Adherence key to reducing genital HIV levels in women

Sub-optimal adherence to antiretroviral therapy is the single most important factor associated with genital shedding of HIV in women, investigators report in the online edition of the Journal of Infectious Diseases.

‘This is the largest prospective study of female genital HIV-1 shedding after ART [antiretroviral therapy] initiation that has been conducted to date”, comment the investigators, “adherence was the most important determinant of genital shedding during the women’s first 6 months of NNRTI-based ART and remained a significant predictor after adjustment for plasma viral load.”

Antiretroviral therapy lowers viral load in the blood and other bodily fluids, including genital secretions. Lower genital levels of HIV have been associated with a reduced risk of sexual transmission of the virus and there is currently significant interest in the use of antiretroviral treatment as a method of HIV prevention.

However, it is known that women taking HIV treatment may occasionally shed HIV in their genital fluids.

An international team of investigators wanted to see which factors were associated with this.In particular they wanted to find out whether factors associated with viral shedding in women not receiving treatment - such as infections - remained the most important predictors of viral shedding in women receiving antiretroviral treatment.

They therefore designed a study involving 102 Kenyan women starting antiretroviral therapy. Every three months, viral load was monitored in blood, cervical fluids, and vaginal secretions.

On entry to the study, the women had a median age of 36 years and their median CD4 cell was 122 cells/mm³. All the women were initially prescribed a fixed-dose antiretroviral regimen comprising 3TC/d4T/nevirapine. A total of 95 women completed the six month study.

Adherence was assessed by pill count or patient recall, and at the end of the study, the median adherence level was 99%. The women’s median CD4 cell count had increased to 231 cells/mm³.

At baseline, all the women had detectable HIV in their blood. This fell to 60% after three months of treatment, and 27% at the end of the study.

Virus was detectable in the cervical secretions of 97% of study participants at baseline. It continued to be detectable in 13% after three months of treatment, and 14% after six months of antiretroviral therapy.

At baseline, HIV was detectable in the vaginal fluids of 86% of women. After three months, the proportion with detectable virus had fallen to 34%, and changed little (36%) after six months.

A total of 69 women had an undetectable viral load in their blood after six months of treatment. Seven (10%) of these individuals had detectable HIV in their cervical fluids and 32% in their vaginal secretions.

In contrast, of the 26 women with a plasma viral load of 100 copies/ml or more at the end of the study, the proportion with virus detectable in cervical and vaginal secretions was 23% and 46% respectively.

Virus levels in both cervical (p = 0.06) and vaginal (p = 0.05) fluids were correlated with viral load in the blood, and were higher when plasma viral load was higher.

Statistical analysis showed that adherence was the strongest predictor of cervical viral load suppression at both months three and six. It remained significant even after adjustment for plasma viral load (p < 0.01).

Similarly, adherence was strongly associated with suppression of HIV in vaginal fluids at both time periods (p < 0. 01). Having a baseline CD4 cell count below 100 cells/mm³ increased the risk of having detectable virus at six months (p = 0.03), as did resistance to antiretrovirals (p = 0.03).

“Our results demonstrated a strong and continuous association between ART adherence and genital HIV-1 shedding”, comment the investigators.

They conclude, “optimizing adherence may therefore be important as a means of…maximizing the effect of ART for reducing the risk of HIV-1 transmission.”