By Liz Highleyman

Numerous past studies have shown that the presence of sexually transmitted diseases (STDs) increases the risk of both acquiring and transmitting HIV. As such, STD treatment may play an important role in a comprehensive HIV prevention strategy.

As reported at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, taking place this week in Sydney, Australia, researchers provided the latest data from a study looking at the impact on HIV infection of treating herpes simplex virus type 2 (HSV-2) using acyclovir.

Studies have shown promising results with a similar drug, valacyclovir (Valtrex), but the older acyclovir is less expensive.

In the present study, researchers conducted a double-blind, placebo-controlled trial of acyclovir suppressive treatment among 1350 women age 16-35 years working in bars, guesthouses, and similar facilities in Northern Tanzania; of these. All women tested positive for HSV-2 at study enrolment; 821 were initially HIV negative but at high risk for infection, while 484 were HIV positive.

The women were provided with safe sex counseling, condoms, health checks, STD care, and were offered voluntary HIV counseling and testing. In addition, participants were randomly assigned to receive either 400 mg oral acyclovir twice daily (n = 400) or placebo (n = 421).

The women were followed through mobile clinics every 3 months for up to 30 months. After an interim analysis at 12 months found a lower than expected HIV infection rate and a higher than expected drop-out rate (mainly due to women becoming pregnant), the number of participants and the study length were increased to improve the ability to achieve statistically significant data.

Results

• 70% of women reported taking at least 75% of their prescribed acyclovir or placebo tablets during the preceding 3 months.

• Among the HIV positive women, the proportion with detectable HIV in their genital secretions was 20%-25% lower in those taking acyclovir compared with placebo.

• After 30 months, overall, acyclovir had no effect on HIV acquisition among the HIV negative women, as similar infection rates were seen in both the acyclovir and placebo groups.

• In a modified intention-to-treat analysis, the incidence rate of new HIV infections was 4.45 per 100 person/years (PY) in the acyclovir group compared with 4.12 per 100 PY in the placebo group, a non-significant difference (incidence rate ratio 1.08).

• In a strict intention-to-treat analysis, the respective incidence rates were 4.29 and 4.25 per 100 PY, again a non-significant difference (incidence rate ratio 1.01).

• In an on-treatment analysis, 27 women were infected with HIV in each arm, yielding incidence rates of 4.46 per 100 PY in the acyclovir group and 3.99 per 100 PY in the placebo group (incidence rate ratio 1.12).

• However, among women who achieved 90% or better adherence to acyclovir, there were 8 seroconversions (incidence rate 2.52 100 PY) in the acyclovir group compared with 15 (incidence rate 4.32 per 100 PY) in the placebo group -- a trend that did not quite reach statistical significance (incidence rate ratio 0.58).

• Conversely, among women with less than 75% adherence, the corresponding incidence rates were 5.57 and 2.24 per 100 PY (incidence rate ratio 2.48)

• About one-quarter of the women stopped taking the study drug; this was due to pregnancy in 79%.

• The frequency of severe adverse events were similar in the acyclovir and placebo groups.

Conclusions

The researchers concluded that overall, acyclovir appeared to have no effect in reducing HIV acquisition. However, though the numbers were small, it may have had some protective effect in lowering the risk among women with the best adherence. In addition, the lower rates of HIV In vaginal secretions among the women taking acyclovir may reduce their likelihood of infecting sexual partners or infants during delivery

"Persuading women to take acyclovir twice a day for 2 years or more, when they are basically healthy, is obviously difficult," said lead author Deborah Watson-Jones. "We were unable in this long-term trial to maintain the very high levels of treatment adherence of over 90% reported in shorter trials."

In addition she said during a question period following the presentation that the presence of acyclovir metabolites in urine (tested in only a small subset of women) did not show very good agreement with self-reported adherence.

However, Watson-Jones continued, "[O]ur finding of a protective effect in women with the best adherence, even though not statistically significant, leaves us with hope that this could still be an effective strategy in populations where high adherence can be achieved."

She added that an effective HSV-2 vaccine would be a more practical way of controlling genital herpes, and urged that research in this area be given a higher priority.

African Medical & Research Foundation, Mwanza, Tanzania; London School of Hygiene & Tropical Medicine, London, UK; National Institute of Medical Research, Mwanza, Tanzania.

07/24/07

Reference
D Watson-Jones, M Rusizoka, H Weiss, and others. Impact of HSV-2 suppressive therapy on HIV incidence in HSV-2 seropositive women: a randomised controlled trial in Tanzania. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Sydney, Australia, July 22-25, 2007. Abstract MOAC104.

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