Treatment Emergent Dolutegravir Resistance Mutations in Individuals Naïve to HIV-1 Integrase Inhibitors: A Rapid Scoping Review
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Search Results
3.2. Reports of Emergent INSTI-Associated DRMs
3.3. Phenotypic Impact of DTG-Selected INSTI-Associated DRMs
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Author (Year) 1 | Countries | Population 2 | ART Hx | VL Status | ART Regimen 3 | # with DRMs |
---|---|---|---|---|---|---|
Blanco (2018) [13] | Spain | Trial | Experienced | VS | DTG | 2 |
Cahn (2013) [9] | Multinational | Trial | Experienced | Viremic | DTG + OBR | 5 |
Chinula (2023) [39] | Multinational | Trial | Naïve | Viremic | DTG + 2 NRTIs | 1 |
Hocqueloux (2019) [20] | France | Trial | Experienced | VS | DTG | 2 |
Paton (2022) [29] | Sub-Saharan Africa | Trial | Experienced | Viremic | DTG + 2 NRTIs | 9 |
Taiwo (2018) [18] | U.S. | Trial | Naïve | Viremic | DTG + 3TC | 1 |
Turkova (2021) [25] | Multinational | Trial | Experienced | Viremic | DTG + 2 NRTIs | 4 |
Underwood (2022) [32] | Multinational | Trial | First-line VF | Viremic | DTG + 2 NRTIs | 6 |
Vavro (2022) [35] | U.S. | Trial | Experienced | Viremic | DTG + 2 NRTIs | 6 |
Wijting (2017) [12] | Netherlands | Trial | Experienced | VS | DTG | 4 |
Abdullah (2023) [36] | Nigeria | Cohort | Experienced | Viremic | DTG + 2 NRTIs | 1 |
Khamadi (2023) [42] | Tanzania | Cohort | Experienced | Viremic | DTG + 2 NRTIs | 3 |
Oldenbuettel (2017) [11] | Germany | Cohort | Experienced | VS | DTG | 1 |
Bowman (2023) [38] | U.K. | Cohort | Experienced | VS | DTG + 3TC | 1 |
Palmier (2023) [44] | Spain | Cohort | Experienced | VS | DTG + 3TC | 1 |
Armenia (2023) [37] | Italy, France | Case Series | Naïve, Experienced | Viremic, VS | Multiple | 9 |
Diaz (2023) [40] | Brazil | Case Series | Naïve | Viremic | DTG + 2 NRTIs | 4 |
Frange (2021) [23] | France | Case Series | Experienced | Viremic | DTG + 2 NRTIs | 1 |
Gil (2022) [27] | Spain | Case Series | Naïve, Experienced | Not reported | DTG + 2 NRTIs | 5 |
Kamori (2023) [41] | Tanzania | Case Series | Experienced | Viremic | DTG + 2 NRTIs | 3 |
Lepik (2017) [10] | Canada | Case Series | Naïve, Experienced | Viremic | DTG + 2 NRTIs | 3 |
Schramm (2022) [31] | Malawi | Case Series | Experienced | Viremic | DTG + 2 NRTIs | 2 |
Seatla (2021) [24] | Botswana | Case Series | Experienced | Viremic | DTG + 2 NRTIs | 3 |
Van Oosterhout (2022) [34] | Malawi | Case Series | Naïve, Experienced | Viremic, Not reported | DTG + 2 NRTIs | 8 |
Ahmed (2019) [19] | East Africa | Case Report(s) | Experienced | Viremic | DTG + DRV | 1 |
Botha (2022) [26] | South Africa | Case Report(s) | Experienced | Viremic | DTG + 2 NRTIs | 1 |
Cardoso (2018) [14] | Portugal | Case Report(s) | Experienced | Viremic | DTG + 2 NRTIs | 2 |
Cochrane (2018) [15] | U.K. | Case Report(s) | Experienced | Viremic | DTG + 2 NRTIs | 1 |
Fulcher (2018) [16] | U.S. | Case Report(s) | Naïve | Viremic | DTG + 2 NRTIs | 1 |
Lubke (2019) [21] | Germany | Case Report(s) | Naïve | Viremic | DTG + 2 NRTIs | 1 |
M. Chirimuta (2022) [28] | Zimbabwe | Case Report(s) | Experienced | VS, Not reported | DTG + 2 NRTIs | 2 |
Mahomed (2020) [22] | South Africa | Case Report(s) | Experienced | Viremic | DTG + 2 NRTIs | 1 |
Malinga (2023) [43] | South Africa | Case Report(s) | Experienced | Viremic | DTG + 2 NRTIs | 1 |
Pena Lopez (2018) [17] | Spain | Case Report(s) | Naïve | Viremic | DTG + 2 NRTIs | 1 |
Revollo (2022) [30] | Spain | Case Report(s) | Experienced | VS | DTG + 3TC | 1 |
van Kampen (2022) [33] | Netherlands | Case Report(s) | Experienced | Viremic | DTG + 2 NRTIs | 1 |
ART History | VL Status | ART Regimen | # with DRMs |
---|---|---|---|
Naïve | Viremic | DTG + 2 NRTIs | 13 |
Naïve | Viremic | DTG + 3TC | 2 |
Experienced | Viremic | DTG + 2 NRTIs | 49 |
Experienced | Viremic | DTG + OBR | 5 |
Experienced | Viremic | DTG + b/DRV | 1 |
Experienced | VS | DTG | 11 |
Experienced | VS | DTG + 2 NRTIs | 4 |
Experienced | VS | DTG + 3TC | 3 |
Experienced | VS | DTG + RPV | 1 |
Experienced | Uncertain | DTG + 2 NRTIs | 9 |
Experienced | Uncertain | DTG + 3TC | 1 |
DRM A | DRM B | A and B | A Alone | B Alone | Neither | Spearman Rho | p Value |
---|---|---|---|---|---|---|---|
Positively correlated DRMs 2 | |||||||
G140S | Q148H | 3 | 1 | 0 | 95 | 0.86 | <0.001 |
G140A | Q148K | 2 | 2 | 2 | 93 | 0.48 | <0.001 |
G140A | Q148R | 2 | 2 | 3 | 92 | 0.42 | <0.001 |
T66A | G118R | 5 | 0 | 23 | 70 | 0.37 | <0.001 |
S147G | N155H | 4 | 4 | 9 | 82 | 0.32 | 0.001 |
E157Q | R263K | 7 | 0 | 40 | 52 | 0.29 | 0.004 |
S147G | Q148R | 2 | 6 | 3 | 88 | 0.27 | 0.007 |
G118R | E138K | 8 | 17 | 8 | 62 | 0.24 | 0.02 |
L74M | G118R | 2 | 0 | 25 | 70 | 0.23 | 0.02 |
G140S | N155H | 2 | 2 | 11 | 84 | 0.22 | 0.03 |
T97A | N155H | 2 | 2 | 11 | 84 | 0.22 | 0.03 |
A49G | R263K | 4 | 0 | 43 | 52 | 0.22 | 0.03 |
L74I | G118R | 3 | 1 | 25 | 69 | 0.21 | 0.04 |
Negatively correlated DRMs 3 | |||||||
G118R | R263K | 3 | 24 | 42 | 28 | −0.44 | <0.001 |
E138K | R263K | 2 | 16 | 43 | 36 | −0.34 | <0.001 |
Q148KRH | R263K | 0 | 11 | 46 | 41 | −0.33 | <0.001 |
N155H | R263K | 2 | 11 | 45 | 41 | −0.25 | 0.01 |
G118R | N155H | 0 | 29 | 13 | 57 | −0.25 | 0.01 |
T66I | R263K | 0 | 6 | 47 | 46 | −0.24 | 0.02 |
G118R | Q148KRH | 0 | 28 | 11 | 59 | −0.23 | 0.03 |
Signature DRM | # Additional DRMs | # Results | Median Fold Reduced Susceptibility | IQR | Range |
---|---|---|---|---|---|
G118R | 0 | 2 | 18.8 | 14–23 | 9.6–28 |
1 | 7 | 22 | 11–29 | 7.2–30 | |
≥2 | 5 | 16 | 13–22 | 8.0–52 | |
R263K | 0 | 7 | 2.0 | 1.8–2.2 | 1.5–3.3 |
1 | 5 | 2.1 | 1.7–4.2 | 1.3–7.0 | |
≥2 | 1 | 6.3 | 6.3 | 6.3 | |
N155H | 0 | 8 | 1.4 | 1.2–1.6 | 1.1–2.1 |
1 | 14 | 1.7 | 1.5–2.0 | 1.1–3.5 | |
≥2 | 8 | 3.1 | 1.9–24 | 1.5–68 | |
Q148H/R/K | 0 | 11 | 0.8 | 0.7–1.1 | 0.4–1.6 |
1 | 44 | 3.4 | 1.9–5.5 | 0.5–17 | |
≥2 | 27 | 8.8 | 3.5–15 | 0.6–186 |
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Tao, K.; Rhee, S.-Y.; Chu, C.; Avalos, A.; Ahluwalia, A.K.; Gupta, R.K.; Jordan, M.R.; Shafer, R.W. Treatment Emergent Dolutegravir Resistance Mutations in Individuals Naïve to HIV-1 Integrase Inhibitors: A Rapid Scoping Review. Viruses 2023, 15, 1932. https://doi.org/10.3390/v15091932
Tao K, Rhee S-Y, Chu C, Avalos A, Ahluwalia AK, Gupta RK, Jordan MR, Shafer RW. Treatment Emergent Dolutegravir Resistance Mutations in Individuals Naïve to HIV-1 Integrase Inhibitors: A Rapid Scoping Review. Viruses. 2023; 15(9):1932. https://doi.org/10.3390/v15091932
Chicago/Turabian StyleTao, Kaiming, Soo-Yon Rhee, Carolyn Chu, Ava Avalos, Amrit K. Ahluwalia, Ravindra K. Gupta, Michael R. Jordan, and Robert W. Shafer. 2023. "Treatment Emergent Dolutegravir Resistance Mutations in Individuals Naïve to HIV-1 Integrase Inhibitors: A Rapid Scoping Review" Viruses 15, no. 9: 1932. https://doi.org/10.3390/v15091932