Tobacco Use and Sustained Viral Suppression in Youth Living with HIV.

Tobacco has been associated with worse HIV disease progression in adult samples of people living with HIV; however, studies have yet to examine these effects in youth living with HIV (YLWH). This study examined the association between tobacco smoking behaviors and sustained viral suppression among a sample of 820 YLWH who were recruited through the Adolescent Medicine Trials Network for HIV Interventions. Participants completed a cross-sectional survey and then staff abstracted viral suppression data from medical records for up to 26 weeks prior to enrollment. Overall, 20.4% of youth reported daily or almost daily tobacco use. In multivariable analyses, older age and daily or almost daily tobacco smoking, and ART adherence remained statistically significant in predicting sustained viral suppression over the study period. These findings underscore the need for tobacco screening and interventions in HIV care settings in order to identify youth in need of additional smoking cessation services.

A cross-sectional study examining associations between substance use frequency, problematic use and STIs among youth living with HIV.

OBJECTIVES: This study sought to examine the prevalence of STIs and whether substance use frequency and/or problematic use-specifically alcohol, marijuana and other drugs-was associated with having an STI diagnosis among youth living with HIV (YLWH) METHODS: A sample of 823 YLWH were recruited at 14 adolescent HIV clinics through the Adolescent Medicine Trials Network for HIV Interventions. Study staff abstracted STI data from medical records for up to 26 weeks prior to participants' completing a cross-sectional survey including the ASSIST (Alcohol, Smoking and Substance Involvement Screening Test), which measures substance use frequency and consequences. RESULTS: Almost one-third of youth had been diagnosed with an STI (30.5%) at the time of their baseline assessment. In multivariable analyses, those who engaged in weekly or greater marijuana use (adjusted OR (AOR)=10.66, 95% CI: 4.39 to 25.87, P<0.001) had an increased odds of being diagnosed with an STI. Additionally, youth who met alcohol use criteria for moderate (AOR=5.23, 95% CI: 2.50 to 10.93, P<0.001) and high risk (AOR=6.53, 95% CI: 1.20 to 35.68, P<0.05) alcohol use had an increased odds of being diagnosed with an STI compared with low-risk alcohol users. CONCLUSIONS: Study findings underscore the need to investigate the role of greater frequency of marijuana use and problematic alcohol use in STI incidence among YLWH. Given the associations between both substance use frequency and problematic use in STI diagnoses among YLWH seen in HIV care settings, clinicians should use validated substance use screening tools which capture both frequencies and consequences in order to identify YLWH who may need further evaluation and treatment.

Stem-loop binding protein is a multifaceted cellular regulator of HIV-1 replication.

A rare subset of HIV-1-infected individuals is able to maintain plasma viral load (VL) at low levels without antiretroviral treatment. Identifying the mechanisms underlying this atypical response to infection may lead to therapeutic advances for treating HIV-1. Here, we developed a proteomic analysis to compare peripheral blood cell proteomes in 20 HIV-1-infected individuals who maintained either high or low VL with the aim of identifying host factors that impact HIV-1 replication. We determined that the levels of multiple histone proteins were markedly decreased in cohorts of individuals with high VL. This reduction was correlated with lower levels of stem-loop binding protein (SLBP), which is known to control histone metabolism. Depletion of cellular SLBP increased promoter engagement with the chromatin structures of the host gene high mobility group protein A1 (HMGA1) and viral long terminal repeat (LTR), which led to higher levels of HIV-1 genomic integration and proviral transcription. Further, we determined that TNF-α regulates expression of SLBP and observed that plasma TNF-α levels in HIV-1-infected individuals correlated directly with VL levels and inversely with cellular SLBP levels. Our findings identify SLBP as a potentially important cellular regulator of HIV-1, thereby establishing a link between histone metabolism, inflammation, and HIV-1 infection.

Bundling Human Papillomavirus Vaccination and Rapid Human Immunodeficiency Virus Testing for Young Gay and Bisexual Men.

This study explored the feasibility and acceptability of a bundled human papillomavirus (HPV) vaccine and human immunodeficiency virus (HIV) testing program for young gay and bisexual men (YGBM). YGBM aged 18-26 years (N=55) were recruited to receive HPV vaccine with optional HIV testing and personalized counseling. Sexual risk behaviors and knowledge were assessed at three study visits. By visit 3, about 98% had received an HIV test with HPV vaccination; 59% received repeat HIV testing. Findings support the bundling of HPV vaccination with HIV testing among YGBM. Future directions include examining the scalability of integrating clinic-based HIV and HPV healthcare services.

HPV vaccination practices among juvenile justice facilities in the United States.

The juvenile justice setting provides a unique opportunity to administer the human papillomavirus (HPV) vaccine to a high-risk, medically underserved population. We examined current HPV vaccination practices in the United States. Most states (39) offer the HPV vaccine to females committed to juvenile justice facilities.

Safety and immunogenicity of adenovirus-vectored near-consensus HIV type 1 clade B gag vaccines in healthy adults.

Vaccines inducing pathogen-specific cell-mediated immunity are being developed using attenuated adenoviral (Ad) vectors. We report the results of two independent Phase I trials of similar replication-deficient Ad5 vaccines containing a near-consensus HIV-1 clade B gag transgene. Healthy HIV-uninfected adults were enrolled in two separate, multicenter, dose-escalating, blinded, placebo-controlled studies to assess the safety and immunogenicity of a three-dose homologous regimen of Ad5 and MRKAd5 HIV-1 gag vaccines given on day 1, week 4, and week 26. Adverse events were collected for 29 days following each intradeltoid injection. The primary immunogenicity endpoint was the proportion of subjects with a positive unfractionated Gag-specific IFN-gamma ELISPOT response measured 4 weeks after the last dose (week 30). Analyses were performed after combining data for each dose group from both protocols, stratifying by baseline Ad5 titers. Overall, 252 subjects were randomized to receive either vaccine or placebo, including 229 subjects (91%) who completed the study through week 30. Tolerability and immunogenicity did not appear to differ between the Ad5 and MRKAd5 vaccines. The frequency of injection-site reactions was dose dependent. Systemic adverse events were also dose dependent and more frequent in subjects with baseline Ad5 titers <200 versus > or =200, especially after the first dose. The percent of ELISPOT responders and the ELISPOT geometric means overall were significantly higher for all four vaccine doses studied compared to placebo, and were generally higher in vaccine recipients with baseline Ad5 titers <200 versus > or = 200. Ad5 titers increased after vaccination in a dose-dependent fashion. Both Ad5-vectored HIV-1 vaccines were generally well tolerated and induced cell-mediated immune responses against HIV Gag-peptides in the majority of healthy adults with baseline Ad5 titers <200. Preexistent and/or vaccine-induced immunity to the Ad5 vector may dampen the CMI response to HIV Gag.

HIV seroconversion without infection after receipt of adenovirus-vectored HIV type 1 vaccine.

BACKGROUND: We analyzed human immunodeficiency virus (HIV) seroresponses from 3 phase I HIV-1 vaccine trials to assess the frequency of vaccine-induced seroconversion. METHODS: HIV-1 and HIV-2 enzyme-linked immunosorbent assay (ELISA) was performed during trials of adenovirus type 5 (Ad5)-vectored clade B HIV-1 monovalent gag and trivalent gag/pol/nef vaccines given to HIV-seronegative adults. Doses were administered at day 1, week 4, and week 26. Results were analyzed by vaccine formulation and dose and were stratified by baseline Ad5 titer. ELISA-positive samples were reflexively tested by Western blotting. RESULTS: Overall, 165 (41%) of 406 evaluable vaccine recipients had positive ELISA results but negative PCR results by week 78. Seroconversion rates were directly related to vaccine dose, were inversely related to baseline Ad5 titer, and were unaffected by vaccine valency. One hundred (89%) of 113 evaluable patients with low baseline Ad5 antibody titers (or=1 dose of vaccine with >or=1 x 10(10) gag-containing Ad5 particles per dose experienced seroconversion. Of 163 vaccine recipients who had positive ELISA results and available Western blot results, 150 (92%) had indeterminate results of Western blot, typically involving bands at p24, p40, and/or p55. Thirteen uninfected patients (8%) had equivocally positive Western blot results, usually because of an additional weak glycoprotein 41 band. Env-specific enzyme immunoassay results were falsely positive for 2 uninfected vaccine recipients. CONCLUSIONS: Positive ELISA results were similarly common for monovalent and trivalent vaccine recipients. Vaccine dose and baseline Ad5 immunity were major determinants of vaccine-induced seroconversion rates. Corresponding Western blots characteristically showed bands directed only at Gag proteins, which helped to distinguish HIV-uninfected vaccine recipients who experienced seroconversion from true HIV-infected patients. If available, an enzyme immunoassay exclusively targeting proteins not expressed by the vaccine should be the screening test of first choice for vaccine recipients.

A review of the case for hepatitis B vaccination of high-risk adults.

The sequelae of hepatitis B virus infection include fulminant liver failure, chronic liver disease, hepatocellular carcinoma, and death. The hepatitis B vaccine is efficacious, safe, and cost-effective, but has been consistently underutilized in high-risk adults despite long-standing recommendations. Instituting routine hepatitis B vaccination for high-risk adults in settings such as prisons and jails, sexually transmitted disease clinics, drug treatment centers, and needle exchange programs could prevent up to 800 cases of hepatitis, and 10 deaths from hepatitis, per 10,000 vaccinations, with an overall cost savings. Low rates of completion of the three-dose series and lack of funding for adult immunizations have always been challenges to offering hepatitis B vaccines to high-risk adults. However, there is benefit to an incomplete vaccination series, and high-risk populations are accessible for follow-up vaccination outside of traditional medical settings. A clear national objective and federal funding for vaccinating high-risk adults are needed.

Acceptability of sexually transmitted infection screening among women in short-term substance abuse treatment.

BACKGROUND: Substance abuse treatment centers provide an opportunity to offer sexually transmitted infection (STI) screening to a high-risk and hard-to-reach population. GOAL: The goal was to assess STI prevalence, risk factors, and acceptability of STI screening among females at substance abuse treatment centers with use of urine testing by ligase chain reaction and self-collected swab specimens. STUDY DESIGN: Adult, female inpatients were offered free testing and treatment for chlamydia infection, gonorrhea, and trichomonas infection. Interviews were conducted to collect risk behavior data. RESULTS: Eighty-six percent of inpatients (180/209) accepted testing. Twenty-three percent (41/177) had an STI. Of those with an STI, 90% (37/41) had trichomonas infection. All 41 infected patients received treatment. Drug use before sex, exchange of sex for money/drugs, and any gynecological complaint were significantly associated with infection. Most women were uninsured (76%). Only 45% had undergone a medical examination in the past year. CONCLUSION: STI screening is highly acceptable among women in substance abuse treatment centers. Substance users are at high risk for STIs and may not otherwise receive medical care.