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Rebecca Dillingham,
Paul Leger,
Carole-Anne Beauharnais,
Erica Miller,
Angela Kashuba,
Steven Jennings,
Kathryn Dupnik,
Amidou Samie,
Etna Eyma,
Richard Guerrant, Jean Pape,
Daniel Fitzgerald
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ABSTRACT: Diarrhea in patients with acquired immunodeficiency syndrome (AIDS) may cause malabsorption of medications and failure of antiretroviral therapy (ART). We prospectively evaluated human immunodeficiency virus-1 (HIV-1)-infected patients with and without chronic diarrhea initiating ART in Haiti. We report mean plasma antiretroviral concentrations at 2 and 4 weeks. We measured plasma HIV-1 RNA levels at four points. Fifty-two HIV-1-infected patients (26 matched pairs) were enrolled. No differences in antiretroviral concentrations were detected. At week 24, 18/25 (72%) cases and 16/24 (68%) controls had undetectable plasma HIV-1 RNA levels (P = 0.69). Patients with plasma HIV-1 RNA levels > 50 copies/mL at week 24 had lower early efavirenz concentrations than patients with undetectable HIV-1 RNA (2,621 ng/mL versus 5,278 ng/mL; P = 0.02). Diarrhea at ART initiation does not influence plasma concentrations of the medications evaluated. Virologic outcome at Week 24 does correlate with efavirenz concentrations early in therapy but not with the presence of chronic diarrhea.
The American journal of tropical medicine and hygiene 06/2011; 84(6):878-82. · 2.59 Impact Factor
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Gavin J Churchyard,
Cecilia Morgan,
Elizabeth Adams,
John Hural,
Barney S Graham,
Zoe Moodie,
Doug Grove,
Glenda Gray,
Linda-Gail Bekker,
M Juliana McElrath, [......],
Artur Kalichman,
J Peter Figueroa, Jean Pape,
Mauro Schechter,
Olivier Defawe,
Stephen C De Rosa,
David C Montefiori,
Gary J Nabel,
Lawrence Corey,
Michael C Keefer
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ABSTRACT: The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean.
480 participants were evenly randomized to receive either: DNA (4 mg i.m. by Biojector) at 0, 1 and 2 months, followed by rAd5 (10(10) PU i.m. by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost.
The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%-94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients.
The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.
ClinicalTrials.gov NCT00125970.
PLoS ONE 01/2011; 6(8):e21225. · 4.09 Impact Factor
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Ouzama Nicholson,
Fay Dicandilo,
James Kublin,
Xiao Sun,
Erin Quirk,
Michelle Miller,
Glenda Gray, Jean Pape,
Michael N Robertson,
Devan V Mehrotra,
Steven Self,
Katherine Turner,
Jorge Sanchez,
Punnee Pitisuttithum,
Ann Duerr,
Sheri Dubey,
Lisa Kierstead,
Danilo Casimiro,
Scott M Hammer
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ABSTRACT: Abstract The safety and immunogenicity of the MRK adenovirus type 5 (Ad5) HIV-1 clade B gag vaccine was assessed in an international Phase I trial. Three-hundred and sixty healthy HIV-uninfected adults were enrolled on five continents. Subjects received placebo or 1 × 10(9) or 1 × 10(10) viral particles (vp) per dose of the MRKAd5 HIV-1 gag vaccine at day 1, week 4, and week 26. Immunogenicity was evaluated using an IFN-γ ELISPOT gag 15-mer assay with positive responses defined as ≥55 SFC/10(6) PBMCs and ≥4-fold over mock control. The vaccine was well tolerated. The most common adverse events were injection site reactions, headache, pyrexia, diarrhea, fatigue, and myalgia. At week 30, geometric mean ELISPOT responses were 24, 114, and 226 SFC/10(6) PBMCs in the placebo, 1 × 10(9) vp/dose, and 1 × 10(10) vp/dose groups, respectively. Overall, responses to 1 × 10(10) vp were 85% and 68% in subjects with low (≤200) and high (>200) baseline Ad5 titers, respectively. The MRKAd5 HIV-1 gag vaccine was immunogenic in diverse geographic regions. Gag ELISPOT responses were greater in the 1 × 10(10) vp/dose groups than in the 1 × 10(9) vp/dose groups. Data from this first international study indicate that adenovirus-vectored vaccines are well tolerated and may be immunogenic in subjects from regions with high prevalence of preexisting Ad5 immunity.
AIDS research and human retroviruses 11/2010; · 2.18 Impact Factor
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ABSTRACT: Many Haitian adolescents and youth are highly vulnerable to HIV infection. It was important to define the risk factors of the young people who are already seeking care.
Among 3391 sexually active 13- to 25-year-olds in our Voluntary Counseling and Testing (VCT) Center in Port-au-Prince from October 2005 to September 2006, we assessed associations between demographic and behavioral factors and HIV status using multivariable logistic regression analyses.
We diagnosed HIV infection in 6.3% of 2533 females and 5.5% of 858 males. Age-specific prevalence was 3.4% for 13- to 15-year-olds, 4.7% for 16-19, and 6.8% for 20-25 (P = 0.02). Poor education, not residing with parents, currently or formerly married, having a child, and being self-referred or referred by others VCT services were significant predictors of HIV in females. HIV infection was associated with considering oneself at higher risk, although most youth did not recognize this risk. HIV in females was also associated with suspected/confirmed sexually transmitted infection, especially genital ulcers (ORadj = 2.28, 95% confidence interval: 1.26 to 4.13), years of sexual activity (Ptrend = 0.07), and suspicion that partners had other partners or an sexually transmitted infection. Among males, HIV was associated with drug use (though uncommon) and sexual debut with a casual/unknown person (ORadj = 3.18, 95% confidence interval: 1.58 to 6.42). HIV-infected young people were more likely to be rapid plasma reagin positive and less likely to use condoms.
Young Haitians are a key target for HIV prevention and care and avail themselves readily of youth-focused VCT services.
JAIDS Journal of Acquired Immune Deficiency Syndromes 10/2009; 52(4):498-508. · 4.43 Impact Factor
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Gaston Djomand,
Barbara Metch,
Carmen D Zorrilla,
Yeycy Donastorg,
Martin Casapia,
Tonya Villafana, Jean Pape,
Peter Figueroa,
Marianne Hansen,
Susan Buchbinder,
Chris Beyrer
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ABSTRACT: Successful recruitment and retention of HIV-uninfected at-risk participants are essential for HIV vaccine efficacy trials. A multicountry vaccine preparedness study was started in 2003 to assess enrollment and retention of HIV-negative high-risk participants and to assess their willingness to participate in future vaccine efficacy trials. HIV-negative high-risk adults were recruited in the Caribbean, in Southern Africa, and in Latin America, and were followed for 1 year. Participants included men who have sex with men, heterosexual men and women, and female sex workers. History of sexually transmitted infections and sexual risk behaviors were recorded with HIV testing at 0, 6, and 12 months, and willingness to participate in future vaccine trials was recorded at 0 and 12 months. Recruitment, retention, and willingness to participate in future trials were excellent at 3 of the 6 sites, with consistent declines in risk behaviors across cohorts over time. Although not powered to measure seroincidence, HIV seroincidence rates per 100 person-years (95% confidence interval [CI]) were as follows: 2.3 (95% CI: 0.3 to 8.2) in Botswana, 0.5 (95% CI: 0 to 2.9) in the Dominican Republic, and 3.1 (95% CI: 1.1 to 6.8) in Peru. The HIV Vaccine Trials Network 903 study helped to develop clinical trial site capacity, with a focus on recruitment and retention of high-risk women in the Americas, and improved network and site expertise about large-scale HIV vaccine efficacy trials.
JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2008; 48(1):82-9. · 4.43 Impact Factor
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ABSTRACT: Abstract
Background
We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART) to patients with AIDS in Haiti.
Methods
We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART.
Results
The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labor $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year. We estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART.
Conclusion
Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers.
Cost Effectiveness and Resource Allocation. 01/2008;
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