transmission. They have a primary role in preventing HIV in the
community, including identifying and responding rapidly to HIV outbreaks in the community.
They also support the patient care team in unusual instances where patients are persistently
unwilling or unable to follow recommendations to prevent transmission.

Community health, peer support, and social workers are vital in promoting patient well-being
and improving linkage to care. Social workers can allocate resources for transportation and
childcare support, provide assistance with mental health services, or make referrals to finance
medications. Community health and peer support workers, for example, assist in the
development of stigma-free services or increase the availability of home-based services. Please
see StatPearls' companion resource, "HIV Antiretroviral Therapy," for more information.[10]

Community HIV Prevention

Primordial, primary, and secondary prevention are all important in the context of improving
outcomes for HIV. The percentage of new transmissions and the number of HIV-positive people
who are aware of their HIV status are key quality indicators for prevention efforts. Worldwide,
86% of the 39 million people estimated to be living with HIV knew their status in 2022. In the
United States, 87% of the estimated 1.2 million people living with HIV knew their status in
2021. Primordial prevention includes addressing the determinants of health that lead to increased
risks for acquiring HIV, including poverty, discrimination, stigma, or other mechanisms
that marginalize groups of people. Beneficial social and policy environments are essential in
primordial prevention and the prevention and care spectrum.

Primary prevention targets patients who have risk factors, including public awareness and
education regarding safe sexual practices and ways to reduce the risk of HIV transmission among
people who inject drugs. The promotion of safer sexual practices, treatment of opioid use
disorder, and widespread access to clean syringe services and other harm reduction
approaches are effective prevention strategies that should be implemented across the globe.
[19] Voluntary medical circumcision for heterosexual males is an effective prevention approach
in southern and eastern areas of Africa where HIV is highly prevalent. Preexposure prophylaxis
is a highly effective strategy for patients at high risk, for example, due to a sexual partner who is
HIV positive, having multiple sexual partners without using condoms consistently, or the use of
injectable drugs.

Developing cost-effective recommendations and education to screen for HIV is a critical

component of prevention. For example, the United States Preventive Services Task Force
(USPSTF) recommends that clinicians in the United States screen all pregnant women and at-risk
persons aged 15 to 65, with particular emphasis on individuals at high risk of infection.
[20] Maternal HIV screening has resulted in a significant decline in mother-to-child HIV
transmission, preventing nearly 22,000 perinatal infections between 1994 and 2010.
[21] Treatment as prevention recognizes that HIV is not sexually transmitted if the viral load is
undetectable (defined as <200 copies of HIV-1 RNA/mL of plasma).[22][23] Otherwise known
as undetectable=utransmittable or U=U, evidence is increasing of the effectiveness for those who
share drug injection equipment. Emphasis on U=U is a strong motivator for patient adherence to
medication. However, with undetectable viral loads, HIV transmission occurs perinatally and
through breast milk. Please see StatPearls' companion resource, "Prevention of HIV," for more
information.

HIV Prevention in Healthcare Settings

In the healthcare context, the use of rigorous infection prevention and control procedures has led
to widespread decreases in occupationally and iatrogenically transmitted HIV. The elimination of
the reuse of needles, syringes, and other medical equipment that can transmit HIV has been a
global success story in many countries. The widespread implementation of standard precautions,
previously called universal precautions, is another key preventive strategy. Initially developed
to prevent HIV transmission, standard precautions are utilized to avoid the transmission of all
infectious agents. The first line of defense to break the chain of transmission of infectious agents
in healthcare settings is the application of standard precautions, irrespective of their known or
suspected infection status. The type of infection control practice necessary is based on the level
of anticipated contact with the patient and assumes that any patient's blood or body fluids may
contain an infectious agent.

Hand hygiene is the most important measure to prevent transmission of disease, encompassing
washing hands with soap and water for at least 40 to 60 seconds when visibly soiled, after
restroom use, or potential exposure to spore-forming organisms. Alcohol-based hand rubs can
otherwise be used. Clinicians should wash their hands between patients immediately after
gloves are removed and before and after any direct patient contact or contact with invasive
devices, blood or body fluids, secretions, mucous membranes, or nonintact skin if gloves are
worn. Gloves, masks, goggles, eye visors, face shields, or gowns are used when blood, body
fluids, secretions, or excretions could cause contamination. Needles and sharps should be
discarded immediately in appropriate puncture-resistant containers.

Occupational post-exposure prophylaxis is crucial for preventing infections in healthcare

settings, as it is challenging to avoid accidental exposures to potentially infectious body fluids.
Post-exposure prophylaxis involves the provision of a minimum of 3 antiretroviral drugs for 28
days for all occupational exposures to HIV after the exposure and within 72 hours. Counseling,
HIV testing at baseline and follow-up, and monitoring for toxicity are also provided. Using the
post-exposure prophylaxis consultation service for clinicians is recommended in all cases. Please
see StatPearls' companion resource, "Universal Precautions," for more information.[24][27]

Monitoring, Surveillance, and Continuous Quality Improvement

Collecting and using reliable, granular, and timely data are essential for improving team
performance and population health. Using data means identifying at-risk clients, setting targets,
and developing strategies. UNAIDS first proposed a set of global 90-90-90 HIV prevention
targets for HIV in 2014 by countries of the United Nations General Assembly. Although these
goals were not reached, many countries made significant progress. Setting 95-95-
95 goals for 2025, the goals were updated in 2020 and adopted by the United Nations General
Assembly in 2021 and include:

95% of all people with HIV who know their status

95% of all people who have HIV and receive antiretroviral therapy

95% of all patients on ART who achieve viral suppression

The projected impact is fewer than 370,000 people acquiring HIV and fewer than 250,000 people
dying from HIV worldwide in 2025. The WHO and country and state disease control and
prevention centers, such as the United States CDC, are primary data sources for monitoring HIV
trends and progress toward goals. Behavioral and clinical characteristics of adults with HIV
are followed in the United States by the Medical Monitoring Project. Instituted in 2005, this is a
cross-sectional, nationally representative, complex sample survey. The CDC's AtlasPlus
allows clinicians to explore national HIV, hepatitis, sexually transmitted infections,
and tuberculosis data relevant to their population.[CDC. NCCHHSTP AtlasPlus 2023.] All data
from 2020 and 2021 must be interpreted in the context of decreased case surveillance and
services during the COVID-19 pandemic. Consequently, clinicians can improve care and
contribute to population health improvements by completing required documentation,
participating in initiatives to streamline surveillance, and engaging in continuous program quality
improvement within their practice setting utilizing public health data.

Social and Policy Environments

Local legislative bodies, policy-making organizations, and institutions can improve patient-
centered care and population health outcomes for patients with HIV by basing legislative and
policy frameworks that influence the effectiveness of HIV and AIDS programming on
recommendations developed by organizations such as the UNAIDS, WHO, and the NIH. The
WHO recommends specific HIV policies that promote optimal HIV testing and care and
track any country's progression. These recommendations include the use of preexposure
prophylaxis, dual HIV and syphilis rapid diagnostic tests, self-testing, optimal first- and second-
line treatments, routine viral load testing, and same-day ART initiation, amongst other measures,
in national policies and guidelines. UNAIDS, WHO, and national HIV strategies
outline key social, legal, and policy factors that lead to better patient and population health
outcomes for HIV prevention and care.

Political commitment and adequate resources are fundamental building blocks for an
adequate public health response. The setting of targets can garner political commitment. The
United States National HIV/AIDS Strategy and the Ending the HIV Epidemic in the United
States initiative aims to reduce new HIV transmissions in the United States by 90% by 2030,
prioritizing the reduction of HIV-related health disparities and inequities and improving the well-
being of patients with HIV.[CDC. Ending the HIV epidemic 2023.] A renewed global
commitment to funding is necessary. The gap between actual and required funding is widening in
low- and middle-income countries, mainly due to a decrease in the proportion of funding
provided by high-income nations. Fully funded, resilient, integrated, and accessible public and
community health systems lead to increased uptake of both HIV and other health services. Social
and structural inequalities to HIV-related services, resources, and tools can be addressed through
universal health care, shared service delivery models, and measures to improve access to
medicines and health technologies for patients experiencing marginalization, including
uninsured or underinsured individuals in the United States.

The removal, or at a minimum, the nonenforcement of harmful laws must be a priority. For
example, laws criminalizing HIV exposure, non-disclosure, and transmission discourage people
from getting tested, increasing transmission and creating a barrier to early treatment. Likewise,
the criminalization of particular groups of people undermines an effective HIV response by
discouraging sex workers, men who have sex with men, and those who are transgender or inject
drugs from using prevention and treatment programs due to fear of arrest and prosecution. A
2015 study estimated that 33% to 46% of all new HIV cases over a decade could be avoided by
decriminalizing sex work worldwide.

Many countries have amended laws to remove barriers to the HIV response, including
decriminalizing vertical HIV transmission in Belize in 2023, sex work in Belgium in 2022, and
same-sex sexual relations in several countries in 2022 and 2023. However, concerning setbacks
occurred in many countries, including Indonesia. Strengthening laws, policies, and systems that
realize and protect human rights is also necessary. For example, the promotion of gender equity
and safe work environments leads to lower vulnerability for women and girls. Modeling studies
from Canada and Kenya show that the elimination of violence by police, clients, and strangers
could avert 17% to 20% of new HIV cases among women who are sex workers and their clients
in a decade.

Strengthened policies and laws augment the education and community action necessary
to address the stigma and discrimination that impact the health and well-being of patients with
HIV. According to UNAIDS, 1 in 3 countries reporting on HIV policies indicate that 10% of men
who have sex with men and more than 50% of sex workers, people who inject drugs, and
transgender individuals avoid healthcare due to fears of stigma, discrimination, or confidentiality.
Stigma and discrimination, rooted in outdated fears of HIV from the 1980s,
must be addressed through open discussion about HIV using non-stigmatizing language both
within and outside of health care. Discrimination can manifest in healthcare settings as the
refusal of service to patients with HIV, the use of stigmatizing language, or the absence of
appropriate services, resources, or tools.

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Disclosure: Helena Swinkels declares no relevant financial relationships with ineligible companies.

Disclosure: Angel Justiz Vaillant declares no relevant financial relationships with ineligible companies.

Disclosure: Andrew Nguyen declares no relevant financial relationships with ineligible companies.

Disclosure: Peter Gulick declares no relevant financial relationships with ineligible companies.

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