Background
In sub-Saharan Africa (SSA), rates of HIV drug resistance (HIVDR) among patients with antiretroviral treatment (ART) failure are high for non-nucleoside reverse transcriptase inhibitors (NNRTIs), with implications for the risk of HIV mother-to-child transmission among pregnant women. Since 2019, the WHO recommends dolutegravir (DTG), an integrase strand transfer inhibitor (INSTI), in first-line regimens due to its high barrier to resistance. We aimed to describe HIVDR mutations among pregnant women living in SSA at the time of DTG scale-up.
Methods
This observational study is nested in a malaria prevention clinical trial among pregnant women with HIV conducted between 2019 and 2023 in Gabon and Mozambique. Available samples from women with virological failure (HIV viral load >400 copies/mL) at the first antenatal care (ANC) visit were analysed for HIVDR mutations using Illumina MiSeq®. Drug susceptibility was predicted using the Stanford HIVdb scoring system. Characteristics of participants were compared by the presence of HIVDR.
Results
A total of 99 women contributed to this study and 39 had at least one HIVDR mutation at their first ANC visit. Participant’s median age was 25 years [IQR 22-31], which was higher in women with HIVDR mutations compared to those without (29 vs 24 years; p=0.009). At the time of the first ANC visit, 38 (38.4%) women were on ART, with a higher proportion in the group with HIVDR mutations compared to the group without (64.1% vs 21.7%; p<0.001). NNRTI mutations were detected in 36 (36.4%) women and INSTI mutations in 6 (6.1%) women. In one ART-experienced but INSTI-naïve participant two INSTI mutations, H51Y and R263K (at frequencies of 17.8% and 99.8% respectively), were detected, indicating intermediate resistance to DTG. Another participant receiving a DTG-based regimen had a high-level resistance mutation, G118R, which is associated with a 5-10-fold reduced susceptibility to DTG.
Conclusions
The prevalence of INSTI mutations was low in the early phases of DTG scale-up. Nonetheless, a mutation against DTG was detected in an INSTI-naïve pregnant woman from Mozambique. This finding calls for continued surveillance of HIV drug resistance in vulnerable and high-risk populations from SSA.
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