HIV Treatment as Prevention: Optimising the Impact of Expanded HIV Treatment Programmes
TL;DR: In re-evaluating the allocation of ART in light of the new data about ART preventing transmission, the goal should be to create policies that maximise epidemiological and clinical benefit while still being feasible, affordable, acceptable, and equitable.
Abstract: Until now, decisions about how to allocate ART have largely been based on maximising the therapeutic benefit of ART for patients. Since the results of the HPTN 052 study showed efficacy of antiretroviral therapy (ART) in preventing HIV transmission, there has been increased interest in the benefits of ART not only as treatment, but also in prevention. Resources for expanding ART in the short term may be limited, so the question is how to generate the most prevention benefit from realistic potential increases in the availability of ART. Although not a formal systematic review, here we review different ways in which access to ART could be expanded by prioritising access to particular groups based on clinical or behavioural factors. For each group we consider (i) the clinical and epidemiological benefits, (ii) the potential feasibility, acceptability, and equity, and (iii) the affordability and cost-effectiveness of prioritising ART access for that group. In re-evaluating the allocation of ART in light of the new data about ART preventing transmission, the goal should be to create policies that maximise epidemiological and clinical benefit while still being feasible, affordable, acceptable, and equitable.
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TL;DR: It is suggested that FSWs can achieve levels of ART uptake, retention, adherence, and treatment response comparable to that seen among women in the general population, but these data are from only a few research settings.
Abstract: Purpose
We aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.
124 citations
Cites background from "HIV Treatment as Prevention: Optimi..."
...To date, this is the first study to systematically review and quantify the ART cascade among FSWs globally, which builds on a limited review already undertaken by the authors [15]....
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...transmitting HIV [15,17], it is crucial to understand the extent to which FSWs currently access ART, and continue ART with good adherence....
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...Ensuring high levels of ART uptake, adherence and retention among FSWs, would provide not only individual benefits to HIV-infected FSWs, but could also help reduce HIV transmission at the population level [15,16]....
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TL;DR: Sensitising health workers through specialised training, refining referral systems from sex-worker friendly clinics into the national system, and providing opportunities for SW to collectively organise for improved treatment and rights might help alleviate the barriers to treatment initiation and attention currently faced by SW.
Abstract: Although disproportionately affected by HIV, sex workers (SWs) remain neglected by efforts to expand access to antiretroviral treatment (ART). In Zimbabwe, despite the existence of well-attended services targeted to female SWs, fewer than half of women diagnosed with HIV took up referrals for assessment and ART initiation; just 14% attended more than one appointment. We conducted a qualitative study to explore the reasons for non-attendance and the high rate of attrition. Three focus group discussions (FGD) were conducted in Harare with HIV-positive SWs referred from the ‘Sisters with a Voice’ programme to a public HIV clinic for ART eligibility screening and enrolment. Focus groups explored SWs’ experiences and perceptions of seeking care, with a focus on how managing HIV interacted with challenges specific to being a sex worker. FGD transcripts were analyzed by identifying emerging and recurring themes that were specifically related to interactions with health services and how these affected decision-making around HIV treatment uptake and retention in care. SWs emphasised supply-side barriers, such as being demeaned and humiliated by health workers, reflecting broader social stigma surrounding their work. Sex workers were particularly sensitive to being identified and belittled within the health care environment. Demand-side barriers also featured, including competing time commitments and costs of transport and some treatment, reflecting SWs’ marginalised socio-economic position. Improving treatment access for SWs is critical for their own health, programme equity, and public health benefit. Programmes working to reduce SW attrition from HIV care need to proactively address the quality and environment of public services. Sensitising health workers through specialised training, refining referral systems from sex-worker friendly clinics into the national system, and providing opportunities for SW to collectively organise for improved treatment and rights might help alleviate the barriers to treatment initiation and attention currently faced by SW.
100 citations
Cites background from "HIV Treatment as Prevention: Optimi..."
...At the same time, the “Universal Access” agenda has made equity a guiding principle for national programmes, leading to greater prioritisation of key populations, including sex workers [10,11]....
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TL;DR: Migration and globalization has contributed to the spread of non-B subtypes contributing to 20–60% of new infections in Europe, Asia and America.
Abstract: In 30 years, the HIV-1/AIDS pandemic has evolved into an increasingly complex disease composed of multiple epidemics, each influenced by a complex array of biological, behavioural and cultural factors [1–4]. The concentrated subtype B epidemics in Western world settings have been largely restricted to MSM and IDU populations [3]. The generalized heterosexual (HET) epidemics in Africa and Asia have expanded and diversified to include nine major HIV-1 subtypes (A–D, F–H, J and K) and mosaic circulating recombinant forms (e.g. CRF01_AE and CRF02_AG) [1,5,6]. Migration and globalization has contributed to the spread of non-B subtypes contributing to 20–60% of new infections in Europe, Asia and America [1,2,7].
83 citations
TL;DR: It is hoped that the principles described here will become a shared resource that facilitates constructive discussions about the policy implications that emerge from HIV epidemiology modelling results, and that promotes joint understanding about when modelling is useful as a tool in quantifying HIV epidemiological outcomes and improving prevention programming.
Abstract: Public health responses to HIV epidemics have long relied on epidemiological modelling analyses to help prospectively project and retrospectively estimate the impact, cost-effectiveness, affordability, and investment returns of interventions, and to help plan the design of evaluations. But translating model output into policy decisions and implementation on the ground is chal- lenged by the differences in background and expectations of modellers and decision-makers. As part of the PLoS Medicine Collection ''Investigating the Impact of Treat- ment on New HIV Infections''—which focuses on the contribution of modelling to current issues in HIV prevention—we present here principles of ''best practice'' for the construction, reporting, and interpretation of HIV epidemiological models for public health decision-making on all aspects of HIV. Aimed at both those who conduct modelling research and those who use modelling results, we hope that the principles described here will become a shared resource that facilitates constructive discussions about the policy implications that emerge from HIV epidemiology modelling results, and that promotes joint understanding between modellers and decision-makers about when modelling is useful as a tool in quantifying HIV epidemiological outcomes and improving prevention programming.
83 citations
Cites background from "HIV Treatment as Prevention: Optimi..."
...[19], or prioritised for treatment as prevention [20])....
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TL;DR: “treatment as prevention” for adult-to-adult transmission reduction includes expanded HIV testing, linkage to care, antiretroviral coverage, retention in care, adherence to therapy, and management of key co-morbidities such as depression and substance use.
Abstract: HIV research has identified approaches that can be combined to be more effective in transmission reduction than any 1 modality alone: delayed adolescent sexual debut, mutual monogamy or sexual partner reduction, correct and consistent condom use, pre-exposure prophylaxis with oral antiretroviral drugs or vaginal microbicides, voluntary medical male circumcision, antiretroviral therapy (ART) for prevention (including prevention of mother to child HIV transmission [PMTCT]), treatment of sexually transmitted infections, use of clean needles for all injections, blood screening prior to donation, a future HIV prime/boost vaccine, and the female condom. The extent to which evidence-based modalities can be combined to prevent substantial HIV transmission is largely unknown, but combination approaches that are truly implementable in field conditions are likely to be far more effective than single interventions alone. Analogous to PMTCT, “treatment as prevention” for adult-to-adult transmission reduction includes expanded HIV testing, linkage to care, antiretroviral coverage, retention in care, adherence to therapy, and management of key co-morbidities such as depression and substance use. With successful viral suppression, persons with HIV are far less infectious to others, as we see in the fields of sexually transmitted infection control and mycobacterial disease control (tuberculosis and leprosy). Combination approaches are complex, may involve high program costs, and require substantial global commitments. We present a rationale for such investments and cite an ongoing research agenda that seeks to determine how feasible and cost-effective a combination prevention approach would be in a variety of epidemic contexts, notably that in a sub-Saharan Africa.
78 citations
References
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TL;DR: It is demonstrated that higher concentrations of HIV-1 RNA in genital secretions are associated with a greater risk of heterosexual transmission of HIV, and that these concentrations provide a new biomarker for predicting the infectiousness of HIV–infected individuals.
Abstract: High plasma HIV-1 RNA concentrations are associated with an increased risk of HIV-1 transmission. Although plasma and genital HIV-1 RNA concentrations are correlated, no study has evaluated the relationship between genital HIV-1 RNA and the risk of heterosexual HIV-1 transmission. In a prospective study of 2521 African HIV-1 serodiscordant couples, we assessed genital HIV-1 RNA quantity and HIV-1 transmission risk. HIV-1 transmission linkage was established within the partnership by viral sequence analysis. We tested endocervical samples from 1805 women, including 46 who transmitted HIV-1 to their partner, and semen samples from 716 men, including 32 who transmitted HIV-1 to their partner. There was a correlation between genital and plasma HIV-1 RNA concentrations: For endocervical swabs, Spearman’s rank correlation coefficient r was 0.56, and for semen, r was 0.55. Each 1.0 log10 increase in genital HIV-1 RNA was associated with a 2.20-fold (for endocervical swabs: 95% confidence interval, 1.60 to 3.04) and a 1.79-fold (for semen: 95% confidence interval, 1.30 to 2.47) increased risk of HIV-1 transmission. Genital HIV-1 RNA independently predicted HIV-1 transmission risk after adjusting for plasma HIV-1 quantity (hazard ratio, 1.67 for endocervical swabs and 1.68 for semen). Seven female-to-male and four male-to-female HIV-1 transmissions (incidence <1% per year) occurred from persons with undetectable genital HIV-1 RNA, but in all 11 cases, plasma HIV-1 RNA was detected. Thus, higher genital HIV-1 RNA concentrations are associated with greater risk of heterosexual HIV-1 transmission, and this effect was independent of plasma HIV-1 concentrations. These data suggest that HIV-1 RNA in genital secretions could be used as a marker of HIV-1 sexual transmission risk.
287 citations
TL;DR: This is the first study to show that pregnancy increased the risk of female-to-male HIV-1 transmission, which may reflect biological changes of pregnancy that could increase HIV- 1 infectiousness.
Abstract: Background—Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1 infected women to male partners. Methods—In a prospective study of African HIV-1 serodiscordant couples, we evaluated the relationship between pregnancy and the risk of 1) HIV-1 acquisition among women and 2) HIV-1 transmission from women to men. Results—3321 HIV-1 serodiscordant couples were enrolled, 1085 (32.7%) with HIV-1 susceptible female partners and 2236 (67.3%) with susceptible male partners. HIV-1 incidence in women was 7.35 versus 3.01 per 100 person-years during pregnant and non-pregnant periods (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.33–4.09). This effect was attenuated and not statistically significant after adjusting for sexual behavior and other confounding factors (adjusted HR 1.71, 95% CI 0.93–3.12). HIV-1 incidence in male partners of infected women was 3.46 versus 1.58 per 100 person-years when their partners were pregnant versus not pregnant (HR
254 citations
"HIV Treatment as Prevention: Optimi..." refers background in this paper
...Further, it is known that couples in stable partnerships in which the HIV-infected individual has a high CD4 cell count are likely to conceive (16% per year among discordant couples [38]); therefore this strategy would incur many of the maternal and PMTCT-related health benefits described above [33]....
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...However, for serodiscordant couples, the femaleto-male transmission rate may be more than twice as high during pregnancy as during non-pregnant periods [38]....
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TL;DR: The evidence for effectiveness of HIV and sexually transmitted infection prevention interventions in female sex workers in resource poor settings is reviewed to systematically review the evidence.
Abstract: Summary objective To systematically review the evidence for effectiveness of HIV and sexually transmitted infection (STI) prevention interventions in female sex workers in resource poor settings method Published and unpublished studies were identified through electronic databases (Cochrane database, Medline, Embase, and Web of Science), hand searching and contacting experts Randomizedcontrolled-trials and quasi-experimental studies were included if they were conducted in female sex workersfromlowandmiddleincomesettings;iftheexposurewasdescribed;iftheoutcomewasexternally measurable, it was after the discovery of HIV, and if follow-up was longer than 6 months A priori criteria were used to extract data Meta-analysis was not performed due to the heterogeneity of studies results Twenty-eight interventions were included Despite methodological limitations, the evidence suggested that combining sexual risk reduction, condom promotion and improved access to STI treatment reduces HIV and STI acquisition in sex workers receiving the intervention Strong evidence that regular STI screening or periodic treatment of STIs confers additional protection against HIV was lacking It appears that structural interventions, policy change or empowerment of sex workers, reduce the prevalence of STIs and HIV conclusion Rigorous evaluation of HIV ⁄STI prevention interventions in sex workers is challenging There is some evidence for the efficacy of multi-component interventions, and ⁄or structural interventions The effect of these interventions on the wider population has rarely been evaluated
253 citations
"HIV Treatment as Prevention: Optimi..." refers background in this paper
...Previous modelling [81,82,87,88] and epidemiological analyses [89,90] suggest that prioritising interventions for FSWs and their clients in these settings can substantially reduce HIV transmission...
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TL;DR: Numbers on ART have increased rapidly in South Africa, but the programme has experienced deteriorating patient retention over time, particularly due to apparent LTFU, and new strategies are needed to improve monitoring of outcomes and maximize retention in care with increasing programme size.
Abstract: Little is known about the temporal impact of the rapid scale-up of large antiretroviral therapy (ART) services on programme outcomes. We describe patient outcomes [mortality, loss-to-follow-up (LTFU) and retention] over time in a network of South African ART cohorts.
250 citations
"HIV Treatment as Prevention: Optimi..." refers background in this paper
...Evidence from ART programmes in southern Africa indicates that high retention in care becomes increasingly challenging as treatment programmes expand [127]....
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University of Washington1, International Union Against Tuberculosis and Lung Disease2, University of London3, Kamuzu Central Hospital4, Médecins Sans Frontières5, Institute of Tropical Medicine Antwerp6, Imperial College London7, Joint United Nations Programme on HIV/AIDS8, The Global Fund to Fight AIDS, Tuberculosis and Malaria9
TL;DR: The authors propose offering all HIV-infected pregnant women lifelong ART which they see as a more feasible alternative to WHOs guidelines in addition to being more ethical.
242 citations
"HIV Treatment as Prevention: Optimi..." refers background in this paper
...A new option ‘‘B+’’ has been proposed, in which pregnant women would be eligible to immediately initiate lifelong ART regardless of HIV disease stage, TB disease status, or CD4 count [34]....
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