Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: A cross-sectional nationally representative survey.

BACKGROUND: We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda. METHODS: This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE. RESULTS: Median time on ART was 86.4 months (interquartile range [IQR], 44.8-130.2 months), and median CD4 count at ART initiation was 311 cells/mm3 (IQR, 197-484 cells/mm3). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022-10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028-0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016-0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084-0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198-5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005). CONCLUSION: The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.

HIV-1 Recent Infection Testing Algorithm With Antiretroviral Drug Detection to Improve Accuracy of Incidence Estimates.

BACKGROUND: HIV-1 incidence calculation currently includes recency classification by HIV-1 incidence assay and unsuppressed viral load (VL ≥ 1000 copies/mL) in a recent infection testing algorithm (RITA). However, persons with recent classification not virally suppressed and taking antiretroviral (ARV) medication may be misclassified. SETTING: We used data from 13 African household surveys to describe the impact of an ARV-adjusted RITA on HIV-1 incidence estimates. METHODS: HIV-seropositive samples were tested for recency using the HIV-1 Limiting Antigen (LAg)-Avidity enzyme immunoassay, HIV-1 viral load, ARVs used in each country, and ARV drug resistance. LAg-recent result was defined as normalized optical density values ≤1.5. We compared HIV-1 incidence estimates using 2 RITA: RITA1: LAg-recent + VL ≥ 1000 copies/mL and RITA2: RITA1 + undetectable ARV. We explored RITA2 with self-reported ARV use and with clinical history. RESULTS: Overall, 357 adult HIV-positive participants were classified as having recent infection with RITA1. RITA2 reclassified 55 (15.4%) persons with detectable ARV as having long-term infection. Those with detectable ARV were significantly more likely to be aware of their HIV-positive status (84% vs. 10%) and had higher levels of drug resistance (74% vs. 26%) than those without detectable ARV. RITA2 incidence was lower than RITA1 incidence (range, 0%-30% decrease), resulting in decreased estimated new infections from 390,000 to 341,000 across the 13 countries. Incidence estimates were similar using detectable or self-reported ARV (R2 > 0.995). CONCLUSIONS: Including ARV in RITA2 improved the accuracy of HIV-1 incidence estimates by removing participants with likely long-term HIV infection.