SUMMARY Female sex workers (FSWs) bear a disproportionately large burden of HIV infection worldwide. Despite decades of research and programme activity, the epidemiology of HIV and the role that structural determinants have in mitigating or potentiating HIV epidemics and access to care for FSWs is poorly understood. We reviewed available published data for HIV prevalence and incidence, condom use, and structural determinants among this group. Only 87 (43%) of 204 unique studies reviewed explicitly examined structural determinants of HIV. Most studies were from Asia, with few from areas with a heavy burden of HIV such as sub-Saharan Africa, Russia, and eastern Europe. To further explore the potential effect of structural determinants on the course of epidemics, we used a deterministic transmission model to simulate potential HIV infections averted through structural changes in regions with concentrated and generalised epidemics, and high HIV prevalence among FSWs. This modelling suggested that elimination of sexual violence alone could avert 17% of HIV infections in Kenya (95% uncertainty interval [UI] 1–31) and 20% in Canada (95% UI 3–39) through its immediate and sustained effect on non-condom use) among FSWs and their clients in the next decade. In Kenya, scaling up of access to antiretroviral therapy among FSWs and their clients to meet WHO eligibility of a CD4 cell count of less than 500 cells per μL could avert 34% (95% UI 25–42) of infections and even modest coverage of sex worker-led outreach could avert 20% (95% UI 8–36) of infections in the next decade. Decriminalisation of sex work would have the greatest effect on the course of HIV epidemics across all settings, averting 33–46% of HIV infections in the next decade. Multipronged structural and community-led interventions are crucial to increase access to prevention and treatment and to promote human rights for FSWs worldwide.

The idiopathic inf lammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, nonMendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) ‫؍‬ 2.29, P ‫؍‬ 5.7 ؋ 10 ؊4 ), with greatest significance for non-Ashkenazim Caucasians (MLod ‫؍‬ 3.39, P ‫؍‬ 3.92 ؋ 10 ؊5 ), and at chromosome 1p (MLod ‫؍‬ 2.65, P ‫؍‬ 2.4 ؋ 10 ؊4 ) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod ‫؍‬ 2.76, P ‫؍‬ 1.9 ؋ 10 ؊4 ), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod ‫؍‬ 1.69, P ‫؍‬ 2.6 ؋ 10 ؊3 ), particularly among Ashkenazim (MLod ‫؍‬ 1.51, P ‫؍‬ 7.8 ؋ 10 ؊3 ); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC.

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

PurposeWe aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.MethodsWe systematically searched PubMed, Embase and MEDLINE in March 2014 to identify studies reporting on ART uptake, attrition, adherence, and outcomes (viral suppression or CD4 count improvements) among HIV-infected FSWs globally. When possible, available estimates were pooled using random effects meta-analyses (with heterogeneity assessed using Cochran's Q test and I2 statistic).Results39 studies, reporting on 21 different FSW study populations in Asia, Africa, North America, South America, and Central America and the Caribbean, were included. Current ART use among HIV-infected FSWs was 38% (95% CI: 29%–48%, I2 = 96%, 15 studies), and estimates were similar between high-, and low- and middle-income countries. Ever ART use among HIV-infected FSWs was greater in high-income countries (80%; 95% CI: 48%–94%, I2 = 70%, 2 studies) compared to low- and middle-income countries (36%; 95% CI: 7%–81%, I2 = 99%, 3 studies). Loss to follow-up after ART initiation was 6% (95% CI: 3%–11%, I2 = 0%, 3 studies) and death after ART initiation was 6% (95% CI: 3%–11%, I2 = 0%, 3 studies). The fraction adherent to ≥95% of prescribed pills was 76% (95% CI: 68%–83%, I2 = 36%, 4 studies), and 57% (95% CI: 46%–68%, I2 = 82%, 4 studies) of FSWs on ART were virally suppressed. Median gains in CD4 count after 6 to 36 months on ART, ranged between 103 and 241 cells/mm3 (4 studies).ConclusionsDespite global increases in ART coverage, there is a concerning lack of published data on HIV treatment for FSWs. Available data suggest 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. More routine programme data on HIV treatment among FSWs across settings should be collected and disseminated.

Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges, since epidemics are principally driven by heterosexual transmission and a smaller fraction of cases is sampled. Here, we show that viral phylogenetic tools can be adapted and used to estimate epidemiological quantities of central importance to HIV-1 prevention in sub-Saharan Africa. We used a community-wide methods comparison exercise on simulated data, where participants were blinded to the true dynamics they were inferring. Two distinct simulations captured generalized HIV-1 epidemics, before and after a large community-level intervention that reduced infection levels. Five research groups participated. Structured coalescent modeling approaches were most successful: phylogenetic estimates of HIV-1 incidence, incidence reductions, and the proportion of transmissions from individuals in their first 3 months of infection correlated with the true values (Pearson correlation > 90%), with small bias. However, on some simulations, true values were markedly outside reported confidence or credibility intervals. The blinded comparison revealed current limits and strengths in using HIV phylogenetics in challenging settings, provided benchmarks for future methods’ development, and supports using the latest generation of phylogenetic tools to advance HIV surveillance and prevention.

Heterosexual anal intercourse confers a much greater risk of HIV transmission than vaginal intercourse, yet its contribution to heterosexual HIV epidemics has been under researched. In this article we review the current state of knowledge of heterosexual anal intercourse practice worldwide and identify the information required to assess its role in HIV transmission within heterosexual populations, including input measures required to inform mathematical models. We then discuss the evidence relating anal intercourse and HIV with sexual violence.

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Bill & Melinda Gates Foundation.