Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa.

BACKGROUND: Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa. METHODS: We enrolled adult participants in a cross-sectional study between May and September 2019. Eligible participants had a most recent documented viral load (VL) ≥ 1000 copies/mL after at least 6 months on ART. We genotyped HIV-1 reverse transcriptase and protease genes by Sanger sequencing and assessed ADR. We characterized the effect of ADR mutations on the predicted susceptibility to drugs used in combination with DTG. RESULTS: From 143 participants enrolled, we obtained sequence data for 115 (80%), and 92.2% (95% CI 85.7-96.4) had ADR. The proportion with ADR was similar for participants on first-line ART (65/70, 92.9%, 95% CI 84.1-97.6) and those on second-line ART (40/44, 90.9%, 95% CI 78.3-97.5), and was present for the single participant on third-line ART. Approximately 89% (62/70) of those on first-line ART had dual class NRTI and NNRTI resistance and only six (13.6%) of those on second-line ART had major PI mutations. Most participants (82%) with first-line viraemia maintained susceptibility to Zidovudine (AZT), and the majority of them had lost susceptibility to TDF (71%) and 3TC (84%). Approximately two in every five TDF-treated individuals had thymidine analogue mutations (TAMs). CONCLUSIONS: Susceptibility to AZT among most participants with first-line viraemia suggests that a new second-line regimen of AZT + 3TC + DTG could be effective. However, atypical occurrence of TAMs in TDF-treated individuals suggests a less effective AZT + 3TC + DTG regimen in a subpopulation of patients. As most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemia before switch to TDF + 3TC + DTG is important to avoid DTG functional monotherapy. These findings highlight a need for close monitoring of outcomes on new standardized treatment regimens.

Progress towards the UNAIDS 90-90-90 goals by age and gender in a rural area of KwaZulu-Natal, South Africa: a household-based community cross-sectional survey.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has developed an ambitious strategy to end the AIDS epidemic. After eight years of antiretroviral therapy (ART) program we assessed progress towards the UNAIDS 90-90-90 targets in Mbongolwane and Eshowe, KwaZulu-Natal, South Africa. METHODS: We conducted a cross-sectional household-based community survey using a two-stage stratified cluster probability sampling strategy. Persons aged 15-59 years were eligible. We used face-to-face interviewer-administered questionnaires to collect information on history of HIV testing and care. Rapid HIV testing was performed on site and venous blood specimens collected from HIV-positive participants for antiretroviral drug presence test, CD4 count and viral load. At the time of the survey the CD4 threshold for ART initiation was 350 cells/µL. We calculated progression towards the 90-90-90 UNAIDS targets by estimating three proportions: HIV positive individuals who knew their status (first 90), those diagnosed who were on ART (second 90), and those on ART who were virally suppressed (third 90). RESULTS: We included 5649/6688 (84.5%) individuals. Median age was 26 years (IQR: 19-40), 62.3% were women. HIV prevalence was 25.2% (95% CI: 23.6-26.9): 30.9% (95% CI: 29.0-32.9) in women; 15.9% (95% CI: 14.0-18.0) in men. Overall progress towards the 90-90-90 targets was as follows: 76.4% (95% CI: 74.1-78.6) knew their status, 69.9% (95% CI: 67.0-72.7) of those who knew their status were on ART and 93.1% (95% CI: 91.0-94.8) of those on ART were virally suppressed. By sex, progress towards the 90-90-90 targets was: 79%-71%-93% among women; and 68%-68%-92% among men (p-values of women and men comparisons were < 0.001, 0.443 and 0.584 respectively). By age, progress was: 83%-75%-95% among individuals aged 30-59 years and 64%-58%-89% among those aged 15-29 years (p-values of age groups comparisons were < 0.001, < 0.001 and 0.011 respectively). CONCLUSIONS: In this context of high HIV prevalence, significant progress has been achieved with regards to reaching the UNAIDS 90-90-90 targets. The third 90, viral suppression in people on ART, was achieved among women and men. However, gaps persist in HIV diagnosis and ART coverage particularly in men and individuals younger than 30 years. Achieving 90-90-90 is feasible but requires additional investment to reach youth and men.