-
[show abstract]
[hide abstract]
ABSTRACT: To assess the pharmacokinetics of dapivirine in plasma and dapivirine concentrations in cervicovaginal fluids (CVF) and cervicovaginal tissues following vaginal administration of dapivirine microbicide gel in healthy, HIV-negative women for 10 days. A randomized, double-blind, phase I study was conducted at a single research center in South Africa. A total of 18 women used dapivirine gel (0.001%, 0.005%, or 0.02%) once daily on Days 1 and 10 and twice daily on Days 2-9. Pharmacokinetics of dapivirine were assessed in plasma on Days 1 and 10. Dapivirine concentrations were measured in CVF on Days 1 and 10 and in cervicovaginal tissues on Day 10. Safety was evaluated through laboratory tests (hematology, clinical chemistry, and urinalysis), physical examinations, and assessment of adverse events. Plasma concentrations of dapivirine increased over time with gel dose and were greater on Day 10 (C(max) 31 to 471 pg/ml) than Day 1 (C(max) 23 to 80 pg/ml). T(max) was 10-12 h on Day 1, and 9 h on Day 10. Concentrations in CVF generally increased with dose but were highly variable among participants. Mean peak values ranged from 4.6-8.3 × 10(6) pg/ml on Day 1 and from 2.3-20.7 × 10(6) pg/ml on Day 10 across dose groups. Dapivirine was detectable in all tissue biopsies on Day 10 at concentrations of 1.0-356 × 10(3) pg/mg. CONCLUSIONS: Dapivirine was widely distributed throughout the lower genital tract with low systemic absorption when administered in a vaginal gel formulation for 10 consecutive days. The gel was safe and well tolerated.
AIDS research and human retroviruses 11/2010; 26(11):1181-90. · 2.18 Impact Factor
-
Annalene M Nel, Paul Coplan,
Janneke H van de Wijgert,
Saidi H Kapiga,
Claire von Mollendorf,
Eveline Geubbels,
Joseph Vyankandondera,
Helen V Rees,
Gileard Masenga,
Ireen Kiwelu,
Jocelyn Moyes,
Shanique C Smythe
[show abstract]
[hide abstract]
ABSTRACT: To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women.
Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine.
Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less.
Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.
AIDS (London, England) 07/2009; 23(12):1531-8. · 4.91 Impact Factor
-
Saidi H Kapiga,
Noel E Sam,
Heejung Bang,
Quanhong Ni,
Trong T H Ao,
Ireen Kiwelu,
Sarah Chiduo,
Uzodinma Ndibe,
George Seage, Paul Coplan,
John Shao,
Zeda F Rosenberg,
Max Essex
[show abstract]
[hide abstract]
ABSTRACT: We examined the role of herpes simplex virus type 2 (HSV-2) and other genital infections on human immunodeficiency virus type 1 (HIV-1) incidence in a cohort study conducted between 2002 and 2005 among female bar/hotel workers in Moshi, Tanzania.
At baseline and every 3 months thereafter, participants were interviewed, and blood and genital samples were collected. Predictors of HIV-1 incidence were evaluated using a Cox proportional hazards regression model.
Of 845 women who were HIV-1 seronegative at baseline, 689 (81.5%) were monitored in the study for a total of 698.6 person-years at risk (PYARs). The overall HIV-1 incidence was 4.6/100 PYARs (95% confidence interval [CI], 3.0-6.2/100 PYARs), and condom use was very low. After adjustment for other risk factors, the risk of HIV-1 was increased among women with HSV-2 at baseline (hazard ratio [HR], 4.3 [95% CI, 1.5-12.4]) and in those who acquired HSV-2 during the study period (HR, 5.5 [95% CI, 1.2-25.4]). Other independent predictors of HIV-1 were baseline chlamydial infection (HR, 5.2), bacterial vaginosis (HR, 2.1), and the occurrence of genital ulcers (HR, 2.7).
HSV-2 and other genital infections were the most important risk factors for HIV-1. Control of these infections could help to reduce HIV-1 incidence in this population.
The Journal of Infectious Diseases 05/2007; 195(9):1260-9. · 6.41 Impact Factor
-
Katherine K Tassiopoulos,
George Seage,
Noel Sam,
Ireen Kiwelu,
John Shao,
Trong T H Ao,
Max Essex, Paul Coplan,
Zeda Rosenberg,
Michael Hughes,
Saidi Kapiga
[show abstract]
[hide abstract]
ABSTRACT: Herpes simplex virus (HSV) type 2 increases the risk of human immunodeficiency virus (HIV) infection, and, in regions with high prevalence of both viruses, control of HSV-2 may be an effective method of HIV prevention. Identification of modifiable factors for prevention of HSV-2 infection is essential. We conducted this study among female bar and hotel workers in Moshi, Tanzania.
Factors associated with prevalent infection were examined among 1039 women. Predictors of incident infection were examined among 360 women initially HSV-2 negative, with at least 1 follow-up visit.
HSV-2 prevalence was 56.3% (95% confidence interval [CI], 53.3%-59.3%). Only 2.5% of women able to name a sexually transmitted infection named herpes. Incidence was 14.2 cases/100 person-years (95% CI, 10.5-18.8 cases/100 person-years). Incident HSV-2 infection was independently associated with HIV infection, younger age of sexual initiation, ethnicity, alcohol consumption, and having a male partner with other sexual partners.
The occurrence of HSV-2 is high in this population, but knowledge is low. Development of education programs to increase awareness of HSV-2 is critical. The control of both HSV-2 and HIV infections is a major public health priority in Moshi. Prevention interventions in this and other high prevalence populations might most effectively target younger women, before initiation of sexual activity.
The Journal of Infectious Diseases 03/2007; 195(4):493-501. · 6.41 Impact Factor
