Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.

Abstractobjectives Non-communicable diseases (NCD) are a growing cause of morbidity in low-income countries including in people living with human immunodeficiency virus (HIV). Integration of NCD and HIV services can build upon experience with chronic care models from HIV programmes. We describe models of NCD and HIV integration, challenges and lessons learned.methods A literature review of published articles on integrated NCD and HIV programs in lowincome countries and key informant interviews were conducted with leaders of identified integrated NCD and HIV programs. Information was synthesised to identify models of NCD and HIV service delivery integration.results Three models of integration were identified as follows: NCD services integrated into centres originally providing HIV care; HIV care integrated into primary health care (PHC) already offering NCD services; and simultaneous introduction of integrated HIV and NCD services. Major challenges identified included NCD supply chain, human resources, referral systems, patient education, stigma, patient records and monitoring and evaluation. The range of HIV and NCD services varied widely within and across models.conclusions Regardless of model of integration, leveraging experience from HIV care models and adapting existing systems and tools is a feasible method to provide efficient care and treatment for the growing numbers of patients with NCDs. Operational research should be conducted to further study how successful models of HIV and NCD integration can be expanded in scope and scaled-up by managers and policymakers seeking to address all the chronic care needs of their patients.

This study explores willingness to use PrEP among Black individuals in the US. From February to April 2016, an online survey was administered to a nationally representative sample of Black individuals. 855 individuals who were HIV negative by self-report participated [mean age: 33.6 (SD 9.2); 45.5% male]. Among all respondents, 14.5% were aware of, and 26.0% would be willing to use PrEP. Among high-risk individuals (N = 327), 19.8% knew about and 35.1% would be willing to use PrEP. The most common reason for lack of willingness among high-risk individuals was low self-perceived risk (65.1%). In multivariate analysis, individuals reporting single marital status [OR 1.8 (1.2, 2.5), p = 0.002], depressive symptoms [OR 1.6 (1.2, 2.2), p = 0.0054], arrest history [OR 1.7(1.2, 2.4), p = 0.0003], PrEP knowledge [OR 1.5 (1.0, 2.3), p = 0.0247] and belief in HIV conspiracies [OR 1.3 (1.1, 1.5), p = 0.0075] were more willing to use PrEP. Participants who saw a health care provider less frequently were less willing to use PrEP [OR 0.5 (0.4, 0.8), p = 0.0044]. Among a nationally representative sample of Black individuals, few high risk individuals were willing to use PrEP. Interventions to increase risk awareness, PrEP knowledge and access to care are necessary to improve PrEP uptake.

ObjectiveTo determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country.MethodsA cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years) and adolescents (10–19 years) attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record.ResultsData from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001). The median age at ART initiation was 8.0 years (IQR 3.0, 12.0); median time on ART was 2.9 years (IQR 1.7, 4.5). On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years) at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001). Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180). Children (<10y) on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239). In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324), and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379) were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates.ConclusionsDuring routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes.

Non-U.S.-born black individuals comprise a significant proportion of the new diagnoses of HIV in the United States. Concurrent diagnosis (obtaining an AIDS diagnosis in close proximity to an initial diagnosis of HIV) is common in this subpopulation. Although efforts have been undertaken to increase HIV testing among African Americans, little is known about testing patterns among non-U.S.-born black people. A cross-sectional survey was self-administered by 1060 black individuals in Massachusetts (57% non-U.S.-born) to assess self-reported rates of HIV testing, risk factors, and potential barriers to testing, including stigma, knowledge, immigration status, and access to health care. Bivariate analysis comparing responses by birthplace and multivariate logistic regression assessing correlates of recent testing were completed. Non-U.S.-born individuals were less likely to report recent testing than U.S.-born (41.9% versus 55.6%, p < 0.0001). Of those who recently tested, the majority did so for immigration purposes, not because of perceived risk. Stigma was significantly higher and knowledge lower among non-U.S.-born individuals. In multivariate analysis, greater length of time since immigration was a significant predictor of nontesting among non-U.S.-born (adjusted odds ratio [AOR] 0.56, 95% confidence interval [CI] 0.36-0.87). Poor health care access and older age were correlated to nontesting in both U.S.-and non-U.S.-born individuals. Our findings indicate that differences in HIV testing patterns exist by nativity. Efforts addressing unique factors limiting testing in non-U.S.-born black individuals are warranted.

Osteoclasts express high levels of vacuolar H(+)-ATPase (V-ATPase) in their ruffled membranes, driving the secretion of H+ required for normal bone resorption. Previous reports have suggested that the B subunit of the osteoclast V-ATPase differs from those expressed in kidney and other tissues. In this study, B subunit isoform-specific antibodies and cDNA probes were used to examine which B subunit isoform is expressed in osteoclasts and osteoclast-like cells. Immunoblotting and RNA hybridization analysis were used to demonstrate that cells from an osteoclast-rich mouse bone marrow culture model express the B2 but not the B1 subunit isoform. Immunocytochemical staining of murine osteoclasts generated in vitro and of native rat osteoclasts in bone sections showed that the B2 but not the B1 isoform was expressed at high levels and was polarized to the ruffled membrane. Human marrow cultures and monocyte-derived macrophages, used as models for osteoclasts, also expressed the B2 but not the B1 subunit isoform. These results indicate that V-ATPases containing the B2 subunit isoform mediate osteoclast bone resorption.

Access to pediatric HIV treatment in resource-limited settings has risen significantly. However, little is known about the quality of care that pediatric or adolescent patients receive. The objective of this study is to explore quality of HIV care and treatment in Nigeria and to determine the association between quality of care, loss-to-follow-up and mortality. A retrospective cohort study was conducted including patients ≤18 years of age who initiated ART between November 2002 and December 2011 at 23 sites across 10 states. 1,516 patients were included. A quality score comprised of 6 process indicators was calculated for each patient. More than half of patients (55.5%) were found to have a high quality score, using the median score as the cut-off. Most patients were screened for tuberculosis at entry into care (81.3%), had adherence measurement and counseling at their last visit (88.7% and 89.7% respectively), and were prescribed co-trimoxazole at some point during enrollment in care (98.8%). Thirty-seven percent received a CD4 count in the six months prior to chart review. Mortality within 90 days of ART initiation was 1.9%. A total of 4.2% of patients died during the period of follow-up (mean: 27 months) with 19.0% lost to follow-up. In multivariate regression analyses, weight for age z-score (Adjusted Hazard Ratio (AHR): 0.90; 95% CI: 0.85, 0.95) and high quality indicator score (compared a low score, AHR: 0.43; 95% CI: 0.26, 0.73) had a protective effect on mortality. Patients with a high quality score were less likely to be lost to follow-up (Adjusted Odds Ratio (AOR): 0.42; 95% CI: 0.32, 0.56), compared to those with low score. These findings indicate that providing high quality care to children and adolescents living with HIV is important to improve outcomes, including lowering loss to follow-up and decreasing mortality in this age group.

Uptake of pre-exposure prophylaxis (PrEP) among Black women living in the US is suboptimal. We sought to determine the association between HIV conspiracy beliefs (HIV-related medical mistrust) and willingness to use PrEP among Black women. We analyzed data from the 2016 National Survey on HIV in the Black Community (NSHBC), a nationally representative crosssectional survey. Among NSHBC participants, 522 were women and 347(66.5%) reported expanded PrEP indications. Only 14.1% were aware that PrEP exists; 30.8% reported willingness to use PrEP. HIV-related medical mistrust was reported by 60.4% of women. In multivariable analysis, controlling for income, education, marital status and health care engagement, belief in conspiracy theories was significantly associated with higher willingness to use PrEP. The conspiracy scale item: "there is a cure for HIV, but the government is withholding it from the poor" was independently associated with PrEP willingness. This finding speaks to the need for an improved understanding of the role of HIV-related medical mistrust among Black women to improve uptake of biomedical HIV prevention. KeywordsHIV and women; women and pre-exposure prophylaxis; mistrust and PrEP; HIV conspiracy theories; HIV-related medical mistrust and PrEP; Black women and PrEP; African-American women and PrEP