Antiretroviral Therapy to Prevent HIV Acquisition in Serodiscordant Couples in a Hyperendemic Community in Rural South Africa.
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ABSTRACT: Antiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in "real-life" population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other.Data arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships.We observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3-5.6), 1.4/100 PY (.4-3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5-8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI, .07-.80).ART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this "real-life" effect was substantially lower than the effect observed in the HPTN-052 trial. To eliminate HIV transmission in serodiscordant couples, additional prevention interventions are probably needed.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20160520 4
<h4>Background</h4>Antiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in "real-life" population-based settings ...[more]
Project description:ObjectivesWe investigate the effect of immediate antiretroviral therapy (ART) eligibility on HIV incidence among HIV-uninfected household members.DesignRegression discontinuity study arising from a population-based cohort.MethodsHousehold members of patients seeking care at the Hlabisa HIV Treatment and Care Programme in rural KwaZulu-Natal South Africa between January 2007 and August 2011 with CD4 cell counts up to 350 cells/μl were eligible for inclusion if they had at least two HIV tests and were HIV-uninfected at the time the index patient linked to care (N = 4115). Regression discontinuity was used to assess the intention-to-treat effect of immediate versus delayed ART eligibility on HIV incidence among household members. Exploiting the CD4 cell count-based threshold rule for ART initiation (CD4 < 200 cells/μl until August 2011), we used Cox proportional hazards models to compare outcomes for household members of patients who presented for care with CD4 cell counts just above versus just below the ART initiation threshold.ResultsCharacteristics of household members of index patients initiating HIV care were balanced between those with an index patient immediately eligible for ART (N = 2489) versus delayed for ART (N = 1626). There were 337 incident HIV infections among household members, corresponding to an HIV incidence of 2.4 infections per 100 person-years (95% confidence interval 2.5-3.1). Immediate eligibility for treatment reduced HIV incidence in households by 47% in our optimal estimate (hazard ratio = 0.53, 95% confidence interval 0.30-0.96), and by 32-60% in alternate specifications of the model.ConclusionImmediate eligibility of ART led to substantial reductions in household-level HIV incidence.
Project description:Antiretroviral treatment (ART) and pre-exposure prophylaxis (PrEP) for HIV-serodiscordant couples, effectively reduce mortality, transmission events and influence quality of life at the expense of increased costs. We aimed to evaluate health economics of antiretroviral-based strategies for HIV-serodiscordant couples in the China context. A deterministic model of HIV evolution and transmission within a cohort of serodiscordant couples was parameterized using the real-world database of Zhoukou city and published literature. We evaluated the mid-ART (a historical strategy, initiating ART with CD4 < 500 cells/mm3), early-ART (the current strategy, offering ART regardless of CD4 cell counts) and a hypothetical strategy (early-ART combined short-term daily PrEP) versus the late-ART (the baseline strategy, initiating ART with CD4 < 350 cells/mm3) offered by 2008 national guidelines. We estimated the incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICUR) from a societal perspective, derived by clinical benefits and HIV-caused life quality respectively, and portrayed their changes over a 0-30 year's timeframe. The model projections indicated that the antiretroviral-based interventions were more likely to obtain clinical benefits but difficult to improve quality of life, and cumulative ICER and ICUR were generally decreasing without achieving cost-saving. Scale-up access to ART for the HIV-positive among serodiscordant couples was easily fallen within the range of paying for incremental life-years and quality adjusted life years by the societal willingness. The hypothetical strategy had the potential to prevent most seroconversion events within marriages but required enormous upfront costs, thus it took a long time to reach established thresholds. The current strategy of early-ART is the most cost-effective. Clarifying the obstacles of high cost of PrEP and improving life quality for HIV-serodiscordant couples have emerged as an urgent requisition.
Project description:BackgroundAntiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.Methods and findingsWe constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is <40% of the annual cost of ART and PrEP is >70% effective.ConclusionsStrategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors' Summary.
Project description:To quantify the contribution of specific sexual partner age groups to the risk of HIV acquisition in men and women in a hyperendemic region of South Africa.We conducted a population-based cohort study among women (15-49 years of age) and men (15-55 years of age) between 2004 and 2015 in KwaZulu-Natal, South Africa.Generalized additive models were used to estimate smoothed HIV incidence rates across partnership age pairings in men and women. Cox proportional hazards regression was used to estimate the relative risk of HIV acquisition by partner age group.A total of 882 HIV seroconversions were observed in 15?935 person-years for women, incidence rate?=?5.5 per 100 person-years [95% confidence interval (CI), 5.2-5.9] and 270 HIV seroconversions were observed in 9372 person-years for men, incidence rate?=?2.9 per 100 person-years (95% CI, 2.6-3.2). HIV incidence was highest among 15-24-year-old women reporting partnerships with 30-34-year-old men, incidence rate?=?9.7 per 100 person-years (95% CI, 7.2-13.1). Risk of HIV acquisition in women was associated with male partners aged 25-29 years (adjusted hazard ratio; aHR?=?1.44, 95% CI, 1.02-2.04) and 30-34 years (aHR?=?1.50, 95% CI, 1.08-2.09) relative to male partners aged 35 and above. Risk of HIV acquisition in men was associated with 25-29-year-old (aHR?=?1.72, 95% CI, 1.02-2.90) and 30-34-year-old women (aHR?=?2.12, 95% CI, 1.03-4.39) compared to partnerships with women aged 15-19 years.Age of sexual partner is a major risk factor for HIV acquisition in both men and women, independent of one's own age. Partner age pairings play a critical role in driving the cycle of HIV transmission.
Project description:Estimation of causal effects from observational data is a primary goal of epidemiology. The use of multiple methods with different assumptions relating to exchangeability improves causal inference by demonstrating robustness across assumptions. We estimate the effect of antiretroviral therapy (ART) on mortality in rural KwaZulu-Natal, South Africa from 2007-2011 using two methods with substantially different assumptions: the regression discontinuity design (RDD), and inverse probability weighting of marginal structural models (IPW). The RDD analysis took advantage of a CD4 count-based threshold for ART initiation (200 cells/?l). The two methods yielded consistent but non-identical results for the effect of immediate initiation of ART (RDD intention-to-treat hazards ratio (HR) 0.66, 95% CI 0.35 to 1.26; RDD HR 0.56, 95% CI 0.41 to 0.77; IPW HR 0.49, 95% CI 0.42 to 0.58). Although RDD and IPW estimates had distinct identifying assumptions, strengths, and limitations in terms of internal and external validity, results in this application were similar. The differences in modeling approaches and external validity of each method may explain the minor differences in effect estimates, but the consistency of the results lends support for causal inference of the effect of ART and mortality from these data.
Project description:ObjectiveTo quantify the space-time dimensions of human mobility in relationship to the risk of HIV acquisition.MethodsWe used data from the population cohort located in a high HIV prevalence, rural population in KwaZulu-Natal, South Africa (2000-2014). We geolocated 8006 migration events (representing 1 028 782 km traveled) for 17 743 individuals (≥15 years of age) who were HIV negative at baseline and followed up these individuals for HIV acquisition (70 395 person-years). Based on the complete geolocated residential history of every individual in this cohort, we constructed two detailed time-varying migration indices. We then used interval-censored Cox proportional hazards models to quantify the relationship between the migration indices and the risk of HIV acquisition.ResultsIn total, 17.4% of participants migrated at least once outside the rural study community during the period of observation (median migration distance = 107.1 km, interquartile range 18.9-387.5). The two migration indices were highly predictive of hazard of HIV acquisition (P < 0.01) in both men and women. Holding other factors equal, the risk of acquiring HIV infection increased by 50% for migration distances of 40 km (men) and 109 km (women). HIV acquisition risk also increased by 50% when participants spent 44% (men) and 90% (women) of their respective time outside the rural study community.ConclusionThis in-depth analysis of a population cohort in a rural sub-Saharan African population has revealed a clear nonlinear relationship between distance migrated and HIV acquisition. Our findings show that even relatively short-distance migration events confer substantial additional risk of acquisition.
Project description:BackgroundStudies of HIV-serodiscordant couples in stable sexual relationships have provided convincing evidence that antiretroviral therapy can prevent the transmission of HIV. We aimed to quantify the preventive effect of a public-sector HIV treatment and care programme based in a community with poor knowledge and disclosure of HIV status, frequent migration, late marriage, and multiple partnerships. Specifically, we assessed whether an individual's hazard of HIV acquisition was associated with antiretroviral therapy coverage among household members of the opposite sex.MethodsIn this prospective cohort study, we linked patients' records from a public-sector HIV treatment programme in rural KwaZulu-Natal, South Africa, with population-based HIV surveillance data collected between 2004 and 2012. We used information about coresidence to construct estimates of HIV prevalence and antiretroviral therapy coverage for each household. We then regressed the time to HIV seroconversion for 14,505 individuals, who were HIV-uninfected at baseline and individually followed up over time regarding their HIV status, on opposite-sex household antiretroviral therapy coverage, controlling for household HIV prevalence and a range of other potential confounders.Findings2037 individual HIV seroconversions were recorded during 54,845 person-years of follow-up. For each increase of ten percentage points in opposite-sex household antiretroviral therapy coverage, the HIV acquisition hazard was reduced by 6% (95% CI 2–9), after controlling for other factors. This effect size translates into large reductions in HIV acquisition hazards when household antiretroviral therapy coverage is substantially increased. For example, an increase of 50 percentage points in household antiretroviral therapy coverage (eg, from 20% to 70%) reduced the hazard of HIV acquisition by 26% (95% CI 9–39).InterpretationOur findings provide further evidence that antiretroviral therapy significantly reduces the risk of onward transmission of HIV in a real-world setting in sub-Saharan Africa. Awareness that antiretroviral therapy can prevent transmission to coresident sexual partners could be a powerful motivator for HIV testing and antiretroviral treatment uptake, retention, and adherence.FundingWellcome Trust and National Institute of Child Health and Human Development (US National Institutes of Health).
Project description:INTRODUCTION:Serodiscordant couples are a priority population for delivery of new HIV prevention interventions in Africa. An integrated strategy of delivering time-limited, oral pre-exposure prophylaxis (PrEP) to uninfected partners in serodiscordant couples as a bridge to long-term antiretroviral treatment (ART) for infected partners has been implemented in East Africa, nearly eliminating new infections. We conducted a qualitative evaluation of the integrated strategy in Uganda, to better understand its success. METHODS:Data collection consisted of 274 in-depth interviews with 93 participating couples, and 55 observations of clinical encounters between couples and healthcare providers. An inductive content analytic approach aimed at understanding and interpreting couples' experiences of the integrated strategy was used to examine the data. Analysis sought to characterize: (1) key aspects of services provided; (2) what the services meant to recipients; and (3) how couples managed the integrated strategy. Themes were identified in each domain, and represented as descriptive categories. Categories were grouped inductively into more general propositions based on shared content. Propositions were linked and interpreted to explain "why the integrated strategy worked." RESULTS:Couples found "couples-focused" services provided through the integrated strategy strengthened partnered relationships threatened by the discovery of serodiscordance. They saw in services hope for "getting help" to stay together, turned joint visits to clinic into opportunities for mutual support, and experienced counselling as bringing them closer together. Couples adopted a "couples orientation" to the integrated strategy, considering the health of partners as they made decisions about initiating ART or accepting PrEP, and devising joint approaches to adherence. A couples orientation to services, grounded in strengthened partnerships, may have translated to greater success in using antiretrovirals to prevent HIV transmission. CONCLUSIONS:Various strategies for delivering antiretrovirals for HIV prevention are being evaluated. Understanding how and why these strategies work will improve evaluation processes and strengthen implementation platforms. We highlight the role of service organization in shaping couples' experiences of and responses to ART and PrEP in the context of the integrated strategy. Organizing services to promote positive care experiences will strengthen delivery and contribute to positive outcomes as antiretrovirals for prevention are rolled out.
Project description:Effectiveness of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention will require high adherence. Using qualitative data, this paper identifies potential lay social resources for support of PrEP adherence by HIV serodiscordant couples in Uganda, laying the groundwork for incorporation of these resources into adherence support initiatives as part of implementation. The qualitative analysis characterizes support for PrEP adherence provided by HIV-infected spouses, children, extended family members, and the larger community. Results suggest social resources for support of PrEP adherence in Africa are plentiful outside formal health care settings and health systems and that couples will readily use them. The same shortage of health professionals that impeded scale-up of antiretroviral treatment for HIV/AIDS in Africa promises to challenge delivery of PrEP. Building on the treatment scale-up experience, implementers can address this challenge by examining the value of lay social resources for adherence support in developing strategies for delivery of PrEP.
Project description:INTRODUCTION:High levels of HIV seroconcordance at the population level reduce the potential for effective HIV transmission. However, the level of HIV seroconcordance is largely unknown among heterosexual couples in sub-Saharan Africa. We aimed to quantify the population level HIV seroconcordance in stable heterosexual couples in rural South Africa. METHODS:We followed adults (≥15 years old) using a population-based, longitudinal and open surveillance system in KwaZulu-Natal, South Africa, from 2003 to 2016. Sexual partnerships and HIV status were confirmed via household surveys and annual HIV surveillance. We calculated the proportions of HIV seroconcordance and serodiscordance in stable sexual partnerships and compared them to the expected proportions under the assumption of random mixing using individual-based microsimulation models. Among unpartnered individuals, we estimated the incidence rates and hazard of sexual partnership formation with HIV-positive or HIV-negative partners by participants' own time-varying HIV status. Competing risks survival regressions were fitted adjusting for sociodemographic and clinical factors. We also calculated Newman's assortativity coefficients. RESULTS:A total of 18,341 HIV-negative and 11,361 HIV-positive individuals contributed 154,469 person-years (PY) of follow-up. Overall, 28% of the participants were in stable sexual partnerships. Of the 677 newly formed stable sexual partnerships, 7.7% (95% CI: 5.8 to 10.0) were HIV-positive seroconcordant (i.e. both individuals in the partnership were HIV-positive), which was three times higher than the expected proportion (2.3%) in microsimulation models based on random mixing. The incidence rates of sexual partnership formation were 0.54/1000PY with HIV-positive, 1.12/1000PY with HIV-negative and 2.65/1000PY with unknown serostatus partners. HIV-positive individuals had 2.39 (95% CI: 1.43 to 3.99) times higher hazard of forming a sexual partnership with an HIV-positive partner than did HIV-negative individuals after adjusting for age, opposite-sex HIV prevalence (by 5-years age groups), HIV prevalence in the surrounding community, ART coverage and other sociodemographic factors. Similarly, forming a sexual partnership with an HIV-negative partner was 1.47 (95% CI: 1.01 to 2.14) times higher in HIV-negative individuals in the adjusted model. Newman's coefficient also showed that assortativity by participant and partner HIV status was moderate (r = 0.35). CONCLUSIONS:A high degree of population level HIV seroconcordance (both positive and negative) was observed at the time of forming new sexual partnerships. Understanding factors driving these patterns may help the development of strategies to bring the HIV epidemic under control.
