Impact of High-Risk Sex and Focused Interventions in Heterosexual HIV Epidemics: A Systematic Review of Mathematical Models

Background: The core-group theory of sexually transmitted infections suggests that targeting prevention to high-risk groups (HRG) could be very effective. We aimed to quantify the contribution of heterosexual HRGs and the potential impact of focused interventions to HIV transmission in the wider community. Methods: We systematically identified studies published between 1980 and 2011. Studies were included if they used dynamical models of heterosexual HIV transmission, incorporated behavioural heterogeneity in risk, and provided at least one of the following primary estimates in the wider community (a) the population attributable fraction (PAF) of HIV infections due to HRGs, or (b) the number per capita or fraction of HIV infections averted, or change in HIV prevalence/incidence due to focused interventions. Findings: Of 267 selected articles, 22 were included. Four studies measured the PAF, and 20 studies measured intervention impact across 265 scenarios. In low-prevalence epidemics (≤5% HIV prevalen

Health benefi ts, costs, and cost-eff ectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models

Background New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. Methods We used several independent mathematical models in four settings—South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)—to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost eff ective if the cost per DALY averted was less than the country’s 2012 per-head gross domestic product (GDP; South Africa:$8040; Zambia: $1425; India:$1489; Vietnam: $1407) and cost eff ective if the cost per DALY averted was less than three times the per-head GDP. Findings In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from$237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to$749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost eff ective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to$241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost eff ective. Interpretation Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost eff ective in lowincome and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

BACKGROUND: New WHO guidelines recommend ART initiation for HIV-positive persons with CD4 cell counts ≤500 cells/µL, a higher threshold than was previously recommended. Country decision makers must consider whether to further expand ART eligibility accordingly. METHODS: We used multiple independent mathematical models in four settings-South Africa, Zambia, India, and Vietnam-to evaluate the potential health impact, costs, and cost-effectiveness of different adult ART eligibility criteria under scenarios of current and expanded treatment coverage, with results projected over 20 years. Analyses considered extending eligibility to include individuals with CD4 ≤500 cells/µL or all HIV-positive adults, compared to the previous recommendation of initiation with CD4 ≤350 cells/µL. We assessed costs from a health system perspective, and calculated the incremental cost per DALY averted ($/DALY) to compare competing strategies. Strategies were considered 'very cost-effective' if the$/DALY was less than the country's per capita gross domestic product (GDP; South Africa: $8040, Zambia:$1425, India: $1489, Vietnam:$1407) and 'cost-effective' if $/DALY was less than three times per capita GDP. FINDINGS: In South Africa, the cost per DALY averted of extending ART eligibility to CD4 ≤500 cells/µL ranged from$237 to $1691/DALY compared to 2010 guidelines; in Zambia, expanded eligibility ranged from improving health outcomes while reducing costs (i.e. dominating current guidelines) to$749/DALY. Results were similar in scenarios with substantially expanded treatment access and for expanding eligibility to all HIV-positive adults. Expanding treatment coverage in the general population was therefore found to be cost-effective. In India, eligibility for all HIV-positive persons ranged from $131 to$241/DALY and in Vietnam eligibility for CD4 ≤500 cells/µL cost $290/DALY. In concentrated epidemics, expanded access among key populations was also cost-effective. INTERPRETATION: Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings, although these questions should be revisited as further information becomes available. Scaling-up ART should be considered among other high-priority health interventions competing for health budgets. FUNDING: The Bill and Melinda Gates Foundation and World Health Organization

Prevalence and correlates of anal intercourse among female sex workers in eSwatini.

IntroductionAs HIV is very effectively acquired during condomless receptive anal intercourse (AI) with serodiscordant and viremic partners, the practice could contribute to the high prevalence among female sex workers (FSW) in eSwatini (formerly known as Swaziland). We aim to estimate the proportion reporting AI (AI prevalence) among Swazi FSW and to identify the correlates of AI practice in order to better inform HIV prevention interventions among this population.MethodsUsing respondent-driven sampling (RDS), 325 Swazi FSW were recruited in 2011. We estimated the prevalence of AI and AI with inconsistent condom use in the past month with any partner type, and inconsistent condom use during AI and vaginal intercourse (VI) by partner type. Univariate and multivariable logistic regression models were used to identify behavioural and structural correlates associated with AI and AI with inconsistent condom use.ResultsRDS-adjusted prevalence of AI and AI with inconsistent condom use was high, at 44%[95% confidence interval (95%CI):35-53%]) and 34%[95%CI:26-42%], respectively and did not vary by partner type. HIV prevalence was high in this sample of FSW (70%), but knowledge that AI increases HIV acquisition risk low, with only 10% identifying AI as the riskiest sex act. Those who reported AI were more likely to be better educated (adjusted odds ratio(aOR) = 1.92[95%CI:1.03-3.57]), to have grown up in rural areas (aOR = 1.90[95%CI:1.09-3.32]), have fewer new clients in the past month (aOR = 0.33[95%CI:0.16-0.68]), and for last sex with clients to be condomless (aOR = 2.09[95%CI:1.07-4.08]). Although FSW reporting AI in past month were more likely to have been raped (aOR = 1.95[95%CI:1.05-3.65]) and harassed because of being a sex worker (aOR = 2.09[95%CI:1.16-3.74]), they were also less likely to have ever been blackmailed (aOR = 0.50[95%CI:0.25-0.98]) or been afraid to walk in public places (aOR = 0.46[95%CI:0.25-0.87]). Correlates of AI with inconsistent condom use were similar to those of AI.ConclusionsAI is commonly practised and condom use is inconsistent among Swazi FSW. Sex act data are needed to determine how frequently AI is practiced. Interventions to address barriers to condom use are needed, as are biomedical interventions that reduce acquisition risk during AI

HIV treatment as prevention: optimising the impact of expanded HIV treatment programmes.

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

Results from multivariate sensitivity analysis.

<p>Partial rank correlation coefficients (PRCC) between resistance parameters and intervention metrics: A) resistance prevalence due to PrEP (RP), B) cumulative fraction of infections in which resistance is transmitted (TRF), C) the fraction of infected individuals with elevated risk to fail ART and D) cumulative fraction of prevented infections (10-year CPF) and. Resistance parameters are sampled from their pooled ranges based on the responses to the virologists survey (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0158620#pone.0158620.t002" target="_blank">Table 2</a>). Linear increase of the ADR emergence rate with adherence to PrEP and PrEP efficacy per act proportional to adherence are assumed. Variation in the probabilities of ADR and TDR with respect of who is using PrEP when transmission occurs is considered. For instance (ADR transm: on->off) denotes the probability that ADR is transmitted from a PrEP user to a non-user.</p

Emergence and transmission of PrEP-associated resistance predicted by the virologists.

<p>A) rate of resistance emergence in infected PrEP users; B) relative infectiousness of the resistance carriers compared to infected with wild-type HIV; C) relative chance to transmit drug-resistant over wild-type HIV if resistance is acquired on PrEP (ADR); D) relative chance to transmit drug-resistant over wild-type HIV if resistance is acquired through transmission (TDR); E) PrEP protection against drug-resistant HIV and F) relative chance for viral suppression of the resistance carriers when ART is initiated. The bars (whiskers) represent the mean estimate (range) predicted by each respondent. Complete description of the survey results is provided in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0158620#pone.0158620.t002" target="_blank">Table 2</a>.</p

Dependence of the intervention outcomes on the resistance parameters.

<p>Dependence of the intervention outcomes on the resistance parameters.</p

Diagram of emergence and transmission of PrEP-associated drug-resistance.

<p>The diagram shows how resistance can occur in the presence of PrEP. The boxes represent different states in which individuals can be divided. These states include the use of PrEP by uninfected and infected individuals, as well as infected and HIV-infected individuals who do not use PrEP and HIV-infected individuals who carry PrEP-associated drug resistance. The processes contributing to PrEP-associated resistance include 1) transmission of resistance in which individuals become exposed to and infected with drug-resistant HIV (transmitted drug resistance, TDR), and 2) resistance that occur when individuals continue the use of PrEP after they become infected (acquired drug resistance, ADR). PrEP-associated resistance may drop below detectable level in individuals not exposed to PrEP for long period of time. They may lose the ability to transmit resistance but remain at elevated risk to fail ART when initiated.</p

Projections on the expected drug-resistance after 10 years of PrEP use based on the virologists’ opinion.

<p>A) resistance prevalence due to PrEP; B) cumulative fraction of infections in which resistance is transmitted (TRF) and C) the fraction of infected individuals with elevated risk to fail ART. The model is parameterized with the responses to the survey, assuming different levels of adherence to PrEP. The bars represent the mean metrics estimates based on 1,000 epidemics simulated. Intervention parameters are fixed on their baseline values from Table A, part 3 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0158620#pone.0158620.s001" target="_blank">S1 Text</a>.</p