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Vaginal bacteria increase HIV susceptibility and may reduce PrEP effectiveness
Liz Highleyman, 2016-08-15 07:40:00
Overgrowth of a certain species of vaginal bacteria
was associated with a 13-fold higher likelihood of becoming infected with HIV,
while another species was found to lower tenofovir levels and may contribute to
reduced efficacy of pre-exposure prophylaxis (PrEP) delivered in a vaginal gel,
according to a set of presentations at the 21st International AIDS Conference (AIDS 2016) last month in Durban, South Africa.
The continuing high rate of HIV incidence among women
and girls was a key theme at AIDS 2016. Women and girls account for nearly 60%
of newly infected people in sub-Saharan Africa, conference co-chair Olive
Shisana noted in her opening remarks.
At a session on "New Evidence: Why Do Young Women in Africa Have High
Rates of HIV Infection?" Quarraisha Abdool Karim from
the Centre for the AIDS Programme of Research in South Africa (CAPRISA)
explained that both social and biological factors play a role.
For example, a phylogenetic study of
transmission dynamics in South Africa found that many young women in their
teens or twenties acquire HIV from men who are 8 years older, on average, and
not on antiretroviral therapy. The older men were themselves infected by women their
own age, and in an on-going cycle the younger women grow up to pass the virus
on to men in their age group.
Other CAPRISA researchers focused on factors that may
increase biological susceptibility to HIV infection.
Jo-Ann Passmore of the
University of Cape Town and Brent Williams of Columbia University looked at
vaginal bacteria samples from 119 South African women who participated in the CAPRISA 004 trial, which
tested a 1% tenofovir vaginal gel for HIV prevention. The main study, reported in 2010, found that the gel reduced HIV acquisition by
39% overall and by 54% among women with good adherence.
The researchers compared
bacterial genetic material from women who acquired HIV and those who remained
uninfected. The CAPRISA team previously reported that women with a greater
degree of genital inflammation were significantly more likely to become
They found that women who
carried the uncommon bacteria Prevotella bivia were 19 times more likely
to have genital inflammation and 13 times more likely to contract HIV than
those with little or none of this bacteria. Among the 22 women with genital
inflammation who became HIV-positive, 41% had P bivia.
These bacteria produce lipopolysaccharide (LPS), which acts as a toxin to stimulate immune activity and promote
genital inflammation, raising levels of
pro-inflammatory cytokines and attracting CD4 cells that are vulnerable to HIV
In a related study, Adam Burgener of the Public Health Agency of Canada
and Nichole Klatt of the University of Washington analysed genital bacteria samples from 688
CAPRISA 004 participants, of whom half used the tenofovir gel and half used a
They found that among women with
a healthy vaginal microbiome, characterized by a predominance of Lactobacillus
species, the protective effectiveness of the vaginal gel was 61%, compared with
just 18% when Lactobacillus made up less than half of vaginal bacteria.
In laboratory studies they showed
that tenofovir levels remained high in the presence of Lactobacillus,
but when Gardenerella vaginalis was
predominant – a condition known as bacterial vaginosis – tenofovir was sequestered in cells and
rapidly depleted in the surrounding fluid.
"Gardnerella just gobbled it up," CAPRISA director Salim
Abdool Karim said at an AIDS 2016 press conference.
These findings may help explain
the disparity in PrEP efficacy between men and women – which does not appear to
be entirely due to lower adherence – and raise the possibility that either
killing off harmful bacteria or introducing beneficial bacteria could lower
women's risk of HIV infection.
HIV infections in young women is one of the greatest challenges in
Africa," Salim Abdool Karim said in an AIDS 2016 press release
. "Based on our results,
implementing targeted prevention interventions to break the cycle of HIV
transmission while effectively treating bacterial vaginosis could reverse the
devastating impact of the HIV epidemic in young people in Africa."