02/11/10

UNITED STATES:  Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2

Among those infected with both HIV-1 and herpes simplex virus type 2 (HSV-2), daily acyclovir treatment provides a dramatic reduction in occurrence of genital ulcers from HSV-2, but does not reduce transmission of HIV-1 itself, authors of the current study report.

Investigators followed 3,360 couples in 14 sites in Africa. Only one member of each couple was HIV-positive - 68 percent of whom were women - and that partner was also infected with HSV-2. Infected partners were evenly assigned at random to take either acyclovir 400 mg twice daily or placebo.

During the 24-month study period, 132 HIV seroconversions were reported among the previously uninfected partner. Of these, 84 infections were determined to be from the study partner; 38 were not genetically linked as determined by viral sequencing, and 10 other transmissions were lost to follow up for other reasons.

Of the 84 transmissions, 41 were in the group treated with acyclovir (hazard ratio 0.92; 95 percent CI 0.60 to 1.41; P=0.69). Consistent with previous findings, partners who were uninfected with HIV-1 but positive for HSV-2 at the start of the study were at increased risk for becoming HIV-1 positive compared to those without HSV-2 (hazard ratio 2.02; 95 percent CI 1.15 to 3.57).

The authors suggest that the lack of efficacy of acyclovir in suppressing HIV-1 transmission is not due to poor activity of the treatment against HSV-2, as treatment reduced the occurrence of genital ulcers by 73 percent. In addition, they discounted the likelihood of noncompliance, as acyclovir reduced mean plasma concentration of HIV-1 by 0.25 log10 copies/mL (95 percent CI 0.22 to 0.29; P less than 0.001).

The results suggest that a greater reduction in HIV-1 levels is needed to reduce the risk of transmission, the authors said. "This indication 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 (e.g., malaria or helminthic infection), and in the development of HIV-1 vaccines directed at reducing the HIV-1 viral load."

Source: New England Journal of Medicine Vol. 362; No. 5: P. 427-439 (02.04.10):: C. Celum and others for the Partners in Prevention HSV/HIV Transmission Study Team; Courtesy of the CDC National Center for HIV, STD, and TB Prevention