Emergence of HIV drug resistance poses a serious risk of inactivity to all currently approved antiretroviral drugs. 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 Kilimanjaro Christian Medical Centre, Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics 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 University’s HIV drug resistance database and REGA subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. Odds ratios (OR) with 95% confidence interval (95% CI) 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, 61 (49.2%) had VS and 82 (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 samples from cases were successfully sequenced. Twenty-four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with non-nucleoside analogue reverse transcriptase inhibitor (NNRTI)-resistance associated mutations as the majority (92%). Frequent NNRTI-resistance associated mutations were K103N (n = 11), V106M (n = 5) and G190A (n = 5). Prevalent nucleoside analogue reverse transcriptase inhibitors-resistance associated 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-resistance associated mutation (TAM). Three samples (12%) had T69D mutation with at least 1 TAM. Two samples (8%) had at least one mutation associated with protease inhibitor resistance. Age [aOR = 0.94, 95% CI (0.90–0.97), p < 0.001] and occupation [aOR = 0.35, 95% CI (0.12–1.04), p = 0.059] associated with VF. In conclusion, HIV drug resistance is common among people failing antiretroviral therapy. Resistance testing will help to guide switching of HIV drugs.
28Drug resistance is a public health concern. Profiles of HIV drug resistance mutations 29 (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study 30 aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-31 line HIV drugs in Moshi, northern Tanzania. A case-control study was conducted at KCMC, 32 Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics in Moshi 33 from October, 2017 to August, 2018. Cases and controls were HIV-infected individuals with 34 VF and viral suppression (VS) respectively. HIV-1 reverse transcriptase and protease genes 35 were amplified and sequenced. Stanford University's HIV drug resistance database and 36 REGA HIV-1 Subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. 37 Odds ratios with 95% confidence intervals investigated predictors of VF. P-value <5% was 38 considered statistically significant. A total of 124 participants were recruited, of whom 63 39 (50.8%) had VF and 61 (49.2%) had VS. Majority (66.1%) were females. Median [IQR] age 40 and duration on ART were 45 [35-52] years and 72 [48-104] months respectively. Twenty 41 five out of 26 selected HIV-1 RNA samples from cases were successively sequenced. Twenty 42 four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with 43 non-nucleoside reverse transcriptase inhibitor (NNRTI) associated mutations as the majority 44 (92%). Frequent NNRTI resistance mutations were K103N (n=11), V106M (n=5) and G190A 45 (n=5). Prevalent nucleoside reverse transcriptase inhibitors mutations were M184V (n=17), 46 K70R (n=7) and D67N (n=6). Dual-class resistance was observed in 16 (64%) samples.47
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