Statistical Center for Research and Prevention

Seattle, WA, United States

Statistical Center for Research and Prevention

Seattle, WA, United States
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Bigham A.W.,University of Michigan | Bruyn G.D.,University of Witwatersrand | Ronald A.,University of Manitoba | Mugo N.R.,University of Nairobi | And 3 more authors.
Journal of Infectious Diseases | Year: 2014

Objective. We evaluated Toll-like receptors (TLRs) single nucleotide polymorphisms (SNPs) for associations with HIV-1 acquisition, set-point and disease progression in African couples. Methods. Seven candidate and 116 haplotype-tagging SNPs (tagSNPs) were genotyped in 504 HIV-1 infected cases, and 343 seronegative controls. Results. TLR9 1635A/G was associated with reduced HIV-1 acquisition among HIV-seronegative controls with high but not low HIV-1 exposure (odds ratio [OR] = 0.7; P = .03 and OR = 0.9, P = .5, respectively). TLR7 rs179012 and TLR2 597C/T reduced set-point; the latter modified by time since HIV-1 acquisition. TLR8 1A/G reduced disease progression. Conclusions. TLR SNPs impact HIV-1 outcomes with epidemiologic factors modifying these relationships. © 2013 The Author.

Philip S.S.,University of California at San Francisco | Yu X.,Statistical Center for Research and Prevention | Donnell D.,Statistical Center for Research and Prevention | Vittinghoff E.,University of California at San Francisco | Buchbinder S.,University of California at San Francisco
PLoS ONE | Year: 2010

Background: Seroadaptation strategies such as serosorting and seropositioning originated within communities of men who have sex with men (MSM), but there are limited data about their effectiveness in preventing HIV transmission when utilized by HIV-negative men. Methodology/Principal Findings: Data from the EXPLORE cohort of HIV-negative MSM who reported both seroconcordant and serodiscordant partners were used to evaluate serosorting and seropositioning. The association of serosorting and seropositioning with HIV seroconversion was evaluated in this cohort of high risk MSM from six U.S. cities. Serosorting was independently associated with a small decrease in risk of HIV seroconversion (OR=0.88; 95%CI, 0.81-0.95), even among participants reporting $10 partners. Those who more consistently practiced serosorting were more likely to be white (p= 0.01), have completed college (p=,0.0002) and to have had 10 or more partners in the six months before the baseline visit (p=0.01) but did not differ in age, reporting HIV-infected partners, or drug use. There was no evidence of a seroconversion effect with seropositioning (OR 1.02, 95%CI, 0.92-1.14). Significance: In high risk HIV uninfected MSM who report unprotected anal intercourse with both seroconcordant and serodiscordant partners, serosorting was associated with a modest decreased risk of HIV infection. To maximize any potential benefit, it will be important to increase accurate knowledge of HIV status, through increased testing frequency, improved test technology, and continued development of strategies to increase disclosure. © 2010 Philip et al.

Barresi P.,University of California at San Francisco | Husnik M.,Statistical Center for Research and Prevention | Camacho M.,New York Blood Center | Powell B.,Howard Brown Health Center | And 4 more authors.
AIDS Education and Prevention | Year: 2010

Testing HIV prevention strategies requires that researchers recruit participants at high risk of HIV infection. Data from the EXPLORE Study, a behavioral intervention trial involving men who have sex with men (MSM), were used to examine the relationship between recruitment strategies and participant characteristics, sexual risk behaviors and HIV incidence. The EXPLORE Study used a wide variety of recruitment strategies; no one strategy accounted for more than 20% of enrolled men. Younger men and men of color were more likely to be recruited through club and bar outreach, friend referral, and street outreach. Men reporting 10 or more sexual partners were more likely to be recruited through advertising and street outreach. Men reporting unprotected sex were more likely to be recruited through clinic referrals. HIV incidence did not significantly differ by recruitment strategy. Our findings support the need for a wide range of recruitment strategies in attracting MSM at high risk for HIV into clinical studies. © 2010 The Guilford Press.

PubMed | Magee Womens Hospital of UPMC, Rti International, Johns Hopkins University, Health-U and 6 more.
Type: Journal Article | Journal: Journal of the International AIDS Society | Year: 2016

Vaginal tenofovir (TFV) 1% gel may reduce incident HIV-1 and herpes simplex virus 2 infection. Pregnancy may increase risk of HIV acquisition, and incident HIV in pregnancy potentiates perinatal HIV transmission. Our objective was to investigate the safety and pharmacokinetics of seven days of TFV 1% vaginal gel in term and near-term pregnancy.Ninety-eight healthy pregnant women, stratified to a term cohort followed by a near-term cohort, were enrolled into a 2:1 randomized, double-blinded, placebo-controlled trial. Women received TFV or placebo gel for seven consecutive days with pharmacokinetic sampling on days 0 and 6. Maternal and cord blood were collected at delivery. Primary end points included laboratory and genital adverse events, adverse pregnancy and neonatal outcomes, and maternal TFV levels.Most adverse events were grade 1 and none of the grade 3 or 4 adverse events were related to study product. There was no significant difference in safety end points between the two pregnancy cohorts (Daily TFV 1% vaginal gel use in term and near-term pregnancy appears to be safe and produces low serum drug levels.

Gill D.K.,Imperial College London | Huang Y.,Statistical Center for Research and Prevention | Levine G.L.,U.S. National Institutes of Health | Sambor A.,U.S. National Institutes of Health | And 20 more authors.
PLoS ONE | Year: 2010

Background: The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC-VIMC) was created to provide standardized immunogenicity monitoring services for HIV vaccine trials. The ex vivo interferon-gamma (IFN-γ) ELISpot is used extensively as a primary immunogenicity assay to assess T cell-based vaccine candidates in trials for infectious diseases and cancer. Two independent, GCLP-accredited central laboratories of CTC-VIMC routinely use their own standard operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine trials. Studies are imperatively needed to assess the comparability of ELISpot measurements across laboratories to benefit optimal advancement of vaccine candidates. Methods: We describe an equivalence study of the two independently qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent analysis were managed by independent statisticians to avoid subjectivity. The equivalence of both response rates and positivity calls to a given stimulus was assessed based on pre-specified acceptance criteria derived from a separate pilot study. Findings: Detection of positive responses was found to be equivalent between both laboratories. The 95% C.I. on the difference in response rates, for CMV (21.5%, 1.5%) and CEF (20.4%, 7.8%) responses, were both contained in the prespecified equivalence margin of interval [215%, 15%]. The lower bound of the 95% C.I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC central laboratory already using one of the two SOPs also showed comparability when tested in a smaller sub-study. Interpretation: The described study procedure provides a prototypical example for the comparison of bioanalytical methods in HIV vaccine and other disease fields. This study also provides valuable and unprecedented information for future vaccine candidate evaluations on the comparison and pooling of ELISpot results generated by the CTC-VIMC central core laboratories.

Cranston R.D.,University of Pittsburgh | Hoesley C.,University of Alabama at Birmingham | Carballo-Dieguez A.,Center for Clinical and Behavioral Studies | Hendrix C.W.,Johns Hopkins University | And 5 more authors.
AIDS Research and Human Retroviruses | Year: 2014

Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be "very likely" to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants (p=0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug. © Mary Ann Liebert, Inc.

Kaufman D.R.,Beth Israel Deaconess Medical Center | Li F.,Statistical Center for Research and Prevention | Cruz A.N.,Beth Israel Deaconess Medical Center | Self S.G.,Statistical Center for Research and Prevention | And 2 more authors.
Vaccine | Year: 2012

The global sequence diversity of HIV-1 presents a daunting challenge for vaccine development. We investigated whether a heterologous insert prime-boost regimen could expand global coverage by selectively boosting cellular immune responses to conserved epitopes. Rhesus monkeys were primed and boosted with recombinant adenovirus vectors expressing homologous or heterologous HIV-1 Gag sequences that were optimized to focus responses on highly conserved epitopes. We observed comparable responses directed to specific regions of the Gag protein in all experimental groups without evidence of improved coverage or expanded breadth in the heterologous insert group. These data suggest that antigen-independent factors contribute to the immunodominance patterns of vaccine-elicited cellular immune responses. © 2011 Elsevier Ltd.

Safren S.A.,Massachusetts General Hospital | Safren S.A.,Harvard University | Safren S.A.,Fenway Health | Mayer K.H.,Harvard University | And 11 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015

Background: Combination antiretroviral therapy (ART) for HIV-1-infected individuals prevents sexual transmission if viral load is suppressed. Methods: Participants were HIV-1-infected partners randomized to early ART (CD4 350-550) in HPTN052 (n 886, median follow-up 2.1 years), a clinical trial of early ART to prevent sexual transmission of HIV-1 in serodiscordant couples at 13 sites in 9 countries. Adherence was assessed through pill count (dichotomized at <95%) and through self-report items. Predictors of adherence were mental health and general health perceptions, substance use, binge drinking, social support, sexual behaviors, and demographics. Viral suppression was defined as HIV plasma viral load <400 copies per milliliter. Adherence counseling and couples' counseling about safer sex were provided. Logistic and linear regression models using generalized estimating equation for repeated measurements were used. Findings: Through pill count, 82% of participants were adherent at 1 month and 83.3% at 1 year. Mental health was the only psychosocial variable associated with adherence [pill count, odds ratios (OR) 1.05, 95% confidence intervals (CIs): 1.00 to 1.11; self-report parameter estimate, OR 0.02, 95% CI: 0.01 to 0.04], although regional differences emerged. Pill count (OR 1.19, 95% CI: 1.10 to 1.30) and self-report (OR 1.42, 95% CI: 1.14 to 1.77) adherence were associated with viral suppression. Interpretation: Although adherence was high among individuals in stable relationships taking ART for prevention, mental health and adherence covaried. Assessing and intervening on mental health in the context of promoting adherence to ART as prevention should be explored. Adherence and couples' counseling, feedback about viral suppression, and/or altruism may also help explain the magnitude of adherence observed. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Quan V.M.,Johns Hopkins University | Aramrattana A.,Chiang Mai University | Vongchak T.,Chiang Mai University | Latkin C.,Johns Hopkins University | And 4 more authors.
Journal of Addiction Medicine | Year: 2010

Objectives: To measure mortality rates and assess predictors of all-cause mortality in a cohort of Thai injection drug users (IDUs) who were enrolled and followed up from 2004 through 2006. Methods: In this prospective cohort study, we enrolled 314 community-dwelling IDUs (95% being men; 42% of ethnic minority; median age, 29 years [range, 18-69 years]) and followed up them at 6-month intervals. Mortality rates were calculated based on personyears of follow-up. Marginal Cox proportional hazards models for clustered data were constructed to determine the factors associated with all-cause mortality. Findings: During 445.7 person-years of follow-up, 17 of 314 (5.4%) IDUs died. The all-cause mortality rate was 3.8 per 100 person-years (95% confidence interval [CI] = 2.2-6.1). The standardized mortality ratio was 5.8 (95% CI = 3.5-9.1). The mortality rate among HIV-positive IDUs was 13.4 per 100 person-years (95% CI = 5.4 -27.6). In a marginal Cox proportional-hazards model for clustered data, the excess mortality was associated with HIV-positivity (hazard ratio [HR] = 7.0, 95% CI = 2.8 -17.6), benzodiazepine use (HR = 3.1, 95% CI = 1.1-9.4), and excessive alcohol consumption at enrollment (HR = 3.5, 95% CI = 1.3-9.1). Conclusions: The all-cause mortality among the drug injectors is high. The increased mortality was associated with HIV infection, benzodiazepine use, and excessive alcohol consumption. © 2010 American Society of Addiction Medicine.

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