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      Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013–2014

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          Abstract

          Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort.

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          HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study.

          Francesca Conradie, Ferdinand Wit, Raph Hamers … (2011)
          There are few data on the epidemiology of primary HIV-1 drug resistance after the roll-out of antiretroviral treatment (ART) in sub-Saharan Africa. We aimed to assess the prevalence of primary resistance in six African countries after ART roll-out and if wider use of ART in sub-Saharan Africa is associated with rising prevalence of drug resistance. We did a cross-sectional study in antiretroviral-naive adults infected with HIV-1 who had not started first-line ART, recruited between 2007 and 2009 from 11 regions in Kenya, Nigeria, South Africa, Uganda, Zambia, and Zimbabwe. We did population-based sequencing of the pol gene on plasma specimens with greater than 1000 copies per mL of HIV RNA. We identified drug-resistance mutations with the WHO list for transmitted resistance. The prevalence of sequences containing at least one drug-resistance mutation was calculated accounting for the sampling weights of the sites. We assessed the risk factors of resistance with multilevel logistic regression with random coefficients. 2436 (94.1%) of 2590 participants had a pretreatment genotypic resistance result. 1486 participants (57.4%) were women, 1575 (60.8%) had WHO clinical stage 3 or 4 disease, and the median CD4 count was 133 cells per μL (IQR 62-204). Overall sample-weighted drug-resistance prevalence was 5.6% (139 of 2436; 95% CI 4.6-6.7), ranging from 1.1% (two of 176; 0.0-2.7) in Pretoria, South Africa, to 12.3% (22 of 179; 7.5-17.1) in Kampala, Uganda. The pooled prevalence for all three Ugandan sites was 11.6% (66 of 570; 8.9-14.2), compared with 3.5% (73 of 1866; 2.5-4.5) for all other sites. Drug class-specific resistance prevalence was 2.5% (54 of 2436; 1.8-3.2) for nucleoside reverse-transcriptase inhibitors (NRTIs), 3.3% (83 of 2436; 2.5-4.2) for non-NRTIs (NNRTIs), 1.3% (31 of 2436; 0.8-1.8) for protease inhibitors, and 1.2% (25 of 2436; 0.7-1.7) for dual-class resistance to NRTIs and NNRTIs. The most common drug-resistance mutations were K103N (43 [1.8%] of 2436), thymidine analogue mutations (33 [1.6%] of 2436), M184V (25 [1.2%] of 2436), and Y181C/I (19 [0.7%] of 2436). The odds ratio for drug resistance associated with each additional year since the start of the ART roll-out in a region was 1.38 (95% CI 1.13-1.68; p=0.001). The higher prevalence of primary drug resistance in Uganda than in other African countries is probably related to the earlier start of ART roll-out in Uganda. Resistance surveillance and prevention should be prioritised in settings where ART programmes are scaled up. Ministry of Foreign Affairs of the Netherlands. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Age-disparate and intergenerational sex in southern Africa: the dynamics of hypervulnerability.

            Suzanne Leclerc (2008)
            This paper reviews the current state of knowledge on age-disparate sexual relationships in the context of the southern African HIV/AIDS hyperepidemic. Disproportionately high HIV infection rates among young women aged 15-24 years have been attributed to their greater involvement in relationships with older-aged partners. Whereas early studies emphasized economic concerns in the context of poverty as driving girls to accept or seek the attentions of older employed men, close-grained studies reveal a complex interplay of meanings and motives that prompt both men and women across socioeconomic strata to engage in intergenerational sex. Studies have revealed that age-disparate relationships are meaningful and perceived as beneficial at a number of levels, including social, physical, psychological, as well as economic and symbolic. In the context of growing economic inequalities and cultural expectations for men to give and women to receive a compensation for sex, relationships with older men are a common and readily available way through which young women gain materially, affirm self-worth, achieve social goals, increase longer-term life chances, or otherwise add value and enjoyment to life. Awareness of HIV risks in these relationships remains low. HIV prevention policies and programmes need to start from an understanding of how those engaged in risky behaviour perceive their sexual relationships and conceptualize the choices they make and the strategies they use. A more comprehensive policy on women and girls with better integration of communities in assessing and addressing issues, and an expansion of campaigns and programmes on the role of men as protectors and supporters of women are recommended.
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              Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: a meta-analysis.

              Elise Arrivé, Marie-Louise Newell, Didier K. Ekouévi … (2007)
              Single-dose nevirapine (NVP) is the main option for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in countries with limited resources. However, the use of single-dose NVP results in HIV-1 viral resistance which could compromise the success of subsequent treatment of mother and child with antiretroviral combinations that include non-nucleosidic-reverse-transcriptase inhibitors. This systematic review and meta-analysis of summarized data aimed to estimate the proportion of mothers and children with NVP resistance mutations detected in plasma samples 4-8 weeks postpartum after single-dose NVP use for PMTCT. Systematic search of electronic databases (MEDLINE, PASCAL) and conference proceedings (1997 to February 2006). Inclusion of all studies, without design, place or language restrictions, meeting the following criteria: use of single-dose NVP; viral genotyping performed with standard sequence analyses, between 4 and 8 weeks postpartum, in plasma samples; available public report; report of mothers' median baseline plasma HIV-1 RNA levels. Data extraction by two independent reviewers using a standardized form created for this purpose. Logistic random effect models to obtain pooled estimates. Univariable and multivariable meta-regression to explore sources of heterogeneity. The pooled estimate of NVP resistance prevalence was 35.7% [95% confidence interval (CI) 23.0-50.6] in women in 10 study arms using single-dose NVP +/- other antepartum antiretrovirals and 4.5% (CI 2.1-9.4) in three study arms providing also postpartum antiretrovirals (adjusted odds ratio 0.08; CI 0.04-0.16). The corresponding estimates in children were 52.6% (CI 37.7-67.0) in seven study arms using single-dose NVP only and 16.5% (CI 8.9-28.3) in eight study arms combining single-dose NVP with other antiretrovirals. Single-dose NVP is widely used for PMTCT in resource-poor settings, but the burden of viral resistance is high in both women and children. It is substantially lower in studies providing additional postpartum antiretrovirals. The clinical implications of these findings should be further investigated.
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                Author and article information

                Journal
                Title: The Journal of Infectious Diseases
                Publisher: Oxford University Press (OUP)
                ISSN (Print): 0022-1899
                ISSN (Electronic): 1537-6613
                Publication date Created: December 15 2017
                Publication date Created: December 19 2017
                Publication date Created: October 10 2017
                Publication date Other: December 15 2017
                Publication date (Print): December 19 2017
                Publication date (Electronic): October 10 2017
                Volume: 216
                Issue: 12
                Pages: 1569-1578
                Affiliations
                [1 ]Department of Epidemiology, University of Washington, Seattle
                [2 ]Department of Global Health, University of Washington, Seattle
                [3 ]Seattle Children’s Research Institute, Washington
                [4 ]Department of Biostatistics, University of Washington, Seattle
                [5 ]Department of Medicine, University of Washington, Seattle
                [6 ]Department of Pediatrics, University of Washington, Seattle
                [7 ]Coptic Hospital, Nairobi
                [8 ]Department of Obstetrics and Gynaecology, University of Nairobi, Kenya
                [9 ]Department of Laboratory Medicine, University of Washington, Seattle
                Article
                DOI: 10.1093/infdis/jix544
                PMC ID: 5853791
                PubMed ID: 29040633
                SO-VID: f1afe804-4007-4436-8284-e8b51e21b85a
                Copyright © © 2017
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