Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a phase I randomized clinical trial in healthy Serbian adults.

This study was a phase I double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a Serbian-produced seasonal trivalent split, inactivated influenza vaccine in healthy adults. The vaccine was manufactured in eggs by the Torlak Institute of Virology, Vaccines and Sera, Belgrade, Serbia and contained A/H1N1, A/H3N2 and B viruses. The clinical trial took place at the Clinical Center of Serbia in Belgrade. Sixty healthy volunteers, aged 18-45 years, were enrolled in the trial. On the day of immunization, volunteers were randomly assigned to receive either a single dose of the trivalent seasonal influenza vaccine (15 µg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Subjects were monitored for adverse events through a clinical history and physical examination, and blood was taken for testing at screening and on day 8 to assess vaccine safety. Serum samples obtained before and 21 days after immunization were tested for influenza antibody titers using hemagglutination-inhibition (HAI) and microneutralization (MN) tests. No serious adverse events were reported. Pain and tenderness at the injection site were the most commonly reported symptoms in both vaccine and placebo groups. Overall, serum HAI responses of fourfold or greater magnitude were observed to H1, H3, and B antigen in 80%, 75%, and 70% of subjects, respectively. Seroprotection rates as measured by HAI were also high (100%, 100% and 86.67%, respectively, for H1, H3 and B). Thus, Torlak's seasonal trivalent influenza vaccine was not associated with adverse events, was well-tolerated and immunogenic. It should be further evaluated in clinical trials to provide sufficient safety and immunogenicity data for licensing in Serbia.

HIV Sexual Risk and Syndemics among Women in Three Urban Areas in the United States: Analysis from HVTN 906.

Limited data are available on the longitudinal occurrence of syndemic factors among women at risk for HIV infection in the USA and how these factors relate to sexual risk over time. HVTN 906 was a longitudinal study enrolling 799 HIV-uninfected women in three cities. Assessments were done at baseline, 6, 12, and 18 months to assess syndemic factors (low education, low income, unemployment, lack of health insurance, housing instability, substance use, heavy alcohol use, partner violence, incarceration) and sexual risk outcomes. For each sexual risk outcome, a GEE model was fit with syndemic factors or syndemic score (defined as sum of binary syndemics, ranging from 0 to 9), visit, study site, age and race/ethnicity as predictors to examine the multivariable association between syndemic factors and outcomes over time. Odds of unprotected sex while drunk or high were significantly higher when women reported lack of health insurance, substance and heavy alcohol use and partner violence. Housing instability, substance and heavy alcohol use, partner violence and recent incarceration were associated with higher odds of having multiple sexual partners. Odds of sex exchange were significantly higher in the presence of unemployment, housing instability, low education, lack of health insurance, substance and heavy alcohol use, partner violence and incarceration. Housing instability, substance and heavy alcohol use, and partner violence were significantly associated with higher odds of unprotected anal sex. Odds of having a recent STI were significantly higher when women reported housing instability and partner violence. There were significantly higher odds of the reporting of any risk outcomes during follow-up with higher syndemic score. This study highlights a group of women experiencing multiple poor social and health outcomes who need to be the focus of comprehensive interventions.

Recruitment of Caribbean female commercial sex workers at high risk of HIV infection.

OBJECTIVE: To evaluate novel eligibility criteria and outreach methods to identify and recruit women at high risk of HIV-1 infection in the Caribbean. METHODS: A prospective cohort study was conducted in 2009-2012 among 799 female commercial sex workers in the Dominican Republic, Haiti, and Puerto Rico. Minimum eligibility criteria included exchange of sex for goods, services, or money in the previous 6 months and unprotected vaginal or anal sex with a man during the same period. Sites used local epidemiology to develop more stringent eligibility criteria and recruitment strategies. Participants were asked questions about HIV/AIDS and their level of concern about participating in an HIV vaccine trial. Logistic regression modeling was used to assess predictors of prevalent HIV infection and willingness to participate in a future HIV vaccine study. RESULTS: HIV prevalence at screening was 4.6%. Crack cocaine use [odds ratio (OR) = 4.2, 95% confidence interval (CI) (1.8-9.0)] was associated with and having sex with clients in a hotel or motel [OR = 0.5, CI (0.3-1.0)] was inversely associated with HIV infection. A total of 88.9% of enrolled women were definitely or probably willing to participate in a future HIV vaccine trial. CONCLUSIONS: This study indicated that local eligibility criteria and recruitment methods can be developed to identify and recruit commercial sex workers with higher HIV prevalence than the general population who express willingness to join an HIV vaccine trial.

Recruitment of Caribbean female commercial sex workers at high risk of HIV infection / Captación de mujeres profesionales del sexo con alto riesgo de infección por VIH en el Caribe

OBJECTIVE: To evaluate novel eligibility criteria and outreach methods to identify and recruit women at high risk of HIV-1 infection in the Caribbean. METHODS: A prospective cohort study was conducted in 2009-2012 among 799 female commercial sex workers in the Dominican Republic, Haiti, and Puerto Rico. Minimum eligibility criteria included exchange of sex for goods, services, or money in the previous 6 months and unprotected vaginal or anal sex with a man during the same period. Sites used local epidemiology to develop more stringent eligibility criteria and recruitment strategies. Participants were asked questions about HIV/AIDS and their level of concern about participating in an HIV vaccine trial. Logistic regression modeling was used to assess predictors of prevalent HIV infection and willingness to participate in a future HIV vaccine study. RESULTS: HIV prevalence at screening was 4.6%. Crack cocaine use [odds ratio (OR) = 4.2, 95% confidence interval (CI) (1.8-9.0)] was associated with and having sex with clients in a hotel or motel [OR = 0.5, CI (0.3-1.0)] was inversely associated with HIV infection. A total of 88.9% of enrolled women were definitely or probably willing to participate in a future HIV vaccine trial. CONCLUSIONS: This study indicated that local eligibility criteria and recruitment methods can be developed to identify and recruit commercial sex workers with higher HIV prevalence than the general population who express willingness to join an HIV vaccine trial.

OBJETIVO: Evaluar nuevos criterios de selección y métodos extrainstitucionales encaminados a detectar y captar a las mujeres con alto riesgo de contraer la infección por virus de la inmunodeficiencia humana (VIH) en el Caribe. MÉTODOS: Del 2009 al 2012, se llevó a cabo un estudio prospectivo de cohortes de 799 mujeres profesionales del sexo en la República Dominicana, Haití y Puerto Rico. Los requisitos mínimos de selección fueron el intercambio de relaciones sexuales por bienes, servicios o dinero en los últimos 6 meses y las relaciones sexuales vaginales o anales sin protección con un hombre durante el mismo período. En cada centro se aplicaron criterios de selección y estrategias de captación más restrictivos, en función de las características epidemiológicas locales. Se formularon a las participantes preguntas acerca de la infección por el VIH/sida y su motivación para participar en un estudio clínico sobre la vacuna contra el VIH. Se usó un modelo de regresión logística con el fin de analizar los factores pronósticos de prevalencia de infección por el VIH y la voluntad de participar en un estudio futuro sobre la vacuna contra el virus. RESULTADOS: La prevalencia de infección por el VIH en el momento del tamizaje fue 4,6%. El consumo de crack se asoció con la infección por el VIH (razón de posibilidades [OR]: 4,2; intervalo de confianza [IC] de 95%: 1,8-9,0) y la práctica de relaciones sexuales con clientes en un hotel o un motel se asoció inversamente con esta infección (OR: 0,5; IC 95%: 0,3-1,0). El 88,9% de las mujeres inscritas manifestó una disposición decidida o probable de participar en un estudio futuro sobre la vacuna contra el VIH. CONCLUSIONES: Los resultados del estudio indican que es posible formular criterios de selección e introducir métodos de captación locales con el propósito de detectar y captar a las mujeres profesionales del sexo, que presentan una prevalencia de infección por el VIH mayor que la población general y manifiestan una buena disposición de participar en un ensayo clínico sobre la vacuna contra el VIH.

Intentions to use preexposure prophylaxis among current phase 2B preventive HIV-1 vaccine efficacy trial participants.

In November 2010, the iPrEx study reported that preexposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine reduced HIV infections by 44% among men who have sex with men and subsequent trials corroborated efficacy among heterosexual men and women. During regularly scheduled follow-up visits from January to March 2011, participants in an ongoing phase 2b vaccine efficacy trial completed an anonymous Web survey about PrEP. Among 376 respondents, 17% reported they were very likely to use PrEP in the next year. Nonwhite participants were more likely to use PrEP. Among those with some level of interest, intent to use PrEP was greatest if the drug were available through the clinical trial or health insurance. Most (91%) believed taking PrEP would not change their willingness to stay in the vaccine trial and few thought it would affect recruitment. As key stakeholders, currently enrolled trial participants can offer vital input about emerging prevention technologies that may affect the design of future HIV vaccine and nonvaccine prevention trials.

Feasibility of identifying a cohort of US women at high risk for HIV infection for HIV vaccine efficacy trials: longitudinal results of HVTN 906.

BACKGROUND: Identifying cohorts of US women with HIV infection rates sufficient for inclusion in vaccine efficacy trials has been challenging. Using geography and sexual network characteristics to inform recruitment strategies, HVTN 906 determined the feasibility of recruiting a cohort of women at high risk for HIV acquisition. METHODS: HIV uninfected women who reported unprotected sex in the prior 6 months, resided or engaged in risk behavior in local geographical high-risk pockets and/or had a male partner who had been incarcerated, injected drugs, or had concurrent partners were eligible. Behavioral risk assessment, HIV counseling and testing, and pregnancy testing were done at baseline, 6, 12, and 18 months. RESULTS: Among 799 women, 71% were from local high-risk pockets and had high-risk male partners. Median age was 37 years; 79% were Black; and 15% Latina. Over half (55%) reported a new partner in the prior 6 months, 57% reported a male partner who had concurrent female sexual partners, and 37% reported a male partner who had been incarcerated. Retention at 18 months was 79.5%. Annual pregnancy incidence was 12%. Annual HIV incidence was 0.31% (95% confidence interval: 0.06% to 0.91%). Risk behaviors decreased between screening and 6 months with smaller changes thereafter. DISCUSSION: This cohort of women recruited using new strategies based on geography and sexual network characteristics did not have an HIV incidence high enough for HIV vaccine efficacy trials, despite high baseline levels of risk and a high pregnancy rate. New strategies to identify cohorts of US women for efficacy trials are needed.

Recruitment of urban US women at risk for HIV infection and willingness to participate in future HIV vaccine trials.

Enrollment of US women with sufficient risk of HIV infection into HIV vaccine efficacy trials has proved challenging. A cohort of 799 HIV-negative women, aged 18-45, recruited from three US cities was enrolled to assess recruitment strategies based on geographic risk pockets, social and sexual networks and occurrence of sexual concurrency and to assess HIV seroincidence during follow-up (to be reported later). Among enrolled women, 90 % lived or engaged in risk behaviors within a local risk pocket, 64 % had a male partner who had concurrent partners and 50 % had a male partner who had been recently incarcerated. Nearly half (46 %) were recruited through peer referral. At enrollment, 86 % of women said they were willing to participate in a vaccine efficacy trial. Results indicate that participant and partner risk behaviors combined with a peer referral recruitment strategy may best identify an at-risk cohort willing to participate in future trials.

Veterans Aging Cohort Study (VACS): Overview and description.

BACKGROUND: The Veterans Aging Cohort Study (VACS) is a study of human immunodeficiency virus (HIV) infected and uninfected patients seen in infectious disease and general medical clinics. VACS includes the earlier 3 and 5 site studies (VACS 3 and VACS 5) as well as the ongoing 8 site study. OBJECTIVES: We sought to provide background and context for analyses based upon VACS data, including study design and rationale as well as its basic protocol and the baseline characteristics of the enrolled sample. RESEARCH DESIGN: We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection. MEASURES: Data were derived from patient and provider self report, telephone interviews, blood and DNA samples, focus groups, and full access to the national VA "paperless" electronic medical record system. RESULTS: More than 7200 veterans have been enrolled in at least one of the studies. The 8 site study (VACS) has enrolled 2979 HIV-infected and 3019 HIV-uninfected age-race-site matched comparators and has achieved stratified enrollment targets for race/ethnicity and age and 99% of its total target enrollment as of October 30, 2005. Participants in VACS are similar to other veterans receiving care within the VA. VACS participants are older and more predominantly black than those reported by the Centers for Disease Control. CONCLUSIONS: VACS has assembled a rich, in-depth, and representative sample of veterans in care with and without HIV infection to conduct longitudinal analyses of questions concerning the association between alcohol use and related comorbid and AIDS-defining conditions.

The Veterans Aging Cohort Study: observational studies of alcohol use, abuse, and outcomes among human immunodeficiency virus-infected veterans.

This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers/chairs were Joseph Conigliaro and Amy Justice. The presentations were (1) Introduction, by Joseph Conigliaro and Tamra Madenwald; (2) Alcohol and HIV/AIDS: the importance of integrative and translational research, by Kendall Bryant; (3) Alcohol use and abuse among patients with HIV infection, by Joseph Conigliaro and Stephan Maisto; (4) Severity of comorbid alcohol use/abuse in HIV infection, by Amy Justice and Jeffrey Samet; (5) Estimating the impact of alcohol use on long-term HIV outcomes, by Scott Braithwaite and Amy Justice; (6) Homelessness, drug & alcohol use among HIV+ veterans, by Adam Gordon and Robert Cook; and (7) Hepatitis C & alcohol in the VACS 3 study, by Shawn Fultz and Kevin Kraemer. The symposium concluded with a discussion led and facilitated by Diedra Roach.

Psychiatric and neurocognitive disorders among HIV-positive and negative veterans in care: Veterans Aging Cohort Five-Site Study.

BACKGROUND: The risk for psychiatric and neurocognitive disorders among middle-aged and older individuals with HIV infection has not been well characterized. METHODS: The Veterans Aging Cohort 5-Site Study enrolled 1803 patients (1047 HIV-positive) from VA infectious disease and general medicine clinics from September 2001 to June 2002. A convenience subset of 10 patients from each site (n = 50) was consented for formal neurocognitive and psychiatric (NCP) testing. Data from this subset were linked to the larger sample. RESULTS: Kappa scores for agreement beyond chance were fair for available measures when compared with formal NCP testing. Using available measures, depressive symptoms (PHQ-9 and provider reported), alcohol abuse or dependence (ICD-9 codes), and drug abuse or dependence (DAST-10) decreased with age in HIV-negative subjects (P trend <0.05) but did not among HIV-positive subjects (P > 0.05). HIV-positive subjects demonstrated higher prevalence of these conditions with increasing age when compared to HIV-negative subjects. Patient report of memory problems increased with age among both groups after excluding those reporting symptoms of depression (PHQ-9e > or = 10). CONCLUSION: Available measures were no substitute for formal NCP testing. Older HIV-positive veterans demonstrate greater prevalence of depressive symptoms, alcohol abuse or dependence, and drug abuse or dependence than age-matched, HIV-negative veterans. Both groups reported increased memory problems with advancing age. This preliminary work suggests a substantial prevalence of psychiatric and neurocognitive problems among middle-aged and older HIV-infected individuals.