Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, northern Tanzania

Drug resistance is a public health concern. Profiles of HIV drug resistance mutations (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-line HIV drugs in Moshi, northern Tanzania. A case-control study was conducted at KCMC, Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics in Moshi from October, 2017 to August, 2018. Cases and controls were HIV-infected individuals with VF and viral suppression (VS) respectively. HIV-1 reverse transcriptase and protease genes were amplified and sequenced. Stanford Universitys HIV drug resistance database and REGA HIV-1 Subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. Odds ratios with 95% confidence intervals investigated predictors of VF. P-value <5% was considered statistically significant. A total of 124 participants were recruited, of whom 63 (50.8%) had VF and 61 (49.2%) had VS. Majority (66.1%) were females. Median [IQR] age and duration on ART were 45 [35-52] years and 72 [48-104] months respectively. Twenty five out of 26 selected HIV-1 RNA samples from cases were successively sequenced. Twenty four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with non-nucleoside reverse transcriptase inhibitor (NNRTI) associated mutations as the majority (92%). Frequent NNRTI resistance mutations were K103N (n=11), V106M (n=5) and G190A (n=5). Prevalent nucleoside reverse transcriptase inhibitors mutations were M184V (n=17), K70R (n=7) and D67N (n=6). Dual-class resistance was observed in 16 (64%) samples. Thirteen samples (52%) had at least one thymidine analogue-associated resistance mutation (TAM). Three samples (12%) had T69D mutation with at least 1 TAM. Age was independently associated with VF [aOR 0.94 (0.90-0.97) p<0.001]. In conclusion, HIV drug resistance is common among people failing antiretroviral therapy and resistance testing will help to guide switching of HIV drugs.