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

Abstract

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.

Prevalence, predictors and geospatial patterns of HIV drug resistance in South Africa: Insights from the 2017 national HIV household survey

“…Despite that, all provinces and locality types had HIVDR levels above 20%, ranging between 21.6% and 36.6% on provincial level and from Our study found that after adjusting for potential confounders, the ARV-exposed had higher odds of HIVDR compared to the ARV-negative PLHIV. Consistent with our ndings, a national survey in Rwanda also found that ART regimens were signi cantly associated with HIVDR [43]. In contrast, a Nigerian national survey observed a signi cant association between HIVDR and being ARV-negative [28].…”

“…In addition, the 25-34 years old and ≥ 45 years old age groups had reduced odds of developing HIVDR compared to 15-24 years old age group. On the contrary, national surveys from Rwanda, Kenya, Tanzania, Uganda and Nigeria found no signi cant association between HIVDR and age [28,43]. In a Chinese study by Zhou et al [44], being ≥ 15 years old signi cantly predisposed individuals to higher odds of HIVDR.…”

“…A Chinese study from a province with the highest burden of HIV also found non-signi cant association between HIVDR and sex or ethnicity [44]. In addition, national surveys from Kenya, Uganda, Tanzania, Nigeria and Rwanda also found no signi cant association between HIVDR and sex [28,43]. On the contrary, the national Italian study found that male gender was signi cantly associated with HIVDR [45].…”

Clinical outcomes after viraemia among people receiving dolutegravir versus efavirenz-based first-line antiretroviral therapy in South Africa

“…In South Africa, about 23% of people living with HIV (PLHIV) experience an episode of viraemia during first-line antiretroviral therapy (ART) [1]. Persistent viraemia during ART in PLHIV is usually due to inconsistent adherence [2,3] or drug resistance [3][4][5] and increases the risk of virologic or treatment failure [6,7]. This often leads to a slower immune reconstitution [8] and a higher incidence of all-cause mortality [9][10][11].…”