Abstract: OBJECTIVE: Substantial country-level variation exists in prejudiced attitudes towards male homosexuality and in the extent to which countries promote the unequal treatment of MSM through discriminatory laws. The impact and underlying mechanisms of country-level stigma on odds of diagnosed HIV, sexual opportunities, and experience of HIV-prevention services, needs and behaviours have rarely been examined, however. DESIGN: Data come from the European MSM Internet Survey (EMIS), which was administered between June and August 2010 across 38 European countries (N = 174 209). METHODS: Country-level stigma was assessed using a combination of national laws and policies affecting sexual minorities and a measure of attitudes held by the citizens of each country. We also assessed concealment, HIV status, number of past 12-month male sex partners, and eight HIV-preventive services, knowledge, and behavioural outcomes. RESULTS: MSM living in countries with higher levels of stigma had reduced odds of diagnosed HIV and fewer partners but higher odds of sexual risk behaviour, unmet prevention needs, not using testing services, and not discussing their sexuality in testing services. Sexual orientation concealment mediated associations between country-level stigma and these outcomes. CONCLUSION: Country-level stigma may have historically limited HIV transmission opportunities among MSM, but by restricting MSM's public visibility, it also reduces MSM's ability to access HIV-preventive services, knowledge and precautionary behaviours. These findings suggest that MSM in European countries with high levels of stigma are vulnerable to HIV infection. Although they have less opportunity to identify and contact other MSM, this might change with emerging technologies.

Abstract: OBJECTIVE HIV-1 infection is characterized by altered intestinal barrier, gut microbiota dysbiosis, and systemic inflammation. We hypothesized that changes of the gut microbiota predict immune dysfunction and HIV-1 progression, and that antiretroviral therapy (ART) partially restores the microbiota composition. DESIGN An observational study including 28 viremic patients, three elite controllers, and nine uninfected controls. Blood and stool samples were collected at baseline and for 19 individuals at follow-up (median 10 months) during ART. METHODS Microbiota composition was determined by 16S rRNA sequencing (Illumina MiSeq). Soluble markers of microbial translocation and monocyte activation were analyzed by Limulus Amebocyte Lysate assay or ELISA. RESULTS Several alpha-diversity measures, including number of observed bacterial species and Shannon index, were significantly lower in viremic patients compared to controls. The alpha diversity correlated with CD4 T-cell counts and inversely with markers of microbial translocation and monocyte activation. In multivariate linear regression, for every age and sex-adjusted increase in the number of bacterial species, the CD4 T-cell count increased with 0.88 (95% confidence interval 0.35-1.41) cells/μl (P = 0.002). After introduction of ART, microbiota alterations persisted with further reduction in alpha diversity. The microbiota composition at the genus level was profoundly altered in viremic patients, both at baseline and after ART, with Prevotella reduced during ART (P < 0.007). CONCLUSIONS Gut microbiota alterations are closely associated with immune dysfunction in HIV-1 patients, and these changes persist during short-term ART. Our data implicate that re-shaping the microbiota may be an adjuvant therapy in patients commencing successful ART.

Abstract: Clinical trial data have shown that oral pre-exposure prophylaxis (PrEP) is efficacious when taken as prescribed; however, PrEP adherence is complex and must be understood within the context of variable risk for HIV infection and use of other HIV prevention methods. Different levels of adherence may be needed in different populations to achieve HIV prevention, and the optimal methods for achieving the necessary adherence for both individual and public health benefits are unknown. Guidance for PrEP use must consider these questions to determine the success of PrEP-based HIV prevention programs. In this article, we propose a new paradigm for understanding and measuring PrEP adherence, termed prevention-effective adherence, which incorporates dynamic HIV acquisition risk behaviors and the use of HIV alternative prevention strategies. We discuss the need for daily PrEP use only during periods of risk for HIV exposure, describe key issues for measuring and understanding relevant behaviors, review lessons from another health prevention field (i.e., family planning), and provide guidance for prevention-effective PrEP use. Moreover, we challenge emerging calls for sustained, near perfect PrEP adherence regardless of risk exposure and offer a more practical and public health-focused vision for this prevention intervention.

Abstract: Background: Cardiovascular disease and non-AIDS malignancies have become major causes of death among HIV-infected individuals. The relative impact of lifestyle and HIV-related factors are debated. Methods: We estimated associations of smoking with mortality more than 1 year after antiretroviral therapy (ART) initiation among HIV-infected individuals enrolled in European and North American cohorts. IDUs were excluded. Causes of death were assigned using standardized procedures. We used abridged life tables to estimate life expectancies. Life-years lost to HIV were estimated by comparison with the French background population. Results: Among 17995 HIV-infected individuals followed for 79760 person-years, the proportion of smokers was 60%. The mortality rate ratio (MRR) comparing smokers with nonsmokers was 1.94 [95% confidence interval (95% CI) 1.56‐2.41]. The MRRs comparing current and previous smokers with never smokers were 1.70 (95% CI 1.23‐2.34) and 0.92 (95% CI 0.64‐1.34), respectively. Smokers had substantially higher mortality from cardiovascular disease, non-AIDS malignancies than nonsmokers [MRR 6.28 (95% CI 2.19‐18.0) and 2.67 (95% CI 1.60‐4.46), respectively]. Among 35-year-old HIV-infected men, the loss of life-years associated with smoking and HIV was 7.9 (95% CI 7.1‐8.7) and 5.9 (95% CI 4.9‐ 6.9), respectively. The life expectancy of virally suppressed, never-smokers was 43.5 years (95% CI 41.7‐45.3), compared with 44.4 years among 35-year-old men in the background population. Excess MRRs/1000 person-years associated with smoking increased from 0.6 (95% CI ‐1.3 to 2.6) at age 35 to 43.6 (95% CI 37.9‐49.3) at age at least 65 years. Conclusion: Well treated HIV-infected individuals may lose more life years through smoking than through HIV. Excess mortality associated with smoking increases markedly with age. Therefore, increases in smoking-related mortality can be

Abstract: OBJECTIVE: We aimed to estimate the odds of engagement in HIV care and treatment among HIV-positive women reporting intimate partner violence (IPV). DESIGN: We systematically reviewed the literature on the association between IPV and engagement in care. Data sources included searches of electronic databases (PubMed, Web of Science, CINAHL and PsychoInfo), hand searches and citation tracking. METHODS: Two reviewers screened 757 full-text articles, extracted data and independently appraised study quality. Included studies were peer-reviewed and assessed IPV alongside engagement in care outcomes: antiretroviral treatment (ART) use; self-reported ART adherence; viral suppression; retention in HIV care. Odds ratios (ORs) were pooled using random effects meta-analysis. RESULTS: Thirteen cross-sectional studies among HIV-positive women were included. Measurement of IPV varied, with most studies defining a 'case' as any history of physical and/or sexual IPV. Meta-analysis of five studies showed IPV to be significantly associated with lower ART use [OR 0.79, 95% confidence interval (95% CI) 0.64-0.97]. IPV was associated with poorer self-reported ART adherence in seven studies (OR 0.48, 95% CI 0.30-0.75) and lower odds of viral load suppression in seven studies (OR 0.64, 95% CI 0.46-0.90). Lack of longitudinal data and measurement considerations should temper interpretation of these results. CONCLUSION: IPV is associated with lower ART use, half the odds of self-reported ART adherence and significantly worsened viral suppression among women. To ensure the health of HIV-positive women, it is essential for clinical programmes to address conditions that impact engagement in care and treatment. IPV is one such condition, and its association with declines in ART use and adherence requires urgent attention. Language: en

Abstract: Objective:The epidemiology of the incidence of sexually transmitted hepatitis C virus (HCV) infection in HIV-positive men who have sex with men (MSM) is only partially understood. In the presence of HIV, HCV infection is more likely to become chronic and liver fibrosis progression is accelerated.Des

Abstract: Soluble CD14 is associated with morbidity and mortality in HIV disease. It is a co-receptor for lipopolysaccharide (LPS) that is released from monocytes upon activation. We demonstrate here, that inflammatory cytokines can induce the release of sCD14 in peripheral blood mononuclear cell cultures from healthy donors, and that TLR ligands other than LPS can cause a decrease in the monocyte cell surface expression of CD14. Thus, sCD14 is a marker of monocyte activation, not restricted to activation by LPS.

Abstract: Author(s): Somsouk, Ma; Estes, Jacob D; Deleage, Claire; Dunham, Richard M; Albright, Rebecca; Inadomi, John M; Martin, Jeffrey N; Deeks, Steven G; McCune, Joseph M; Hunt, Peter W | Abstract: ObjectiveMicrobial translocation and innate immune action characterize HIV infection. Continued gut mucosal dysfunction during treatment and its relationship to CD4 T-cell recovery has not been well described.DesignA cross-sectional study was performed of antiretroviral therapy (ART)-suppressed (immunologic responders with CD4 g 500 cells/μl and immunologic nonresponders with CD4 l 350 cells/μl), untreated HIV-infected, and seronegative participants consenting to gut biopsies and a blood draw.MethodsNeutrophil infiltration as a surrogate response to epithelial breach, colorectal epithelial proliferation as a measure of repair, and mucosal apoptosis by immunohistochemistry were determined in gut biopsies. Plasma markers of monocyte activation (sCD14), immune activation (interleukin-6), and indoleamine 2,3-dioxygenase-1 activity (plasma kynurenine/tryptophanratio) were concurrently measured.ResultsEach HIV-infected group had greater neutrophil infiltration than controls. Similarly, untreated HIV-infected participants and ART-suppressed immunologic responders had increased epithelial proliferation compared with controls, but immunologic nonresponders had no appreciable increase in epithelial proliferation despite elevated neutrophil infiltration. The CD4 T-cell count was positively correlated with epithelial proliferation and was modestly negatively correlated with neutrophil infiltration in ART-suppressed patients. Epithelial proliferation was inversely correlated with mucosal apoptosis, and apoptosis was linked to plasma sCD14 and modestly to kynurenine/tryptophan ratio.ConclusionsNeutrophil infiltration and mucosal apoptosis remain abnormally high despite ART. Epithelial proliferation increases in HIV, but may be impaired in immunologic nonresponders. Whether mucosal apoptosis is a cause or consequence of epithelial proliferative defects is unclear, but appears to be associated with systemic inflammation. The impact of ART and interventions targeting the gut epithelial barrier in treated HIV infection warrant further investigation.

Abstract: Objectives Aging with HIV is associated with multisystem vulnerability that might be well characterized by frailty. We sought to construct a frailty index based on health deficit accumulation in a large HIV clinical cohort and evaluate its validity including the ability to predict mortality and incident multimorbidity. Design and methods This is an analysis of data from the prospective Modena HIV Metabolic Clinic cohort, 2004-2014. Routine health variables were screened for potential inclusion in a frailty index. Content, construct, and criterion validity of the frailty index were assessed. Multivariable regression models were built to investigate the ability of the frailty index to predict survival and incident multimorbidity (at least two chronic disease diagnoses) after adjusting for known HIV-related and behavioral factors. Results Two thousand, seven hundred and twenty participants (mean age 46 ± 8; 32% women) provided 9784 study visits; 37 non-HIV-related variables were included in a frailty index. The frailty index exhibited expected characteristics and met validation criteria. Predictors of survival were frailty index (0.1 increment, adjusted hazard ratio 1.63, 95% confidence interval 1.05-2.52), current CD4 cell count (0.48, 0.32-0.72), and injection drug use (2.51, 1.16-5.44). Predictors of incident multimorbidity were frailty index (adjusted incident rate ratio 1.98, 1.65-2.36), age (1.07, 1.05-1.09), female sex (0.61, 0.40-0.91), and current CD4 cell count (0.71, 0.59-0.85). Conclusion Among people aging with HIV in northern Italy, a frailty index based on deficit accumulation predicted survival and incident multimorbidity independently of HIV-related and behavioral risk factors. The frailty index holds potential value in quantifying vulnerability among people aging with HIV.

Abstract: Per year, there are approximately 50,000 HIV infection in the United States[1], and the HIV epidemic continues to disproportionately affect the lives of men who have sex with men (MSM). Public health researchers and practitioners have increasingly highlighted the importance of structural determinants on the HIV epidemic, building on a long tradition of research and practice in social and behavioral sciences. Although scientific advances have demonstrated the efficacy of biomedical HIV prevention interventions, including pre- and post-exposure prophylaxis (PrEP and PEP, respectively), to protect against HIV transmission,[2–4] social contexts affect environments in which people live and can present barriers to implementation and adherence to this individual-level intervention.[5–9] The effectiveness of both PEP and PrEP is highly correlated with adherence to the regimen.[2,3,10,11] Psychosocial processes such as depression adversely affect adherence to antiretroviral therapy,[12] and macro-level environments strongly influence these psychosocial factors.[9,13] Given the recent shifts in state-level policies to protect sexual minorities in the United States[14], further research into the impact of the social environment on the awareness and acceptability of prevention tools, such as PrEP, is a critical area for public health today. Recently, research among sexual minority populations has increasingly considered the role of stigma related to sexual orientation at the individual, interpersonal and structural level in affecting risk for adverse health outcomes.[15,16] Stigma is broadly defined as negative attitudes, relative powerlessness, and loss of status related to a particular characteristic.[17,18] Experiences of stigma can occur at the individual (i.e., self-stigma), interpersonal (i.e., enacted or experienced stigma), and structural [16] levels. Structural stigma related to sexual orientation (henceforth, “structural stigma”) has been defined as “societal-level conditions, cultural norms, and institutional policies and practices that constrain the opportunities, resources, and wellbeing of the stigmatized”.[19] Among MSM, individual and interpersonal forms of stigma have been associated with decreased access to healthcare in diverse settings[20,21], with increased HIV risk, and adverse mental health conditions.[22–24] However, few empirical investigations have investigated the relationship between structural stigma and HIV prevention among MSM. To address this gap, we conducted an online survey of MSM in the United States that was designed to assess sexual behaviors, awareness and use of PEP and PrEP, and comfort with primary care providers. We hypothesized that individuals living in areas with higher structural stigma (increased anti-gay prejudicial social environments at the state level) would have decreased awareness and utilization of PEP and PrEP, decreased condom use, and reduced ability to discuss sexual risk and HIV prevention strategies with primary care providers.

Abstract: OBJECTIVES The objective of this study is to determine associations between intertwining epidemics (syndemics) and HIV medication adherence and viral load levels among HIV-positive MSM and to test whether adherence mediates the relationship between syndemics and viral load. DESIGN We analysed participant data collected between 2003 and 2009 from the Multicenter AIDS Cohort Study, a prospective HIV/AIDS cohort study in four U.S. cities. METHODS We conducted longitudinal analyses (repeated measures mixed models) to assess whether differences in viral load levels, undetectable viral load and self-reported HIV medication adherence were associated with count of syndemic conditions (substance use, depression symptoms and sexual risk behaviour, range 0-3), adjusting for race/ethnicity, age and income. Mediation analyses were conducted using structural equation modelling and the SAS %mediate macro. RESULTS Syndemics count was associated with higher viral loads (P < 0.0001) and lower adherence (P < 0.0001). Increased counts of concomitant syndemics were associated with viral load (P < 0.01), detectable viral load (P < 0.05) and adherence (P < 0.001). Black MSM experienced worse outcomes across domains than white MSM (P < 0.0001) and experienced higher overall rates of syndemics (P < 0.01). Adherence significantly mediated the relationship between syndemics and viral load, accounting for an estimated 32.3% of the effect (P < 0.05). CONCLUSION Effectively lowering viral load levels among MSM has implications for both HIV/AIDS prevention and care. Our findings suggest that integrating substance use interventions, mental healthcare and sexual risk prevention into standard HIV care may be necessary to optimize treatment and Treatment as Prevention (TasP) models.

Abstract: Women are frequently depicted as the face of AIDS in sub-Saharan Africa (SAA) [1–3] where they comprise nearly 58% of all reported HIV infections [4]. Donor dollars, policies, and HIV programs have followed suit, resulting in a near-exclusive focus on women [e.g. 5]. Although African women are represented as particularly vulnerable to HIV infection [6], it is men, not women, who are more likely to die of AIDS [7–9]. AIDS prevalence may have the face of a woman, but AIDS mortality has the face of a man.

Abstract: Objective The objective of this study is to determine whether adipose tissue functions as a reservoir for HIV-1. Design We examined memory CD4(+) T cells and HIV DNA in adipose tissue-stromal vascular fraction (AT-SVF) of five patients [four antiretroviral therapy (ART)-treated and one untreated]. To determine whether adipocytes stimulate CD4(+) T cells and regulate HIV production, primary human adipose cells were cocultured with HIV-infected CD4(+) T cells. Methods AT-SVF T cells were studied by flow cytometry, and AT-SVF HIV DNA (Gag and Env) was examined by nested PCR and sequence analyses. CD4(+) T-cell activation and HIV production were measured by flow cytometry and ELISA. Results AT-SVF CD3(+) T cells were activated (>60% CD69(+)) memory CD4(+) and CD8(+) T cells in uninfected and HIV-infected persons, but the AT-SVF CD4(+)/CD8(+) ratio was lower in HIV patients. HIV DNA (Gag and Env) was detected in AT-SVF of all five patients examined by nested PCR, comparably to other tissues [peripheral blood mononuclear cell (PBMC), lymph node or thymus]. In coculture experiments, adipocytes increased CD4(+) T-cell activation and HIV production approximately two to three-fold in synergy with gamma-chain cytokines interleukin (IL)-2, IL7 or IL15. These effects were mitigated by neutralizing antibodies against IL6 and integrin-α1β1. Adipocytes also enhanced T-cell viability. Conclusion Adipose tissues of ART-treated patients harbour activated memory CD4(+) T cells and HIV DNA. Adipocytes promote CD4(+) T-cell activation and HIV production in concert with intrinsic adipose factors. Adipose tissue may be an important reservoir for HIV.

Abstract: OBJECTIVES: WHO guidelines recommend disclosure to HIV-positive children by school age in order to improve antiretroviral therapy (ART) adherence. However quantitative evidence remains limited for adolescents. This study examines associations between adolescent knowledge of HIV-positive status and ART-adherence in South Africa. DESIGN: A cross-sectional study of the largest known community-traced sample of HIV-positive adolescents. Six hundred and eighty-four ART-initiated adolescents aged 10-19 years (52% female 79% perinatally infected) were interviewed. METHODS: In a low-resource health district all adolescents who had ever initiated ART in a stratified sample of 39 health facilities were identified and traced to 150 communities [n = 1102 351 excluded 27 deceased 40 (5.5%) refusals]. Quantitative interviews used standardized questionnaires and clinic records. Quantitative analyses used multivariate logistic regressions and qualitative analyses used grounded theory for 18 months of interviews focus groups and participant observations with 64 adolescents caregivers and healthcare workers. RESULTS: About 36% of adolescents reported past-week ART nonadherence and 70% of adolescents knew their status. Adherence was associated with fewer opportunistic infection symptoms [odds ratio (OR) 0.55; 95% CI 0.40-0.76]. Adolescent knowledge of HIV-positive status was associated with higher adherence independently of all cofactors (OR 2.18; 95% CI 1.47-3.24). Among perinatally infected adolescents who knew their status (n = 362/540) disclosure prior to age 12 was associated with higher adherence (OR 2.65; 95% CI 1.34-5.22). Qualitative findings suggested that disclosure was undertaken sensitively in clinical and family settings but that adults lacked awareness about adolescent understandings of HIV status. CONCLUSION: Early and full disclosure is strongly associated with improved adherence amongst ART-initiated adolescents. Disclosure may be an essential tool in improving adolescent adherence and reducing mortality and onwards transmission.

Abstract: Use of 'party drugs', a particular set of recreational drugs used in the context of 'ChemSex', is frequent among MSM living with HIV. A recently published observational study showed that more than half of HIV-infected MSM interviewed reported use of illicit substances in the previous 3 months, with frequent concomitant use of three or more drugs. These substances are a combination of 'club drugs' (methylenedioxymethamphetamine, gamma-hydroxybutyrate, ketamine, benzodiazepine) and drugs that are more specifically used in a sexualized context (methamphetamine, mephedrone, poppers and erectile dysfunction agents). Although formal data on pharmacokinetic or pharmacodynamic interactions between recreational drugs and antiretroviral agents are lacking, information regarding potentially toxic interactions can be theorized or sometimes conclusions may be drawn from case studies and cohort observational studies. However, the risk of coadministering party drugs and antiretrovirals should not be overestimated. The major risk for a drug-drug interaction is when using ritonavir-boosting or cobicistat-boosting agents, and maybe some nonnucleoside reverse transcriptase inhibitors. Knowledge of the metabolic pathways of 'party drugs' may help in advising patients on which illicit substances have a high potential for drug-drug interactions, as this is not the case for all.

Abstract: Objective HIV-infected people are at increased risk of cancers of infectious origin. We estimated the burden of cancer attributable to infections among HIV-infected people in the United States in 2008. Design Incidence rates for cancer sites associated with infections were estimated from record linkage between HIV/AIDS registries and cancer registries. Methods Rates were applied to estimates of the population living with diagnosed HIV in the United States in 2008 to obtain the number of incident cancer cases. Site-specific attributable fractions and corresponding 95% confidence intervals (CIs) were estimated from infection prevalence among cancer cases. Infection prevalence data were derived from literature review of case series. Results Of an estimated 6200 incident cancer cases (95% CI 6000-6500), 2500 (95% CI 2400-2700) were attributable to infection (attributable fraction = 40%, 95% CI 39-42). The most important infections were Kaposi sarcoma herpes virus, Epstein-Barr virus, and human papillomavirus, which together were responsible for 2200 new cancer cases (95% CI 2100-2400), mainly Kaposi sarcoma, lymphomas, and ano-genital cancers. The attributable fraction in HIV-infected people was highest in the age group 20-29 years (69%, 95% CI 65-72). MSM were the HIV transmission group with the highest attributable fraction (48%, 95% CI 46-50), due to the high incidence of both Kaposi sarcoma and anal cancer. Conclusion The very high fraction of cancer attributable to infection in HIV-infected people points to special opportunities to prevent these cancers, that is, avoidance, detection, and early treatment of cancer-associated infections, and universal early detection and uninterrupted treatment of HIV infection to avoid immunosuppression.

Abstract: Objective The objective of this study is to determine the incidence rate and risk factors of tuberculosis (TB) among HIV-infected adults accessing antiretroviral therapy (ART) in Tanzania. Design A prospective observational study among HIV-infected adults attending HIV clinics in Dar es Salaam. Methods We estimated TB incidence rates among HIV-infected patients prior to and after ART initiation. We used Cox proportional hazard regressions to determine the predictors of incident TB among HIV-infected adults enrolled in the HIV care and treatment programme. Results We assessed 67 686 patients for a median follow-up period of 24 (interquartile range: 8-49) months; 7602 patients were diagnosed with active TB. The TB incidence rate was 7.9 [95% confidence interval (95% CI), 7.6-8.2] per 100 person-years prior to ART initiation, and 4.4 (95% CI, 4.2-4.4) per 100 person-years for patients receiving ART. In multivariate analyses, patients on ART in the first 3 months had a 57% higher risk of TB (hazard ratio: 1.57, 95% CI, 1.47-1.68) than those not on ART, but the risk significantly decreased with increasing duration of ART. Risk factors for incident TB included being male, having low BMI or middle upper arm circumference, lower CD4 cell count and advanced WHO disease stage. There was seasonal variation for incident TB, with higher risk observed following the rainy seasons (May, June and November). Conclusion In TB endemic regions, HIV-infected patients initiating ART, particularly men and those with poor nutritional status, should be closely monitored for active TB at ART initiation. In addition to increasing the access to ART, interventions should be considered to improve nutritional status among HIV-infected patients.

Abstract: Objectives Mental health conditions can erode quality of life and interfere with health-related behaviours such as medication adherence. We aimed to determine the prevalence and correlates of depression and other psychosocial factors among self-identified men who have sex with men (MSM) in coastal Kenya. Design A cross-sectional survey. Methods Psychosocial and mental health characteristics were assessed in an audio computer-assisted self-interview (ACASI) survey among 112 MSM participating in two ongoing HIV-positive and HIV-negative cohorts in Mtwapa, Kenya. Results One-third of participants met criteria for major depressive disorder [16.1%, 95% confidence interval (95% CI) 9.8-24.2] or other depressive disorder (15.2%, 95% CI 9.1-23.2). Alcohol abuse was reported by 45% of respondents (95% CI 35.2-54.3) and other substance abuse by 59.8% (95% CI 50.1-69.0). Sexual and HIV stigma were moderate, with median scores of 11 [interquartile range (IQR) 6-17, potential range 0-33] and 25 (IQR 23-29, potential range 11-44), respectively. There were significant bivariate correlations between alcohol abuse, other substance abuse, sexual stigma and childhood and recent abuse. In a multivariable linear regression model, sexual stigma (beta = 0.17, 95% CI 0.03-0.32) and marriage to a woman (beta = -2.41 95% CI -4.74 to -0.09) were each associated with depression score. Conclusion We found moderate to high levels of depression and substance abuse, and moderate levels of sexual stigma. These variables were highly inter-correlated and associated with an experience of trauma or abuse. Comprehensive mental health services are needed in this population to address these issues.

Abstract: OBJECTIVE The objective of this study is to assess whether multivariate normative comparison (MNC) improves detection of HIV-1-associated neurocognitive disorder (HAND) as compared with Frascati and Gisslen criteria. METHODS One-hundred and three HIV-1-infected men with suppressed viremia on combination antiretroviral therapy (cART) for at least 12 months and 74 HIV-uninfected male controls (comparable regarding age, ethnicity, sexual orientation, premorbid intelligence and educational level), aged at least 45 years, underwent neuropsychological assessment covering six cognitive domains (fluency, attention, information processing speed, executive function, memory, and motor function). Frascati and Gisslen criteria were applied to detect HAND. Next, MNC was performed to compare the cognitive scores of each HIV-positive individual against the cognitive scores of the control group. RESULTS HIV-infected men showed significantly worse performance on the cognitive domains of attention, information processing speed and executive function compared with HIV-uninfected controls. HAND by Frascati criteria was highly prevalent in HIV-infected [48%; 95% confidence interval (95% CI) 38-58] but nearly equally so in HIV-uninfected men (36%; 95% CI 26-48), confirming the low specificity of this method. Applying Gisslen criteria, HAND-prevalence was reduced to 5% (95% CI 1-9) in HIV-infected men and to 1% (95% CI 1-3) among HIV-uninfected controls, indicating better specificity but reduced sensitivity. MNC identified cognitive impairment in 17% (95% CI 10-24) of HIV-infected men and in 5% (95% CI 0-10) of the control group (P = 0.02, one-tailed), showing an optimal balance between sensitivity and specificity. CONCLUSION Prevalence of cognitive impairment in HIV-1-infected men with suppressed viremia on cART estimated by MNC was much higher than that estimated by Gisslen criteria, while the false positive rate was greatly reduced compared with the Frascati criteria. VIDEO ABSTRACT :

Abstract: Objective To estimate the association of age of viral suppression and central nervous system penetration effectiveness (CPE) score with neurocognitive functioning among school-age children with perinatally-acquired HIV infection (PHIV+).

Abstract: BACKGROUND The goal of antiretroviral therapy (ART) is to reduce HIV-related morbidity and mortality by suppressing HIV replication. The prognostic value of persistent low-level viremia (LLV), particularly for clinical outcomes, is unknown. OBJECTIVE Assess the association of different levels of LLV with virological failure, AIDS event, and death among HIV-infected patients receiving combination ART. METHODS We analyzed data from 18 cohorts in Europe and North America, contributing to the ART Cohort Collaboration. Eligible patients achieved viral load below 50 copies/ml within 3-9 months after ART initiation. LLV50-199 was defined as two consecutive viral loads between 50 and 199 copies/ml and LLV200-499 as two consecutive viral loads between 50 and 499 copies/ml, with at least one between 200 and 499 copies/ml. We used Cox models to estimate the association of LLV with virological failure (two consecutive viral loads at least 500 copies/ml or one viral load at least 500 copies/ml, followed by a modification of ART) and AIDS event/death. RESULTS Among 17 902 patients, 624 (3.5%) experienced LLV50-199 and 482 (2.7%) LLV200-499. Median follow-up was 2.3 and 3.1 years for virological and clinical outcomes, respectively. There were 1903 virological failure, 532 AIDS events and 480 deaths. LLV200-499 was strongly associated with virological failure [adjusted hazard ratio (aHR) 3.97, 95% confidence interval (CI) 3.05-5.17]. LLV50-199 was weakly associated with virological failure (aHR 1.38, 95% CI 0.96-2.00). LLV50-199 and LLV200-499 were not associated with AIDS event/death (aHR 1.13, 95% CI 0.81-1.68; and aHR 0.95, 95% CI 0.62-1.48, [corrected] respectively). CONCLUSION LLV200-499 was strongly associated with virological failure, but not with AIDS event/death. Our results support the US guidelines, which define virological failure as a confirmed viral load above 200 copies/ml.

Abstract: OBJECTIVE The main aim of this study was to determine whether HIV replication can be controlled following interruption of treatment started early in the course of infection (CD4 >350 cells/μl and viral load <50 000 copies/ml), but not during the primary infection. METHODS Patients enrolled in a multicenter trial of treatment interruption (ANRS 116 SALTO) with CD4 above 450 cells/μl and viral load below 400 copies/ml at treatment interruption were selected for this second analysis. We determined the proportion of patients whose plasma HIV-RNA load remained below 400 copies/ml during the first 12 months of treatment interruption, and baseline factors predictive of time to loss of viral control. Viral load rebound was defined as two successive values above 400 copies/ml, or as one value above 400 copies/ml, followed by treatment resumption. RESULTS We studied 95 patients with a median CD4 nadir of 382 cells/μl (340-492). At treatment interruption, the median CD4 cell count and HIV-DNA load were 813/μl (695-988) and 206 copies/10 peripheral blood mononuclear cells (PBMCs) (53-556). Twelve months after treatment interruption, seven patients still had viral load below 400 copies/ml (Kaplan-Meier estimate 7.5%, 95% confidence interval 3.7-14.6), and four of them still had viral load below 400 copies/ml at 36 months. A multivariable Cox proportional-hazards model showed that time to loss of viral control was more shorter in patients with HIV-DNA at least 150 copies/10 PBMCs at treatment interruption (hazard ratio 2.1, 95% confidence interval 1.3-3.3, P = 0.002) than in those with HIV-DNA below 150 copies/10 PBMCs. CONCLUSION Patients who have low HIV-DNA levels at antiretroviral treatment interruption are more likely to maintain viral control for long periods.

Abstract: OBJECTIVE Determine whether HIV and combination antiretroviral therapy (cART) affect resting-state functional connectivity (rs-fc) between the striatum and the cortical regions. METHODS Forty-nine HIV-uninfected (HIV-) and 132 HIV-infected (HIV+) (65% receiving cART) patients underwent laboratory studies (current and nadir CD4 T-cell counts, and plasma HIV viral load), neuropsychological performance testing, and neuroimaging. Rs-fc, which examines the coordination of neural activity in distant brain regions, was used to investigate the cortico-striatal functional connections. The effect of cART was assessed comparing HIV+ individuals on cART (HIV+/cART+), and HIV+ individuals not currently receiving cART (HIV+/cART-). Relationships between laboratory tests, cognitive performance, and cART on subcortical-cortical rs-fc were assessed by an analysis of variance. RESULTS HIV+ individuals had lower cortico-striatal functional connectivity than HIV- controls, specifically between the striatum and the default mode network (P < 0.001) and ventral attention network (P < 0.001). HIV+/cART+ individuals had higher functional connectivity between the striatum, and default mode network (P = 0.02) and ventral attention network (P = 0.01), compared to the HIV+/cART- patients. Laboratory (current and nadir CD4 T-cell counts, plasma viral load) and neuropsychological performance was not correlated with cortico-striatal rs-fc. CONCLUSIONS HIV was associated with disrupted cortico-striatal networks, consistent with HIV's known impact on the subcortical areas. Interestingly, within certain networks, HIV+/cART+ individuals had similar rs-fc compared to HIV- controls, suggesting possible improvements in HIV-related neural dysfunction due to medications. Rs-fc may be a sensitive biomarker of neural insult and its recovery following cART. Additional studies may show rs-fc has utility in measuring acute inflammation caused by HIV.

Abstract: OBJECTIVE: To characterize prevalence incidence and associated correlates of HIV infection among MSM in 12 cities across India. DESIGN: Cross-sectional sample using respondent-driven sampling from September 2012 to June 2013. METHODS: A total 12022 MSM (~1000/city) were recruited. Participants had to be at least 18 years self-identify as male and report oral/anal intercourse with a man in the prior year. HIV infection was diagnosed using three rapid tests. Cross-sectional HIV incidence was estimated using a multiassay algorithm. All estimates incorporate respondent-driven sampling-II weights. RESULTS: Median age was 25 years 45% self-identified as panthi (predominantly penetrative anal intercourse) and 30.6% reported being married to a woman. Weighted HIV prevalence was 7.0% (range: 1.7-13.1%). In multivariate analysis significantly higher odds of HIV infection was observed among those who were older had lower educational attainment were practicing purely receptive anal sex or both receptive and penetrative sex and those who were herpes simplex virus-2 positive. Of 1147 MSM who tested HIV positive 53 were identified as recent HIV infections (annualized incidence = 0.87%; range = 0-2.2%). In multivariate analysis injecting drugs in the prior 6 months syphilis and higher number of male partners and fewer female partners were significantly associated with recent HIV infection. CONCLUSION: We observed a high burden of HIV among MSM in India with tremendous diversity in prevalence incidence and risk behaviors. In particular we observed high incidence in areas with relatively low prevalence suggesting emerging epidemics in areas not previously recognized to have high HIV burden.

Abstract: OBJECTIVES To evaluate the impact of liver and kidney transplantation on survival in HIV-positive transplant candidates and compare outcomes between HIV-positive and negative recipients. DESIGN Observational cohort of HIV-positive transplant candidates and recipients and secondary analysis comparing study recipients to HIV-negative national registry controls. METHODS We fit proportional hazards models to assess transplantation impact on mortality among recipients and candidates. We compared time to graft failure and death with HIV-negative controls in unmatched, demographic-matched, and risk-adjusted models. RESULTS There were 17 (11.3%) and 46 (36.8%) deaths among kidney and liver recipients during a median follow-up of 4.0 and 3.5 years, respectively. Transplantation was associated with survival benefit for HIV-infected liver recipients with model for end-stage liver disease (MELD) greater than or equal 15 [hazard ratio (HR) 0.1; 95% confidence interval (CI) 0.05, 0.01; P < 0.0001], but not for MELD less than 15 (HR 0.7; 95% CI 0.3, 1.8; P = 0.43) or for kidney recipients (HR 0.6; 95% CI 0.3, 1.4; P = 0.23). In HIV-positive kidney recipients, unmatched and risk-matched analyses indicated a marginally significant HR for graft loss [1.3 (P = 0.07) and HR 1.4 (P = 0.052)]; no significant increase in risk of death was observed. All models demonstrated a higher relative hazard of graft loss or death in HIV-positive liver recipients; the absolute difference in the proportion of deaths was 6.7% in the risk-matched analysis. CONCLUSION Kidney transplantation should be standard of care for well managed HIV-positive patients. Liver transplant in candidates with high MELD confers survival benefit; transplant is a viable option in selected candidates. The increased mortality risk compared with HIV-negative recipients was modest. TRIAL REGISTRATION ClinicalTrials.Gov; NCT00074386; http://clinicaltrials.gov/.

Abstract: OBJECTIVES Food insecurity and HIV/AIDS outcomes are inextricably linked in sub-Saharan Africa. We report on health and nutritional outcomes of a multisectoral agricultural intervention trial among HIV-infected adults in rural Kenya. DESIGN This is a pilot cluster randomized controlled trial. METHODS The intervention included a human-powered water pump, a microfinance loan to purchase farm commodities, and education in sustainable farming practices and financial management. Two health facilities in Nyanza Region, Kenya were randomly assigned as intervention or control. HIV-infected adults 18 to 49 years' old who were on antiretroviral therapy and had access to surface water and land were enrolled beginning in April 2012 and followed quarterly for 1 year. Data were collected on nutritional parameters, CD4 T-lymphocyte counts, and HIV RNA. Differences in fixed-effects regression models were used to test whether patterns in health outcomes differed over time from baseline between the intervention and control arms. RESULTS We enrolled 72 and 68 participants in the intervention and control groups, respectively. At 12 months follow-up, we found a statistically significant increase in CD4 cell counts (165 cells/μl, P < 0.001) and proportion virologically suppressed in the intervention arm compared with the control arm (comparative improvement in proportion of 0.33 suppressed, odds ratio 7.6, 95% confidence interval: 2.2-26.8). Intervention participants experienced significant improvements in food security (3.6 scale points higher, P < 0.001) and frequency of food consumption (9.4 times per week greater frequency, P = 0.013) compared to controls. CONCLUSION Livelihood interventions may be a promising approach to tackle the intersecting problems of food insecurity, poverty and HIV/AIDS morbidity.

Abstract: OBJECTIVE: Programme implementers have argued that the increasing availability of antiretroviral therapy (ART) will reduce the stigma of HIV. We analyzed data from Uganda to assess how HIV-related stigma has changed during a period of ART expansion. DESIGN: Serial cross-sectional surveys. METHODS: We analyzed data from the Uganda AIDS Rural Treatment Outcomes study during 2007-2012 to estimate trends in internalized stigma among people living with HIV (PLHIV) at the time of treatment initiation. We analyzed data from the Uganda Demographic and Health Surveys from 2006 to 2011 to estimate trends in stigmatizing attitudes and anticipated stigma in the general population. We fitted regression models adjusted for sociodemographic characteristics with year of data collection as the primary explanatory variable. RESULTS: We estimated an upward trend in internalized stigma among PLHIV presenting for treatment initiation [adjusted b = 0.18; 95% confidence interval (CI) 0.06-0.30]. In the general population the odds of reporting anticipated stigma were greater in 2011 compared with 2006 [adjusted odds ratio (OR) = 1.80; 95% CI 1.51-2.13] despite an apparent decline in stigmatizing attitudes (adjusted OR = 0.62; 95% CI 0.52-0.74). CONCLUSION: Internalized stigma has increased over time among PLHIV in the setting of worsening anticipated stigma in the general population. Further study is needed to better understand the reasons for increasing HIV-related stigma in Uganda and its impact on HIV prevention efforts.

Abstract: Objective Some intestinal microbiota-generated metabolites of phosphatidylcholine are recognized to be proatherogenic. As the HIV population is vulnerable to cardiovascular disease and can develop intestinal dysbiosis associated with systemic inflammation, we investigated the novel relationship between microbiota-derived metabolites of phosphatidylcholine and coronary atherosclerosis in HIV. Design/methods One hundred and fifty-five HIV-infected and 67 non-HIV-infected individuals without known history of cardiovascular disease were previously recruited to assess coronary plaque by computed tomography angiography. In the current study, we evaluate whether serum choline, trimethylamine (TMA), or trimethylamine-N-oxide (TMAO) levels are associated with plaque features. Results Young, asymptomatic HIV-infected patients (age 47 ± 7 years) demonstrated significantly higher prevalence of plaque (53 vs. 35%, P = 0.01) and number of total plaque segments (1.8 ± 2.5 vs. 1.2 ± 2.2, P = 0.03) when compared with well matched noninfected individuals with similar comorbidities. TMA was significantly associated with calcium score (r = 0.22, P = 0.006), number of total (r = 0.20, P = 0.02) and calcified (r = 0.18, P = 0.03) plaque segments, and calcium plaque volume (r = 0.19, P = 0.02) and mass (r = 0.22, P = 0.009) in the HIV cohort only. In multivariate modeling among HIV-infected patients, TMA remained significantly associated with calcium score (P = 0.008), number of total (P = 0.005) and calcified (P = 0.02) plaque segments, and calcium plaque volume (P = 0.01) and mass (P = 0.007), independent of Framingham risk score. In contrast, there was no association of TMAO to coronary plaque features in either cohort. Conclusion A link between TMA and atherosclerosis has not previously been established. The current study suggests that TMA may be a nontraditional risk factor related to the number of plaque segments and severity of calcified plaque burden in HIV.

Abstract: Objectives To identify prognostic surrogate markers for change in cognitive states of HIV-infected patients. Design Longitudinal cerebrospinal fluid (CSF) samples were collected from 98 HIV-infected patients identified by temporal change in cognitive states classified as normal, stably impaired, improving and worsening. Methods The metabolic composition of CSF was analysed using H nuclear magnetic resonance (H NMR) spectroscopy that focused on energy metabolites. Metabolic biomarkers for cognitive states were identified using multivariate partial least squares regression modelling of the acquired spectra, combined with nonparametric analyses of metabolites with clinical features. Results Multivariate modelling and cross-validated recursive partitioning identified several energy metabolites that, when combined with clinical variables, classified patients based on change in neurocognitive states. Prognostic identification for worsening was achieved with four features that included no change in a detectable plasma viral load, elevated citrate and acetate; decreased creatine, to produce a model with a predictive accuracy of 92%, sensitivity of 88% and 96% specificity. Prognosis for improvement contained seven features that included first visit age less than 47 years, new or continued use of antiretrovirals, elevated glutamine and glucose; decreased myo-inositol, β-glucose and creatinine to generate a model with a predictive accuracy of 92%, sensitivity of 100% and specificity of 84%. Conclusion These CSF metabolic results suggest that worsening cognitive status in HIV-infected patients is associated with increased aerobic glycolysis, and improvements in cognitive status are associated with a shift to anaerobic glycolysis. Dietary, lifestyle and pharmacologic interventions that promote anaerobic glycolysis could protect the brain in setting of HIV infection with combined antiretroviral therapy.