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

Author:

Musengimana Gentille12ORCID,Tuyishime Elysee2,Kiromera Athanase3,Malamba Samuel S.2,Mulindabigwi Augustin1,Habimana Madjid R.1,Baribwira Cyprien3,Ribakare Muhayimpundu1,Habimana Savio D.1,DeVos Josh4ORCID,Mwesigwa Richard C. N.2,Kayirangwa Eugenie2,Semuhore Jules M.5,Rwibasira Gallican N.1,Suthar Amitabh B.4,Remera Eric167

Affiliation:

1. Ministry of Health, Rwanda Biomedical Center, HIV/AIDs, STIs and OBBI Division, Kigali City, Rwanda

2. U.S. Centers for Disease Control and Prevention, Center for Global Health, Division of Global HIV & TB, Rwanda

3. University of Maryland, Center for International Health, Education and Biosecurity, (CIHEB), Baltimore, MD USA

4. U.S. Centers for Disease Control and Prevention, Center for Global Health, Division of Global HIV & TB, Atlanta, GA USA

5. World Health Organization, Rwanda Office

6. University of Basel, Basel, Switzerland

7. Swiss Tropical and Public Health Institute, Basel, Switzerland

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.

Funder

The President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention

Publisher

SAGE Publications

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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