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We conducted a prospective cohort study among HIV-negative MSM aged 18 years or older between 2007 and 2012 in Beijing, China to measure the rates of incident HIV and identify risk factors for infection. Among 5,800 participants evaluated at enrollment, we identified 486 prevalent cases of HIV (8.4%). Among the 3,625 enrollees who were HIV-negative at enrollment and completed at least one follow-up interview, we identified 440 incident cases of HIV in the follow up period: this constituted an HIV incidence rate of 7.1 per 100 person-years (95% CI: 6.4-7.7). Early treatment of syphilis may have significantly reduced risk of HIV infection (RR: 1.45, 95% CI: 1.11-1.93), while MSM presenting perfect compliance in the cohort did not show reduction in HIV infection. Our study suggested that HIV incidence has been remained high in this sample of Chinese MSM during the intensive preventive intervention, suggesting that we need to find new strategies to prevent HIV infection in this population.

Men who have sex with men (MSM) in India have an HIV seroprevalence 22 times greater than the country’s general population and face unique challenges that may hinder the effectiveness of current HIV prevention efforts. To obtain an understanding of the logistical and sociocultural barriers MSM experience while accessing HIV prevention services, focus groups and key informant interviews were conducted with 55 MSM in Chennai, India. Qualitative data were analyzed using descriptive qualitative content analysis. Sixty-five percent of participants identified as kothi (receptive partners), 9% as panthi (insertive partners), 22% as double decker (receptive and insertive), and 4% did not disclose. Themes included: (a) fatigue with current HIV risk reduction messages; (b) increased need for non-judgmental and confidential services; and (c) inclusion of content that acknowledges individual and structural-level determinants of risk such as low self-esteem, depression, and social discrimination. MSM interventions may benefit from approaches that address multilevel psychosocial factors, including skills building and strategies to foster self-acceptance and increased social support.

In this work, we estimate the proportions of transmissions occurring in main vs. casual partnerships, and by the sexual role, infection stage, and testing and treatment history of the infected partner, for men who have sex with men (MSM) in the US and Peru. We use dynamic, stochastic models based in exponential random graph models (ERGMs), obtaining inputs from multiple large-scale MSM surveys. Parallel main partnership and casual sexual networks are simulated. Each man is characterized by age, race, circumcision status, sexual role behavior, and propensity for unprotected anal intercourse (UAI); his history is modeled from entry into the adult population, with potential transitions including HIV infection, detection, treatment, AIDS diagnosis, and death. We implemented two model variants differing in assumptions about acute infectiousness, and assessed sensitivity to other key inputs. Our two models suggested that only 4–5% (Model 1) or 22–29% (Model 2) of HIV transmission results from contacts with acute-stage partners; the plurality (80–81% and 49%, respectively) stem from chronic-stage partners and the remainder (14–16% and 27–35%, respectively) from AIDS-stage partners. Similar proportions of infections stem from partners whose infection is undiagnosed (24–31%), diagnosed but untreated (36–46%), and currently being treated (30–36%). Roughly one-third of infections (32–39%) occur within main partnerships. Results by country were qualitatively similar, despite key behavioral differences; one exception was that transmission from the receptive to insertive partner appears more important in Peru (34%) than the US (21%). The broad balance in transmission contexts suggests that education about risk, careful assessment, pre-exposure prophylaxis, more frequent testing, earlier treatment, and risk-reduction, disclosure, and adherence counseling may all contribute substantially to reducing the HIV incidence among MSM in the US and Peru.

Background: Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India. Methods We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm\(^3\), and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH). Results: Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence. Conclusions: Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care.

Background: In 2010, the iPrEx trial demonstrated that oral antiretroviral pre-exposure prophylaxis (PrEP) reduced the risk of HIV acquisition among high-risk men who have sex with men (MSM). The impact of iPrEx on PrEP knowledge and actual use among at-risk MSM is unknown. Online surveys were conducted to assess PrEP awareness, interest and experience among at-risk MSM before and after iPrEx, and to determine demographic and behavioral factors associated with these measures. Methods and Findings: Cross-sectional, national, internet-based surveys were administered to U.S. based members of the most popular American MSM social networking site 2 months before (n = 398) and 1 month after (n = 4 558) publication of iPrEx results. Comparisons were made between these samples with regards to PrEP knowledge, interest, and experience. Data were collected on demographics, sexual risk, and experience with post-exposure prophylaxis (PEP). Regression analyses were performed to identify factors associated with PrEP awareness, interest, and experience post-iPrEx. Most participants were white, educated, and indicated high-risk sexual behaviors. Awareness of PrEP was limited pre- and post-iPrEx (13% vs. 19%), whereas interest levels after being provided with a description of PrEP remained high (76% vs. 79%). PrEP use remained uncommon (0.7% vs. 0.9%). PrEP use was associated with PEP awareness (OR 7.46; CI 1.52–36.6) and PEP experience (OR 34.2; CI 13.3–88.4). PrEP interest was associated with older age (OR 1.01; CI 1.00–1.02), unprotected anal intercourse with ≥1 male partner in the prior 3 months (OR 1.40; CI 1.10–1.77), and perceiving oneself at increased risk for HIV acquisition (OR 1.20; CI 1.13–1.27). Conclusions: Among MSM engaged in online networking, awareness of PrEP was limited 1 month after the iPrEx data were released. Utilization was low, although some MSM who reported high-risk behaviors were interested in using PrEP. Studies are needed to understand barriers to PrEP utilization by at-risk MSM.

Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies. Here, we report on a high-throughput whole HIV-1 genome deep sequencing platform that combines 454 pyrosequencing with novel assembly and variant detection algorithms. In one subject we combined these genetic data with detailed immunological analyses to comprehensively evaluate viral evolution and immune escape during the acute phase of HIV-1 infection. The majority of early, low frequency mutations represented viral adaptation to host CD8+ T cell responses, evidence of strong immune selection pressure occurring during the early decline from peak viremia. CD8+ T cell responses capable of recognizing these low frequency escape variants coincided with the selection and evolution of more effective secondary HLA-anchor escape mutations. Frequent, and in some cases rapid, reversion of transmitted mutations was also observed across the viral genome. When located within restricted CD8 epitopes these low frequency reverting mutations were sufficient to prime de novo responses to these epitopes, again illustrating the capacity of the immune response to recognize and respond to low frequency variants. More importantly, rapid viral escape from the most immunodominant CD8+ T cell responses coincided with plateauing of the initial viral load decline in this subject, suggestive of a potential link between maintenance of effective, dominant CD8 responses and the degree of early viremia reduction. We conclude that the early control of HIV-1 replication by immunodominant CD8+ T cell responses may be substantially influenced by rapid, low frequency viral adaptations not detected by conventional sequencing approaches, which warrants further investigation. These data support the critical need for vaccine-induced CD8+ T cell responses to target more highly constrained regions of the virus in order to ensure the maintenance of immunodominant CD8 responses and the sustained decline of early viremia.

BACKGROUND: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. METHODS: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. RESULTS: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01). CONCLUSIONS: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy.

Non-occupational post-exposure prophylaxis (nPEP) use is an HIV prevention strategy that has been recommended by the CDC to prevent HIV infection after a high risk sexual exposure since 1997. In a behavioral intervention trial of 4,295 MSM we assessed perceptions and use of nPEP over 4years in six cities across the United States. Overall, 1.9% of MSM reported use of nPEP prior to enrollment, and 6.3% at least once during the trial. Awareness of nPEP was reported by 47.5%, with higher awareness in two sites with funded nPEP programs. Three seroconversions occurred in the 384 visits where nPEP courses were reported, with no effect of nPEP on risk of HIV acquisition in this cohort (hazard ratio=0.91, 95% confidence interval [0.29, 2.86]). NPEP users were a riskier group: increased odds of nPEP use were observed in association with multiple partners and unprotected receptive and insertive anal sex with HIV infected partners and partners with unknown HIV status. NPEP use was also associated with use of illicit drugs (injection drugs, crack cocaine, hallucinogens, and amphetamines). Importantly, willingness to use nPEP after high risk sex was associated with lower odds of high risk sex. After an episode of nPEP use, nPEP users remained more likely to report high risk sex than those in this cohort who had not previously used nPEP. However, within the subset of people who had previously reported high risk sex, previous nPEP use was not associated with higher odds of high risk sex, thus allaying fears that availability of nPEP would lead to an increase in high risk sex.

Background: Two trials were conducted to compare emergency department patient comprehension of rapid HIV pre-test information using different methods to deliver this information. Methods: Patients were enrolled for these two trials at a US emergency department between February 2005 and January 2006. In Trial One, patients were randomized to a no pre-test information or an in-person discussion arm. In Trial Two, a separate group of patients were randomized to an in-person discussion arm or a Tablet PC-based video arm. The video, "Do you know about rapid HIV testing?," and the in-person discussion contained identical Centers for Disease Control and Prevention-suggested pre-test information components as well as information on rapid HIV testing with OraQuick®. Participants were compared by information arm on their comprehension of the pre-test information by their score on a 26-item questionnaire using the Wilcoxon rank-sum test. Results: In Trial One, 38 patients completed the no-information arm and 31 completed the in-person discussion arm. Of these 69 patients, 63.8% had twelve years or fewer of formal education and 66.7% had previously been tested for HIV. The mean score on the questionnaire for the in-person discussion arm was higher than for the no information arm (18.7 vs. 13.3, p ≤ 0.0001). In Trial Two, 59 patients completed the in-person discussion and 55 completed the video arms. Of these 114 patients, 50.9% had twelve years or fewer of formal education and 68.4% had previously been tested for HIV. The mean score on the questionnaire for the video arm was similar to the in-person discussion arm (20.0 vs. 19.2; p ≤ 0.33). Conclusion: The video "Do you know about rapid HIV testing?" appears to be an acceptable substitute for an in-person pre-test discussion on rapid HIV testing with OraQuick®. In terms of adequately informing ED patients about rapid HIV testing, either form of pre-test information is preferable than for patients to receive no pre-test information.

History of Science

The effectiveness of a mandatory premarital screening program was examined as a means of curtailing the spread of the human immunodeficiency virus (HIV) infection in the United States. The epidemiology of the HIV, the technical characteristics of tests for antibodies to HIV, and the logistic, economic, and legal implications of such a program were considered. In one year, universal premarital screening in the United States currently would detect fewer than one tenth of 1% of HIV-infected individuals at a cost of substantially more than $100 million. More than 100 infected individuals would be told that they were probably not infected, and there would likely be more than 350 false-positive results. Public education, counseling of individuals, and discretionary testing can be important tools in reducing the spread of HIV infection, but mandatory premarital screening in a population with a low prevalence of infection is a relatively ineffective and inefficient use of resources., History of Science