Abstract
Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3′polypurine tract (3′-PPT). With anticipated shifts in Africa (where 25.6-million HIV-infected people resides) to INSTIs-based ART, it is critical to monitor patients in African countries for resistance-associated mutations (RAMs) affecting INSTIs efficacy. We analyzed HIV-1 integrase and 3′-PPT sequences in 345 clinical samples from INSTIs-naïve HIV-infected Cameroonians for polymorphisms and RAMs that affect INSTIs. Phylogeny showed high genetic diversity, with the predominance of HIV-1 CRF02_AG. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3′23.5% of samples). Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3′-PPT mutations. The low frequency of major INSTIs RAMs shows that INSTIs-based ART can be successfully used in Cameroon. Several samples had ≥1 INSTIs accessory RAMs known to reduce INSTIs efficacy; thus, INSTIs-based ART would require genetic surveillance. The 3′-PPT mutations could also affect INSTIs. For patients failing INSTIs-based ART with no INSTIs RAMs, monitoring 3′-PPT sequences could reveal treatment failure etiology.
Highlights
During HIV replication, the integrase enzyme catalyzes the ligation of viral reverse-transcribed DNA into the chromosome of the host cells
integrase strand transfer inhibitors (INSTIs) are recommended as part of initial or preferred antiretroviral therapy (ART) regimens for most HIV-infected people in western countries [7,10] and are recommended by the World Health Organization (WHO) as alternative 1st-line regimens for adults living with HIV/AIDS [11,12]
Global 2018 estimates show that DTG was used in only 4% of 1st-line ART regimens and in 6% of 2nd-line regimens, it is projected that by the year 2025, DTG, including single pills containing DTG and other antiretroviral drugs (ARVs), will be used by up to 57% of people living with HIV (PLWH) [16]
Summary
During HIV replication, the integrase enzyme catalyzes the ligation of viral reverse-transcribed DNA into the chromosome of the host cells. WHO is recommending DTG as alternative 1st-line regimen [11,12], its use is currently rare in resource-limited countries and it is estimated that only two countries in Sub-Saharan Africa (SSA), Kenya and Botswana, are currently providing DTG to HIV-infected persons as part of 1st-line ART regimens [13,14]. Global 2018 estimates show that DTG was used in only 4% of 1st-line ART regimens and in 6% of 2nd-line regimens, it is projected that by the year 2025, DTG, including single pills containing DTG and other antiretroviral drugs (ARVs), will be used by up to 57% of people living with HIV (PLWH) [16]
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