Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment-experienced adults in northern Ghana

Nii-Trebi, Nicholas Israel; Brandful, James; Ibe, Shiro; Sugiura, Wataru; Barnor, Jacob Samson; Bampoh, Patrick Owiredu; Shoji, Yasuhiro; Matano, Tetsuro; Yoshimura, Kazuhisa; Ishikawa, Koichi; Ampofo, William

doi:10.1099/jmm.0.000621

Cited by 9 publications

(10 citation statements)

References 36 publications

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“…Regardless, our frequent observance of CRF02_AG along with unique recombinants, many of which contain CRF02_AG, is consistent with the ongoing generation and spread of HIV recombinant forms which now make up 23% of HIV infections globally [ 4 ]. Indeed, the high prevalence of URFs observed in this study is consistent with previous reports from Ghana [ 30 , 34 , 70 ]. High URF prevalence in the region is likely attributable to multiple factors, including high HIV subtype diversity in West Africa as well as socio-epidemiological factors.…”

Section: Discussionsupporting

confidence: 93%

“…While a study conducted on samples collected in 2003 from treatment-naïve Ghanaian PLWH reported no evidence of transmitted HIV drug resistance (TDR) [ 31 ], more recent studies have reported 9%, 11.5% and 33% TDR prevalence in children [ 32 ], pregnant women [ 33 ] and adults [ 27 ], respectively, though the number of individuals genotyped in these reports was relatively small. Acquired drug resistance is also a concern [ 28 , 32 ], with studies reporting 25–46% prevalence of the NNRTI resistance mutation K103N and a 39–54% prevalence of the NRTI resistance mutation M184V in persons failing ART [ 27 , 28 , 32 , 34 ]. Even fewer studies have investigated coreceptor usage, despite its relevance to the use of the HIV entry inhibitor maraviroc, which specifically inhibits viral entry via the CCR5 coreceptor (and is thus only effective in individuals who exclusively harbor CCR5-using HIV) [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Epidemiology of HIV-1 in Ghana: Subtype Distribution, Drug Resistance and Coreceptor Usage

Appah

Beelen

Kirkby

et al. 2022

Viruses

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The greatest HIV-1 genetic diversity is found in West/Central Africa due to the pandemic’s origins in this region, but this diversity remains understudied. We characterized HIV-1 subtype diversity (from both sub-genomic and full-genome viral sequences), drug resistance and coreceptor usage in 103 predominantly (90%) antiretroviral-naive individuals living with HIV-1 in Ghana. Full-genome HIV-1 subtyping confirmed the circulating recombinant form CRF02_AG as the dominant (53.9%) subtype in the region, with the complex recombinant 06_cpx (4%) present as well. Unique recombinants, most of which were mosaics containing CRF02_AG and/or 06_cpx, made up 37% of sequences, while “pure” subtypes were rare (<6%). Pretreatment resistance to at least one drug class was observed in 17% of the cohort, with NNRTI resistance being the most common (12%) and INSTI resistance being relatively rare (2%). CXCR4-using HIV-1 sequences were identified in 23% of participants. Overall, our findings advance our understanding of HIV-1 molecular epidemiology in Ghana. Extensive HIV-1 genetic diversity in the region appears to be fueling the ongoing creation of novel recombinants, the majority CRF02_AG-containing, in the region. The relatively high prevalence of pretreatment NNRTI resistance but low prevalence of INSTI resistance supports the use of INSTI-based first-line regimens in Ghana.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Molecular Epidemiology of HIV-1 in Ghana: Subtype Distribution, Drug Resistance and Coreceptor Usage

Appah

Beelen

Kirkby

et al. 2022

Viruses

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“…Therefore, more careful monitoring of HIV resistance is required in this region. However, the most recent data on DR in Guinea reported in the literature dates back to 2009, when the prevalence of primary DR was 8.9% 21 . In 2016, it was not possible to analyze a sufficient number of samples to identify the prevalence of DR in the Republic of Guinea 22 .…”

Section: Introductionmentioning

confidence: 99%

“…[18][19][20] A 2016 study confirmed the prevalence of CRF 02_AG in Guinea. 21 The Republic of Guinea is one of the countries affected by the Ebola epidemic. As such, there were significant difficulties in providing treatment to patients with HIV infection in the 2014-2015 period.…”

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confidence: 99%

Prevalence of drug resistant HIV‐1 forms in patients without any history of antiretroviral therapy in the Republic of Guinea

Щемелев

Boumbaly

Ostankova

et al. 2022

Journal of Medical Virology

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To study the structure of human immunodeficiency virus (HIV)‐1 drug resistance (DR) in patients with newly diagnosed infection. Residents of the Republic of Guinea (N = 2168) were tested for HIV using enzyme‐linked immunosorbent assay (ELISA). Individuals with a positive result were further examined for the presence of viral load in blood plasma. HIV was analyzed using Sanger sequencing. The obtained sequences were genotyped using REGA (version 3.0) and analyzed in MEGA 7. Analysis for the presence of DR mutations was performed using the Stanford University HIV DR Database. Serological markers of HIV were detected in 239 people, which represents 11.02% of the entire sample. HIV RNA was detected in 58 people. The following subtypes were seen: HIV CRF02_AG (41.9%); A1 (29.1%); A3 (12.9%); URF A1_G (12.9%); and G (3.2%). In 25% of patients, at least one significant mutation was encountered leading directly to HIV DR. The mutations encountered cause resistance to NRTI and NNRTI; one case of multiple resistance was identified. Major resistance to protease inhibitor was not seen. The detection of HIV‐1 mutations associated with DR, in individuals who have never received antiretroviral therapy, is a cause for concern. It suggests that: new infections are occurring with strains that already have resistance; and the expansion of resistance is not always directly associated with selective drug pressure. Among the likely reasons for the high prevalence of primary HIV DR in the Republic of Guinea, drug availability is probably the key. The consequence of this is the lack of adherence of patients to treatment, the formation and transmission of resistant variants of the virus in the population. These findings suggest the need to test patients for resistant virus variants before initiating treatment.

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“…Across all regions, the most frequently acquired DRMs were the 3TC/FTCassociated mutations at position M184 (range, 20% [Asia Pacific] to 70% [Africa]; Figure4B). for NRTI-associated DRMs and 3,191 individuals for NNRTI-associated DRMs (Supplemental Tables4 and 5in Additional file 1)[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]42]. Among reports with available data, 77% (n=702/917) and 80% (n=730/908) had acquired DRMs conferring resistance to the NRTI and NNRTI classes, respectively.…”

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confidence: 99%

Prevalence of Pretreatment and Acquired HIV-1 Mutations Associated with Resistance to Lamivudine or Rilpivirine: A Systematic Review

et al. 2018

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Background: Pretreatment and acquired drug resistance mutations (DRMs) can limit antiretroviral therapy effectiveness. Methods: We review prevalence of DRMs with resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), focusing on lamivudine and rilpivirine, from 127 articles with >100,000 individuals with HIV-1 infection. Results: Estimated global prevalence of pretreatment resistance to any NRTI was 4% and to any NNRTI was 6%.Most prevalent DRMs resistant to lamivudine or rilpivirine were at positions E138 (4%), V179 (1%) and M184 (1%). Estimated acquired DRM prevalence was 58% for any NRTIs and 67% for any NNRTIs, most frequently at positions M184 (58%) and Y181 (21%). Conclusions: This review suggests low risk of lamivudineor rilpivirine-resistant mutations in treatment-naive, HIV-1-infected individuals.

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Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment-experienced adults in northern Ghana

Cited by 9 publications

References 36 publications

Molecular Epidemiology of HIV-1 in Ghana: Subtype Distribution, Drug Resistance and Coreceptor Usage

Molecular Epidemiology of HIV-1 in Ghana: Subtype Distribution, Drug Resistance and Coreceptor Usage

Prevalence of drug resistant HIV‐1 forms in patients without any history of antiretroviral therapy in the Republic of Guinea

Prevalence of Pretreatment and Acquired HIV-1 Mutations Associated with Resistance to Lamivudine or Rilpivirine: A Systematic Review

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