Abstract
The South African national combination antiretroviral therapy (cART) roll-out program started in 2006, with over 4.4 million people accessing treatment since it was first introduced. HIV-1 drug resistance can hamper the success of cART. This study determined the patterns of HIV-1 drug-resistance associated mutations (RAMs) in People Living with HIV-1 (PLHIV-1). Receiving first (for children below 3 years of age) and second-line (for adults) cART regimens in South Africa. During 2017 and 2018, 110 patients plasma samples were selected, 96 samples including those of 17 children and infants were successfully analyzed. All patients were receiving a boosted protease inhibitor (bPI) as part of their cART regimen. The viral sequences were analyzed for RAMs through genotypic resistance testing. We performed genotypic resistance testing (GRT) for Protease inhibitors (PIs), Reverse transcriptase inhibitors (RTIs) and Integrase strand transfer inhibitors (InSTIs). Viral sequences were subtyped using REGAv3 and COMET. Based on the PR/RT sequences, HIV-1 subtypes were classified as 95 (99%) HIV-1 subtype C (HIV-1C) while one sample as 02_AG. Integrase sequencing was successful for 89 sequences, and all the sequences were classified as HIV-1C (99%, 88/89) except one sequence classified CRF02_AG, as observed in PR/RT. Of the 96 PR/RT sequences analyzed, M184V/I (52/96; 54%) had the most frequent RAM nucleoside reverse transcriptase inhibitor (NRTI). The most frequent non-nucleoside reverse transcriptase inhibitor (NNRTI) RAM was K103N/S (40/96, 42%). Protease inhibitor (PI) RAMs M46I and V82A were present in 12 (13%) of the sequences analyzed. Among the InSTI major RAM two (2.2%) sequences have Y143R and T97A mutations while one sample had T66I. The accessory RAM E157Q was identified in two (2.2%). The data indicates that the majority of the patients failed on bPIs didn’t have any mutation; therefore adherence could be major issue in these groups of individuals. We propose continued viral load monitoring for better management of infected PLHIV.
Highlights
MATERIALS AND METHODSExceptional improvements in combination antiretroviral therapy regimens have changed HIV/AIDS from a deadly pandemic to a chronic and manageable disease (Trickey et al, 2017). cART has made significant contributions to reducing the rates of morbidity and mortality in people living with HIV (PLHIV) and has led to better management of infection at an individual level, in high-income countries and in low- and middle-income countries (Hightower et al, 2011; UNAIDS, 2017)
In accordance with the World Health Organization’s (WHO) guidelines, the recommended first-line cART in South Africa consists of a non-nucleoside reverse transcriptase inhibitor (NNRTI) backboned regimen of efavirenz (EFV), combined with two nucleoside reverse transcriptase inhibitors (NRTIs), namely lamivudine (3TC) and either tenofovir disoproxil fumarate (TDF), for adults, or abacavir (ABC), for children
We aimed to identify the pattern of acquired drug resistance mutations (DRMs) among PLHIV in South Africa receiving boosted PI- (bPI) second-line cART
Summary
MATERIALS AND METHODSExceptional improvements in combination antiretroviral therapy (cART) regimens have changed HIV/AIDS from a deadly pandemic to a chronic and manageable disease (Trickey et al, 2017). cART has made significant contributions to reducing the rates of morbidity and mortality in people living with HIV (PLHIV) and has led to better management of infection at an individual level, in high-income countries and in low- and middle-income countries (Hightower et al, 2011; UNAIDS, 2017). South Africa’s national HIV cART program was introduced in 2006, with a public health approach (UNAIDS, 2018). In accordance with the World Health Organization’s (WHO) guidelines, the recommended first-line cART in South Africa consists of a non-nucleoside reverse transcriptase inhibitor (NNRTI) backboned regimen of efavirenz (EFV), combined with two nucleoside reverse transcriptase inhibitors (NRTIs), namely lamivudine (3TC) and either tenofovir disoproxil fumarate (TDF), for adults, or abacavir (ABC), for children. The WHO guidelines recommend the PI lopinavir co-formulated with ritonavir (lopinavir/ritonavir [LPV/r]) in a four-to-one ratio in first-line cART for children younger than 3 years, based on its superiority when compared with nevirapine (NVP), regardless of previous NVP exposure to prevent mother-to-child HIV transmission (Meintjes et al, 2017)
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