HIV-1 drug resistance and genetic diversity in a cohort of people with HIV-1 in Nigeria

Abstract

Objective: This study was designed to provide information on the genetic diversity of HIV-1 and drug resistance mutations in Nigeria, as there is limited understanding of variants circulating in the country. Methods: We used an advanced next-generation sequencing platform, Primer ID, to: investigate the presence of high and low abundance drug resistance mutations; characterize preexisting Integrase Strand Transfer Inhibitor (INSTI) mutations in antiretroviral therapy (ART)-experienced but dolutegravir-naive individuals; detect recent HIV-1 infections and characterize subtype diversity from a cohort of people with HIV-1 (PWH). Results: HIV-1 subtype analysis revealed the predominance of CRF02_AG and subtype G in our study population. At detection sensitivity of 30% abundance, drug resistance mutations (DRMs) were identified in 3% of samples. At a sensitivity level of 10%, DRMs were identified in 27.3% of samples. We did not detect any major INSTI mutation associated with dolutegravir-resistance. Only one recent infection was detected in our study population. Conclusion: Our study suggests that dolutegravir-containing antiretroviral regimens will be effective in Nigeria. Our study also further emphasizes the high genetic diversity of HIV-1 in Nigeria and that CRF02_AG and subtype G are the dominant circulating forms of HIV-1 in Nigeria. These two circulating forms of the virus are largely driving the epidemic in the country.

HIV-1 drug resistance and genetic diversity in people with HIV-1 in Cape Verde

“…The pattern and frequency of the most common mutations, such as M184V/I (43%), TAMs (M41L, D67N, K70E/R, L210W, T215F/I/L/V/Yand K219Q/ E) (29%), K103N/S (36%), G190A/S (19%) and V106A/ I/M (12%) were similar to previous reports from Cape Verde and other low-income and middle-income countries [16][17][18][19][20][21][22][23][24][35][36][37] and consistent with the preferred first-line regimen of our patients…”

Analysis of mutational history of multidrug‐resistant genotypes with a mutagenetic tree model

“…5,6 The emergence of mutations in the HIV genome is highly correlated with drug resistance, because selective pressure presented by the drug therapy allows mutated viruses to escape the drug's action. 7,8 Especially, since evolutionary pressure allows mutated subpopulations to replace the original population, which was susceptible to the drug. 9 Which mutations strongly influence the resistance to multiple drugs and the order in which they tend to arise is still not completely known.…”

Anticipating HIV drug resistance with appropriate sequencing methods

“…Integrase strand transfer inhibitors (INSTIs) are important tools in antiretroviral therapies globally. Thankfully, the results reported by Oluniyi et al [1] do not yet preclude the use of INSTIs in Nigeria. We recently developed a tractable method to create HIV transcript models from high-quality long-read data [10,11].…”

“…Oluniyi et al [1] continue a pattern of excellent HIV sequencing work in Africa generally and Nigeria specifically. Local sequencing and data analysis with incidental international partnerships are representative of current biomedical research standards and are a departure from prior colonial science.…”

“…Generating one consensus sequence per patient at a given timepoint is a practical necessity for HIV molecular epidemiology but hinders HIV genotyping. Oluniyi et al [1] solved the problem of detecting absolute HIV cDNA amplicon abundance and therefore variants within their primer windows with previously developed UMI-based Primer ID [3]. Newer methods such as native or direct RNA sequencing from Oxford Nanopore Technologies (ONT) can sequence full-length HIV mRNAs, including both unspliced and spliced HIV mRNAs directly without the need for PCR or cDNA sequencing [8,9].…”