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Tuesday, March 6, 2012

No sign of tenofovir-induced resistance when PrEP with vaginal gel fails

PRN Report from 19th CROI:

The CAPRISA 004 study has already shown that vaginally applied tenofovir (TFV) gel is a promising HIV prevention modality to protect women from HIV-1 sexual transmission, but the potential emergence of tenofovir resistance remains a concern in women who acquired HIV during the trial despite the lack of evidence of K65R and K70E in plasma virus, as assessed by population sequencing and sensitive testing.

Today, Jeffrey Johnson, from the CDC, spoke about the additional effort to look for TFV resistant HIV-1 in the genital compartments of these subjects where the topically applied drug remains concentrated. Stored, frozen cervicovaginal swabs (BD ProbeTec) collected from 33 women who became infected while assigned to 1% TFV gel in the CAPRISA 004 trial were screened for K65R and K70E resistance mutations using sensitive PCR assays validated for subtype C HIV-1. Estimated duration of infection at the time of swab collection ranged from 3 to 156 days (median = 19 days). Virus shedding, as measured from 10 mL cervicovaginal lavage (CVL), ranged from <70 to 55,000 copies/mL. CVL viral loads and vaginal aspirate TFV levels were available for 14 and 7 women, respectively.

Dr Johnson reported that HIV-1 was often detected in the vaginal compartment, even when high levels of TFV were present, but no definitive evidence of TFV-induced, drug-resistant HIV-1 was found in the genital tract of women with TFV gel breakthrough infections. Together with the absence of resistance mutations in blood, these data suggest that vaginally applied TFV gel poses little risk for selection of TFV resistance and forward transmission of TFV-resistant HIV-1 in a setting where gel users are regularly monitored for HIV seroconversion.

Wei X, Morris L, Naranbhai V, Sibeko S, Abdool Karim Q, Kashuba A, Passmore J-A, Hunt G, Heneine W, Johnson J. Sensitive Tenofovir Resistance Screening of HIV-1 from the Genital Tract of Women with Breakthrough Infections: CAPRISA 004 Tenofovir Gel Trial. Presented March 6, 2012 at the 19th CROI, Seattle, WA. Oral Abstract #33.

Source: Reporting from Seattle for PRN News: James Braun, DO