Browsing by Author "Ikomey, George Mondinde"
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Item Analyses of HIV-1 integrase sequences prior to South African national HIV-treatment program and available of integrase inhibitors in Cape Town, South Africa(Nature Publishing Group, 2018) Brado, Dominik; Obasa, Adetayo Emmanuel; Ikomey, George Mondinde; Cloete, Ruben; Singh, Kamalendra; Engelbrecht, Susan; Neogi, Ujjwal; Jacobs, Graeme BrendonHIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatmentnaive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2.85% (9/314) in database derived sequences. RAMs were present at IN-positions 66, 92, 143, 147 and 148, all of which may confer resistance to Raltegravir (RAL) and Elvitegravir (EVG), but are unlikely to affect second-generation Dolutegravir (DTG), except mutations in the Q148 pathway. Furthermore, protein modeling showed, naturally occurring polymorphisms impact the stability of the intasome-complex and therefore may contribute to an overall potency against InSTIs. Our data suggest the prevalence of InSTI RAMs, against InSTIs, is low in South Africa, but natural polymorphisms and subtype-specific differences may influence the effect of individual treatment regimens.Item HIV-1 diversity and the implementation of integrase strand-transfer inhibitors as part of combination antiretroviral therapy(SAMA, 2020) Cloete, Ruben; Mikasi, Sello Given; Ikomey, George Mondinde: The integrase (IN) strand-transfer inhibitor (InSTI) dolutegravir (DTG) is now recommended by the World Health Organization as part of salvage and/or first-line combination antiretroviral therapy (cART).[1] DTG has a high genetic barrier against developing resistance and is effective against all strains that previously exhibited resistance-associated mutations (RAMs) against other cART regimens.[2] Recommendations to use DTG were delayed owing to preliminary findings from Botswana that indicated potential safety concerns in pregnancy, with a small increased risk of neural tube defects.[3] Studies that investigated the safety and efficacy of DTG now support its use in all populations, including pregnant women and those of childbearing potential