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The effect of interventions on the transmission and spread of HIV in South Africa: a phylodynamic analysis.

ABSTRACT: The epidemic in South Africa is characterized by high genetic diversity driven by multiple independent introductions. The bulk of these introductions occurred between 1985-2000 during which time HIV prevalence increased exponentially. Epidemic growth has stabilized in recent years with the implementation of several interventions. Here we identified distinct HIV clades from a large sequence dataset of southern African HIV sequences (n = 15,332). Each clade was characterized using phylodynamic and phylogeographic methods to infer their growth through time and space. The estimated date of origin for the 18 clades that were found, fell between 1979-1992 with strong growth during the 1990's. Phylogeographic reconstruction revealed wide dispersal of clades throughout the country with the city of Johannesburg as the focal point of viral dispersal. We found clear signs of decreasing growth rate in four of the clades since the advent of interventions, while other clades have continued to growth and expand. Our results demonstrate that interventions do not affect the HIV epidemic universally with major difference between different clades over time and space. Here we demonstrate the utility and flexibility of molecular epidemiological methods and demonstrate how they can potentially be a powerful tool in HIV epidemic monitoring in South Africa.

SUBMITTER: Wilkinson E

PROVIDER: S-EPMC6389914 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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The effect of interventions on the transmission and spread of HIV in South Africa: a phylodynamic analysis.

Wilkinson Eduan E Junqueira Dennis Maletich DM Lessells Richard R Engelbrecht Susan S van Zyl Gert G de Oliveira Tulio T Salemi Marco M

Scientific reports 20190225 1

The epidemic in South Africa is characterized by high genetic diversity driven by multiple independent introductions. The bulk of these introductions occurred between 1985-2000 during which time HIV prevalence increased exponentially. Epidemic growth has stabilized in recent years with the implementation of several interventions. Here we identified distinct HIV clades from a large sequence dataset of southern African HIV sequences (n = 15,332). Each clade was characterized using phylodynamic and ...[more]

PMID: 30804361

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Project description:BackgroundRecent clinical trials of male circumcision, oral pre-exposure prophylaxis (PrEP), and a vaginal microbicide gel have shown partial effectiveness at reducing HIV transmission, stimulating interest in implementing portfolios of biomedical prevention programs.ObjectiveTo evaluate the effectiveness and cost-effectiveness of combination biomedical HIV prevention and treatment scale-up in South Africa, given uncertainty in program effectiveness.DesignDynamic HIV transmission and disease progression model with Monte Carlo simulation and cost-effectiveness analysis.ParticipantsMen and women aged 15 to 49 years in South Africa.InterventionsHIV screening and counseling, antiretroviral therapy (ART), male circumcision, PrEP, microbicide, and select combinations.Main measuresHIV incidence, prevalence, discounted costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios.Key resultsProviding half of all uninfected persons with PrEP averts 28 % of future HIV infections for $9,000/QALY gained, but the affordability of such a program is questionable. Given limited resources, annual HIV screening and ART utilization by 75 % of eligible infected persons could avert one-third of new HIV infections, for approximately $1,000/QALY gained. Male circumcision is more cost-effective, but disproportionately benefits men. A comprehensive portfolio of expanded screening, ART, male circumcision, microbicides, and PrEP could avert 62 % of new HIV infections, reducing HIV prevalence from a projected 14 % to 10 % after 10 years. This strategy doubles treatment initiation and adds 31 million QALYs to the population. Despite uncertainty in program effectiveness, a comprehensive portfolio costs less than $10,000/QALY gained in 33 % of simulation iterations and less than $30,000/QALY gained in 90 % of iterations, assuming an annual microbicide cost of $100.ConclusionsA portfolio of modestly-effective biomedical HIV prevention programs, including male circumcision, vaginal microbicides, and oral PrEP, could substantially reduce HIV incidence and prevalence in South Africa and be likely cost-effective. Given limited resources, PrEP is the least cost-effective intervention of those considered.

Project description:Adolescents and young people account for 40% of all new HIV infections each year, with South Africa one of the hardest hit countries, and having the largest population of people living with HIV. Although adolescent HIV prevention has been delivered through diverse modalities in South Africa, and although family-based approaches for adolescent HIV prevention have great potential for highly affected settings such as South Africa, there is a scarcity of empirically tested family-based adolescent HIV preventive interventions in this setting. We therefore conducted focus groups and in-depth interviews with key informants including clinicians, researchers, and other individuals representing organizations providing HIV and related health services to adolescents and parents (N = 82). We explored family perspectives and interactions around topics such as communication about sex, HIV, and relationships. Participants described aspects of family interactions that presented both challenges and opportunities for family-based adolescent HIV prevention. Parent-child communication on sexual topics were taboo, with these conversations perceived by some adults as an invitation for children to engage in HIV risk behavior. Parents experienced social sanctions for discussing sex and adolescents who asked about sex were often viewed as disrespectful and needing discipline. However, participants also identified context-appropriate strategies for addressing family challenges around HIV prevention including family meetings, communal parenting, building efficacy around parent-adolescent communication around sexual topics, and the need to strengthen family bonding and positive parenting. Findings indicate the need for a family intervention and identify strategies for development of family-based interventions for adolescent HIV prevention. These findings will inform design of a family intervention to be tested in a randomized pilot trial (ClinicalTrials.gov #NCT02432352).

Project description:IntroductionIn generalized epidemic settings, there is insufficient understanding of how the unmet HIV prevention and treatment needs of key populations (KPs), such as female sex workers (FSWs) and men who have sex with men (MSM), contribute to HIV transmission. In such settings, it is typically assumed that HIV transmission is driven by the general population. We estimated the contribution of commercial sex, sex between men, and other heterosexual partnerships to HIV transmission in South Africa (SA).MethodsWe developed the "Key-Pop Model"; a dynamic transmission model of HIV among FSWs, their clients, MSM, and the broader population in SA. The model was parameterized and calibrated using demographic, behavioural and epidemiological data from national household surveys and KP surveys. We estimated the contribution of commercial sex, sex between men and sex among heterosexual partnerships of different sub-groups to HIV transmission over 2010 to 2019. We also estimated the efficiency (HIV infections averted per person-year of intervention) and prevented fraction (% IA) over 10-years from scaling-up ART (to 81% coverage) in different sub-populations from 2020.ResultsSex between FSWs and their paying clients, and between clients with their non-paying partners contributed 6.9% (95% credibility interval 4.5% to 9.3%) and 41.9% (35.1% to 53.2%) of new HIV infections in SA over 2010 to 2019 respectively. Sex between low-risk groups contributed 59.7% (47.6% to 68.5%), sex between men contributed 5.3% (2.3% to 14.1%) and sex between MSM and their female partners contributed 3.7% (1.6% to 9.8%). Going forward, the largest population-level impact on HIV transmission can be achieved from scaling up ART to clients of FSWs (% IA = 18.2% (14.0% to 24.4%) or low-risk individuals (% IA = 20.6% (14.7 to 27.5) over 2020 to 2030), with ART scale-up among KPs being most efficient.ConclusionsClients of FSWs play a fundamental role in HIV transmission in SA. Addressing the HIV prevention and treatment needs of KPs in generalized HIV epidemics is central to a comprehensive HIV response.

Project description:IntroductionMonitoring mother-infant pairs with HIV exposure is needed to assess the effectiveness of vertical transmission (VT) prevention programmes and progress towards VT elimination.MethodsWe used routinely collected data on infants with HIV exposure, born May 2018-April 2021 in the Western Cape, South Africa, with follow-up through mid-2022. We assessed the proportion of infants diagnosed with HIV at birth (≤7 days), 10 weeks (>1 to 14 weeks) and >14 weeks as proxies for intrauterine, intrapartum/early breastfeeding and late breastfeeding transmission, respectively. We used mixed-effects Poisson regression to assess factors associated with VT in mothers known with HIV by delivery.ResultsWe included 50,461 infants born to mothers known with HIV by delivery. HIV was diagnosed in 894 (1.8%) infants. Among mothers, 51% started antiretroviral treatment (ART) before and 27% during pregnancy; 17% restarted during pregnancy after ≥6 months interruption; and 6% had no recorded ART during pregnancy. Most pregnancy ART regimens included non-nucleoside reverse transcriptase inhibitors (83%). Of mothers with available results (90% with viral load [VL]; 70% with CD4), VL nearest delivery was <100 copies/ml in 78% and CD4 count ≥350 cells/μl in 62%. HIV-PCR results were available for 86%, 67% and 48% of eligible infants at birth, 10 weeks and >14 weeks. Among these infants, 0.9%, 0.4% and 1.5% were diagnosed positive at birth, 10 weeks and >14 weeks, respectively. Among infants diagnosed with HIV, 43%, 16% and 41% were diagnosed at these respective time periods. Among mothers with VL<100, 100-999, 1000-99,000 and ≥100,000 copies/ml nearest delivery, infant HIV diagnosis incidence was 0.4%, 2.3%, 6.6% and 18.4%, respectively. Increased VT was strongly associated with recent elevated maternal VL with a seven-fold increased rate with even modestly elevated VL (100-999 vs. <100 copies/ml). VT was also associated with unknown/low maternal CD4, maternal age <20 years, no antenatal ART, later maternal ART start/restart in pregnancy and ART gaps.ConclusionsDespite high maternal ART coverage and routine postnatal prophylaxis, ongoing VT remains a concern. Timing of infant HIV diagnoses suggests intrapartum and/or breastfeeding transmission in nearly 60%. Interventions to ensure retention on ART and sustained maternal viral suppression are needed to reduce VT.

Project description:BackgroundFine scale geospatial analysis of HIV infection patterns can be used to facilitate geographically targeted interventions. Our objective was to use the geospatial technology to map age and time standardized HIV incidence rates over a period of 10 years to identify communities at high risk of HIV in the greater Durban area.MethodsHIV incidence rates from 7557 South African women enrolled in five community-based HIV prevention trials (2002-2012) were mapped using participant household global positioning system (GPS) coordinates. Age and period standardized HIV incidence rates were calculated for 43 recruitment clusters across greater Durban. Bayesian conditional autoregressive areal spatial regression (CAR) was used to identify significant patterns and clustering of new HIV infections in recruitment communities.ResultsThe total person-time in the cohort was 9093.93 years and 613 seroconversions were observed. The overall crude HIV incidence rate across all communities was 6·74 per 100PY (95% CI: 6·22-7·30). 95% of the clusters had HIV incidence rates greater than 3 per 100PY. The CAR analysis identified six communities with significantly high HIV incidence. Estimated relative risks for these clusters ranged from 1.34 to 1.70. Consistent with these results, age standardized HIV incidence rates were also highest in these clusters and estimated to be 10 or more per 100 PY. Compared to women 35+ years old younger women were more likely to reside in the highest incidence areas (aOR: 1·51, 95% CI: 1·06-2·15; aOR: 1.59, 95% CI: 1·19-2·14 and aOR: 1·62, 95% CI: 1·2-2·18 for < 20, 20-24, 25-29 years old respectively). Partnership factors (2+ sex partners and being unmarried/not cohabiting) were also more common in the highest incidence clusters (aOR 1.48, 95% CI: 1.25-1.75 and aOR 1.54, 95% CI: 1.28-1.84 respectively).ConclusionFine geospatial analysis showed a continuous, unrelenting, hyper HIV epidemic in most of the greater Durban region with six communities characterised by particularly high levels of HIV incidence. The results motivate for comprehensive community-based HIV prevention approaches including expanded access to PrEP. In addition, a higher concentration of HIV related services is required in the highest risk communities to effectively reach the most vulnerable populations.

Dataset Information

The effect of interventions on the transmission and spread of HIV in South Africa: a phylodynamic analysis.

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The effect of interventions on the transmission and spread of HIV in South Africa: a phylodynamic analysis.

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