High viral suppression and detection of dolutegravir-resistance associated mutations in treatment-experienced Tanzanian adults living with HIV-1 in Dar es Salaam

Abstract

To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam. Patients with unsuppresed viral loads (local criteria viral load (VL) ≥ 1000 copies/mL) were tested for HIVDR mutations using the WHO adapted protocol for plasma samples. Mutations were interpreted using the Stanford HIVDR database. In total 600 individuals participated in this survey, the majority were female (76.83%), mean age ($$\pm$$ ± standard deviation) was 44.0 ($$\pm$$ ± 11.6) years. The median duration on ART (interquartile range) was 6.5 (3.9–10.2) years. Approximately 99% were receiving tenofovir + lamivudine + dolutegravir as a fixed dose combination. VL testing was successful in 99.67% (598/600) of survey patients and only 33 had VL ≥ 1000 copies/mL, resulting in a viral suppression level of 94.48% (565/598, 95% CI 92.34–96.17%). For 23 samples, protease and reverse transcriptase (RT) genotyping were successful, with 13 sequences containing RT inhibitor surveillance drug resistance mutations (SDRMs) (56.5%). No SDRM against protease inhibitors were detected. Thirty samples were successfully genotyped for integrase with 3 sequences (10.08%) containing integrase strand transfer inhibitor (INSTI) SDRMs. In samples successfully genotyped in the three genetic regions, 68.18% (16/22) had a genotypic susceptibility score (GSS) ≥ 2.5 for the concurrent regimen, implying factors beyond drug resistance caused the unsuppressed viral load. For five patients, GSS indicated that HIVDR may have caused the unsuppressed viral load. All three patients with INSTI resistance mutations were highly resistant to dolutegravir and accumulated nucleoside and non-nucleoside RT inhibitor HIVDR mutations. Although in this cohort the last 95 UNAIDS target was almost achieved, HIVDR mutations, including INSTIs resistance mutations were detected in HIV-positive individuals taking ART for at least one year. We recommend the design and implementation of high-impact interventions to prevent the increase of HIVDR, failure of dolutegravir and address the non-resistance factors in the study area.

Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review

“…In a study from Nigeria, GRT was performed on 33 samples from 281 individuals with VF [ 71 ]. In three studies from Tanzania, GRT was performed in nearly all of the 181 individuals with VF [ 72 , 73 , 74 ]. Among the estimated 214 individuals in these five studies undergoing GRT, 19 (8.9%) developed an INSTI DRM—most commonly G118R and R263K.…”

“…We described six such studies including one from Brazil of 113 PLWH with confirmed VF on a first-line regimen of DTG plus two NRTIs [ 42 ] and five from Sub-Saharan Africa. The studies from Sub-Saharan Africa included approximately 214 individuals, most of whom had prior ART experience before initiating DTG treatment [ 70 , 71 , 72 , 73 , 74 ]. The study from Brazil found that approximately six percent of the samples tested were found to have INSTI DRMs, whereas in the studies from Sub-Saharan Africa, approximately nine percent of the samples tested had INSTI DRMs.…”

Prevalence and factors associated with viral non‐suppression in people living with HIV receiving antiretroviral therapy in sub‐Saharan Africa: A systematic review and meta‐analysis

“…be highly effective and tolerable as compared to efavirenz-based regimen. 14,16,55,56 Being male was associated with increased odds of having VNS, suggesting potential gender-related disparities in VNS. The high rates of VNS among males compared to females in some contexts could be attributed to societal expectations around masculinity that often discourage men from seeking healthcare 57…”

Risk of Emergent Dolutegravir Resistance Mutations In People Living With HIV: A Rapid Scoping Review

“…In a study from Nigeria, GRT was performed on 33 samples from 281 individuals with VF [73]. In three studies from Tanzania, GRT was performed in nearly all of the 181 individuals with VF [74][75][76]. Among the estimated 214 individuals in these five studies undergoing GRT, 19 (8.9%) developed an INSTI DRM -most commonly G118R and R263K.…”

“…We described six such studies including one from Brazil of 113 PLWH with confirmed VF on a first-line regimen of DTG plus two NRTIs [42] and five from Sub-Saharan Africa. The studies from Sub-Saharan Africa included approximately 214 individuals most of whom had prior ART experience before initiating DTG treatment [72][73][74][75][76]. The study from Brazil found that approximately six percent of the samples tested were found to have INSTI DRMs while in the studies from Sub-Saharan Africa, approximately nine percent of the samples tested had INSTI DRMs.…”