Featured news from NHIVNA
HIV-related news from NAM
Open-label PrEP in Botswana: very high adherence and no HIV infections seen
Gus Cairns, 2015-08-05 13:50:00
A study of open-label Truvada
HIV pre-exposure prophylaxis (PrEP) in Botswana among heterosexual people found
very high adherence rates. Around 90% of participants had useful levels of
the drug in their blood; there was a high concordance between self-reported adherence and
drug levels; and there were no HIV infections, the Eighth International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention (IAS
2015) was told last month.
The participants had all previously taken part in the TDF2 placebo-controlled
study of PrEP which took place between 2007 and 2011 and found an
efficacy of 62% for PrEP versus placebo.
For the present study, attempts were made to contact all the
1219 participants in the original TDF2 study. Presenter Faith Henderson of the
US Centers for Disease Control and Prevention (CDC) commented that, with a three-year gap and a
highly mobile population in Botswana, it was hard to contact all participants.
However, 736 TDF2 participants (60%) were eventually traced. Of these, 229 (31%)
were eligible to take PrEP using the same criteria as the original TDF2 study –
which, in this very high-prevalence country, were that they were between 19 and
39 years old (90% in TDF2 were in fact in their 20s) and were sexually active.
The main reasons for exclusion were that the person was now HIV positive, had
blood results indicative of kidney disease or, for women, that they were
pregnant or breastfeeding.
condoms were dispensed once a month and participants were tested for HIV and
received risk-reduction counselling once every three months. Participants also
received text messages or phone calls as adherence reminders.
Of the 229 people enrolled, 60% completed ten or more of
the maximum of twelve monthly study visits and the number of patient-years of
data collected was 76% of the possible maximum. Fifty-six per cent of
participants were male, and women were about 60% more likely not to complete
the study – the reasons why are being investigated in qualitative studies. The only
other factor associated with non-completion was that people who experienced
significant side-effects were twice as likely not to complete the study.
The open-label study was primarily designed to measure any
behavioural change and also to measure adherence. Averaged over each monthly
visit, 71% of participants reported only one sexual partner in the previous month,
9% two and 2.4% three or more (not all participants reported number of partners).
The average number of sexual partners in the previous month stayed at about one
for men during the study, but declined from one to about 0.75 in women. The
average number of self-reported condomless sex acts in the previous month
declined from 1.9 to 1.2 in men and from 1.45 to 0.95 in women.
Self-reported adherence was high. When asked if they had
taken Truvada in the last three days
before their clinic visit, 88% said they had taken it all three times, 5.5%
once or twice and 6.7% had taken none.
Altogether, 120 completing participants (52%) had drug
levels measured in blood samples for tenofovir. Among these, 100% had tenofovir
levels over five nanograms per millilitre (ng/ml), indicative of some use in
the last week, and 94% over 25ng/ml, indicating clinically useful levels.
These levels were concordant with self-reported adherence: in samples from participants who
said they had taken all three pills in the last three days, drug levels were
over 25ng/ml in 92% of women and 98% of men; if two doses were reported, drug
levels were over 25ng/ml in 90%; if once in the last three days, 86.5%; and if
no doses were reported in the last three days, 42% of women and 73%
of men had levels over 25ng/ml.
In a subset of 30 participants, the proportion of people with
levels over 25ng/ml were 93%, 93%, 100%, 93% and 90% at months one, three,
six, nine and twelve of the study, so there was no or little evidence of any
falling-off in adherence. Women were 9% less likely than men to have clinically
useful tenofovir blood levels and people who did not report any condomless sex
also had slightly lower adherence, though this difference was not significant.
No HIV infections occurred in any study participant. Although
this was not designed as an efficacy study, five or six HIV infections would
have occurred if background HIV incidence was at the rate seen in the placebo
arm of the original TDF2 study (3.1% a year).
Further drug level analysis and qualitative data will be
presented, but – although there must be a big caveat about the use of text and
phone reminders in this study – it does show that high and effective
adherence levels to PrEP can be reached among an African heterosexual population
who are in need of it.
The big question now is whether the Botswana
government and other agencies will extend their already impressive level of
antiretroviral therapy provision to people with HIV to cover PrEP provision for
the proportion of HIV-negative people who remain at significant risk.