Many
experts regarded the results with surprise, since considerable research has shown
that sexually transmitted infections (STIs) that cause genital ulcers are associated
with higher rates of HIV transmission and acquisition. Since herpes simplex type
2 (HSV-2) has been linked to a 2- to 3- fold increase in susceptibility to HIV
-- and since several studies have shown than suppressing HSV-2 significantly reduces
HIV concentrations in both plasma and genital fluid -- it was thought that herpes
treatment would reduce the risk of HIV infection, and some smaller epidemiological
studies suggested that this was the case.
Now, a second large, controlled
study, described in the March 12, 2008 online edition of the New England Journal
of Medicine, has also found that herpes treatment does not appear to offer
protection against HIV infection.
This study included 821 women, aged 16-35
years, who worked at recreational facilities such as bars and guesthouses in northwestern
Tanzania. Participants were interviewed and underwent serological testing for
HIV and HSV-2. Women who were negative for HIV but positive for HSV-2 were randomly
assigned to receive either suppressive herpes treatment using 400 mg twice-daily
acyclovir or else placebo.
Participants attended mobile clinics every
3 months for a follow-up period of 12-30 months. Adherence to treatment was estimated
based on pill counts at each visit, as well as urine tests. Women who became pregnant
during follow-up were excluded from the modified intention-to-treat analysis.
Results
•
659 women (80%) completed follow-up, for a mean period
of 1.52 years for the acyclovir arm and 1.62 years for the placebo group.
•
The median reported adherence was 90% in both arms.
•
The overall incidence of HIV infection was 4.27 per 100
person-years, and did not differ between the 2 arms (27 women in the acyclovir
group, 28 in the placebo group).
•
There was no overall effect of acyclovir on the incidence
of HIV infection (rate ratio for the acyclovir group 1.08).
•
There was a trend toward lower HIV incidence among women
reporting high acyclovir adherence, but this did not reach statistical significance.
•
Genital HSV-2 was detected in a similar proportion of
participants (4%-5%) in the acyclovir and placebo arms at 6, 12, and 24 months.
•
There were 6 episodes of genital ulceration or blisters
in the placebo group compared with 9 in the acyclovir arm (odds ratio 1.69).
•
Serious adverse events were documented in about 10% of
participants in both arms, but none were attributed to acyclovir.
Conclusion
In
conclusion, the study authors wrote, "These data show no evidence that acyclovir
(400 mg twice daily) as HSV suppressive therapy decreases the incidence of infection
with HIV."
In their discussion, the researchers noted that urine tests
showed that many of the women in the acyclovir arm were not taking the drug as
directed, and a substantial proportion had no detectable acyclovir. They suggested
that higher acyclovir doses and better adherence might be more likely to offer
protection against HIV infection.
London School of Hygiene and Tropical
Medicine, London, UK; African Medical and Research Foundation and National Institute
for Medical Research, Mwanza, Tanzania; Laboratoire de Microbiologie, Hopital
Saint Louis and INSERM Unité 743 and Université Paris V, Paris,
France.
3/18/08
Reference D
Watson-Jones, HA Weiss, M Rusizoka, and others. Effect of Herpes Simplex Suppression
on Incidence of HIV among Women in Tanzania. New England Journal of Medicine.
March 12, 2008 [Epub ahead of print].
Results
In
conclusion, the study authors wrote, "These data show no evidence that acyclovir
(400 mg twice daily) as HSV suppressive therapy decreases the incidence of infection
with HIV."
