Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone

Published on Aug 26, 2021in Genes4.096
· DOI :10.3390/GENES12091314
George A. Yendewa5
Estimated H-index: 5
,
Sulaiman Lakoh8
Estimated H-index: 8
+ 7 AuthorsNuno S. Osório15
Estimated H-index: 15
Sources
Abstract
Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2–9 years, 100% ART-experienced), 47 adolescents (age 10–18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), and V108I (18.8%, n = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), and K219N/E/Q/R (5.9%, n = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone.
References38
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#1George A. Yendewa (Case Western Reserve University)H-Index: 5
#2Sulaiman Lakoh (University of Sierra Leone)H-Index: 8
Last. Robert A. Salata (Case Western Reserve University)H-Index: 56
view all 17 authors...
Objective To assess the prevalence of serological markers of HBV and endemic acute and chronic infections (HAV, HCV, CMV, HTLV-1/2 and syphilis) in HIV-infected children, adolescents and pregnant women in Sierra Leone. Method We conducted a cross-sectional study at the national children's and women's hospitals in Freetown. Logistic regression was used to assess predictors of HBsAg positivity. Results 183 HIV-infected participants were enrolled, comprising children (n = 88), adolescents (n = 47) ...
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#1Kate El Bouzidi (UCL: University College London)H-Index: 5
#2Steven Kemp (UCL: University College London)H-Index: 12
Last. Ravindra K. Gupta (University of Cambridge)H-Index: 38
view all 18 authors...
OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-...
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#1Selase D. DeletsuH-Index: 2
#2Edward K Maina (College of Health Sciences, Bahrain)H-Index: 1
Last. Evelyn Y BonneyH-Index: 7
view all 6 authors...
This study sought to determine the dominant circulating human immunodeficiency virus type 1 (HIV-1) subtype and associated drug resistance mutations in Ghana.This cross-sectional study was conducted with archived samples collected from patients who received care at 2 hospitals in Ghana from 2014 to 2016. Blood samples were earlier processed into plasma and peripheral blood mononuclear cells and stored at -80 degrees C. Ribonucleic acid (RNA) was extracted from the archived plasma. Two HIV-1 gene...
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#1Sello Given Mikasi (UCT: University of Cape Town)H-Index: 4
#2J Gichana (UoN: University of Nairobi)H-Index: 3
Last. Graeme Brendon Jacobs (UCT: University of Cape Town)H-Index: 12
view all 12 authors...
The World Health Organization (WHO) has put forth recommendations for the use of Integrase (IN) strand transfers inhibitors (INSTIs) to be part of the first-line combination antiretroviral therapy ...
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In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services(dagger) (HHS) promptly issued interi...
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#1Philip L Tzou (Stanford University)H-Index: 8
#2Soo-Yon Rhee (Stanford University)H-Index: 33
Last. Robert W. Shafer (Stanford University)H-Index: 88
view all 15 authors...
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are expected to be widely adopted globally, requiring surveillance of resistance emergence and transmission. OBJECTIVES: We therefore sought to develop a standardized list of INSTI-resistance mutations suitable for the surveillance of transmitted INSTI resistance. METHODS: To characterize the suitability of the INSTI-resistance mutations for transmitted HIV-1 drug resistance (TDR) surveillance, we classified them according to their presen...
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#1Sulaiman Lakoh (University of Sierra Leone)H-Index: 8
#2Darlinda F. Jiba (University of Sierra Leone)H-Index: 6
Last. George A. Yendewa (Case Western Reserve University)H-Index: 5
view all 12 authors...
Background HIV infection is a growing public health problem in Sierra Leone and the wider West Africa region. The countrywide HIV prevalence was estimated at 1.7% (67,000 people), with less than 30% receiving life-saving ART in 2016. Thus, HIV-infected patients tend to present to health facilities late, with high mortality risk.
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#2Charles Kouanfack (IRD: Institut de recherche pour le développement)H-Index: 1
#3Mireille Mpoudi-Etame (IRD: Institut de recherche pour le développement)H-Index: 3
Last. Eric Delaporte (IRD: Institut de recherche pour le développement)H-Index: 78
view all 9 authors...
BACKGROUND: An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz-based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings. METHODS: We conducted an open-label, multicenter, randomized, phase 3 noninferiority tri...
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Abstract Background Two drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeficiency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafen...
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#1Rebecca ZashH-Index: 14
#2Lewis B. HolmesH-Index: 70
Last. Roger L. ShapiroH-Index: 46
view all 15 authors...
Abstract Background A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of ...
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