Hart, Clyde, Catherine McLean, Tammy Evans-Strickfaden, Heidi Jones, John Karon, Janet McNicholl, and Janneke van de Wijgert. "Detection of cervicovaginal infectious and replicating HIV-1 in the evaluation of Carraguard™ microbicide use in HIV-infected women: A Phase 1 randomized, controlled, crossover study in Chiang Rai, Thailand."

Abstract

BACKGROUND: Techniques for detecting infectious HIV-1 in genital secretions should be explored for use in microbicide trials. Cervicovaginal lavages (CVLs) collected during a 3-month Phase 1, three-treatment (Carraguard^® gel, methylcellulose placebo gel, and no product) crossover study among 60 HIV-infected Thai women were tested for infectious and replicating HIV.

METHODS: The treatment sequence was randomly assigned. Women used gel once daily for 7 days during gel months. During each period, CVLs were collected shortly after menses on day 0 (before gel use, 0a), 15 minutes after first gel application (0b), day 7 (after last gel use) and day 14. Cell-free HIV-1 RNA in CVLs was quantified using the Roche Amplicor Monitor HIV-1 kit (1.5). Cell-free infectious HIV-1 and cellular HIV-1 replication were detected using TZM-bl cell cultures and RNA-PCR for multiply-spliced HIV-1 RNA, respectively. Leukocyte levels in CVLs were estimated using a standard urine dipstick.

RESULTS: At baseline (0a), median peripheral blood CD4+ cell count and CVL viral load among study participants were 296 cells/µL and 2.1 log₁₀ copies/mL, respectively. The proportions of women with infectious HIV-1 and viral replication in CVLs were similar across treatment arms and sampling days; infectious HIV-1 was detected in 7%–36% and viral replication in 17%–43% of the CVLs. In each arm, 8–13 women (14%–22%) had a decrease while only 2–4 women (3%–7%) had an increase in CVL infectious HIV-1 from day 0a to 7. Similarly in each arm, 7–13 women (12%–22%) had a decrease while 5–13 women (9%–22%) had an increase in CVL HIV-1 replication. CVL leukocyte levels across all arms were similar on days 0a and 14 but there was a significant difference across the arms at day 7 (p<0.001).

CONCLUSION: The detection of infectious HIV-1 and HIV-1 replication in CVLs were similar across study days and treatment arms even when CVL leukocyte levels were significantly different. Our findings suggest that assaying the HIV-1 virological parameters of CVLs from infected women enrolled in a microbicide trial is feasible and that the results may be useful when evaluating a product’s safety and its impact on HIV-1 transmissibility.

Poster Session
Monday, 24 April 2006, 12:30–1:30 pm
Tuesday, 25 April 2006, 12:30–1:30 pm

Microbicides 2006

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This page updated 3 April 2006

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