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Acyclovir ineffective in serodiscordant couples.

Acyclovir therapy does not reduce the risk of HIV-1 transmission in people with concurrent herpes simplex 2 infections, according to results from a randomized, placebo-controlled trial of 3,360 couples from 14 sites in Africa.

The drug does, however, reduce the HIV-1 viral load and the risk of developing HSV-2 genital ulcers. Acyclovir lowered the mean plasma concentration of HIV-1 RNA by 0.25 [log.sub.10] copies/mL, but this was not enough to prevent transmission any better than placebo did, Dr. Connie Celum and her coauthors wrote.

"The lack of efficacy ... in our study suggests that a greater reduction in HIV-1 levels is needed to reduce the risk of transmission," wrote Dr. Celum of the University of Washington, Seattle, and her associates.

The determination that "a greater reduction in the plasma viral load may have to be achieved provides information that can be useful in the development of other biomedical strategies for the prevention of HIV-1, such as the treatment of coexisting infections "and in the development of HIV-1 vaccines directed at reducing the HIV-1 viral load," they commented.

In each couple participating in the study, one partner was infected with both HIV-1 and HSV-2 at enrollment and not taking any antiretroviral drugs; the other partner was free of HIV-1, but 68% also had HSV-2 (N. Engl. J. Med. 2010;362:427-39).

HIV-1 infected partners were randomized to placebo or 400 mg acyclovir twice daily. The study's main end point was HIV-1 transmission after 24 months.

Most of the infected partners (68%) were women. Ages varied widely, from 18 years to older than 36 years. Couples had been together for a median of 5 years; most (90%) were living together and 76% were married.

Among partners infected with HIV-1, the median CD4 count at baseline was 462 cells/[mm.sup.3]. The median HIV-1 plasma RNA levels were 3.9 [log.sub.10] copies/mL in women and 4.3 [log.sub.10] copies/mL in men. At baseline, 23% of the HIV-1 infected partners had experienced a genital ulcer outbreak within the past 3 months; 3% had ulcers at baseline.

Couples were seen monthly for pill distribution and counseling. At every visit, both received intensive counseling on risk reduction, free condoms, and treatment for any sexually transmitted disease. Full 24-month follow-up occurred in 92% of the infected partners and 84% of the non-infected partners. The study accumulated 4,868 person-years of follow-up.

Seroconversion to HIV-1 occurred in 132 initially noninfected partners, an overall incidence of 2.7/100 person-years. Of these new infections, 38 were not genetically linked to the infected partner, reflecting HIV-1 transmission from a different person. Three transmissions could not be genetically classified; six were excluded because the women became pregnant and stopped taking the study drug; and one was excluded because an incorrect drug was dispensed.

Thus, 84 new HIV-1 infections genetically linked to the study partner were included in the intention-to-treat analysis. The overall transmission rate was 1.8/100 person-years. Males, with a transmission rate of 2.5/100 person-years, were 65% more likely to transmit the disease to females than females were to males, Dr. Celum and her associates reported.

Of the 84 new infections, 41 occurred in the acyclovir group and 43 in the placebo group, a nonsignificant difference. The difference remained nonsignificant when the investigators included all transmissions.

Acyclovir, however, did significantly lower the HIV-1 viral load, compared with placebo. The mean plasma concentration of HIV-1 during the follow-up period was 0.25 [log.sub.10] copies/mL lower in the active group than in the placebo group.

Medication adherence played a role, with a reduction of 0.16 [log.sub.10] copies/mL in those who were less than 75% adherent, and 0.27 [log.sub.10] copies/mL in those who were at least 90% adherent, Dr. Celum and her associates reported.

Acyclovir also reduced outbreaks of genital ulcers by 61%, compared with placebo (217 episodes vs. 550 episodes; risk ratio 0.39).

There were no adverse events related to acyclovir treatment. The overall transmission rate in the study (2.7/100 person-years) is less than the rate reported in other observational studies of a similar population, the authors noted.

"It is likely that the lower rate in our study was due largely to our having provided monthly counseling on risk reduction, free condoms, and other preventive services," Dr. Celum and her associates said.

They recommended that serodiscordant couples always receive counseling about safe sexual practices, especially when engaging in sex with a partner outside the relationship whose HIV status is unknown.


Major Finding: A daily regimen of 800 mg acyclovir did not prevent HIV-1 infection in serodiscordant couples.

Data Source: A randomized, controlled trial of 3,360 HIV-1 serodiscordant couples in Africa.

Disclosures: The study was funded by grants from the Bill and Melinda Gates Foundation and the University of Washington, Seattle. Dr. Celum reported receiving grant money and serving on an advisory board for GlaxSmithKline.
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Author:Sullivan, Michele G.
Publication:Internal Medicine News
Article Type:Report
Geographic Code:1USA
Date:Feb 15, 2010
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