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 <
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
They conclude, “optimizing adherence may therefore be
important as a means of…maximizing the effect of ART for reducing the risk of