Herpes and HIV

Herpes and HIV

Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2.

Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. Celum et al conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, >/=250 cells per cubic millimetre) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrolment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimetre. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per millilitre (95% CI, 0.22 to 0.29; P<0.001)>The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per millilitre and a 73% reduction in the occurrence of genital ulcers due to HSV-2.

: Given that the majority of people with HIV infection also have herpes simplex-2 (HSV-2) infection, genital shedding of herpes occurs on up to 30% of days in co-infected people living with HIV even when they have no symptoms, and HSV-2 reactivation without symptoms has been associated with increased HIV viral load in the blood plasma and genital tract, there was good reason to conduct a large trial of serodiscordant couples to see if herpes suppression would reduce HIV transmission. After all, five trials had already shown that daily suppressive therapy for HSV-2 reduced plasma HIV viral load. Of 6543 HIV-discordant couples screened, 3408 were enrolled at 14 sites in Botswana, South Africa, Zambia, Kenya, Rwanda, Tanzania, and Uganda. With adherence to acyclovir/placebo high and HIV infections acquired outside the couple excluded from the final analysis through genotyping to link transmitted viruses, this well-powered trial gave an unequivocal answer. Despite reductions in HIV viral load, acyclovir did not reduce HIV transmission. However, this study documented a 16% reduction in disease progression for those in the acyclovir arm, all of whom started the study with CD4+ counts above 250. This suggests that, for their own health, co-infected people who are not yet eligible for antiretroviral treatment may benefit from daily acyclovir – it is off-patent and cheap and has few side effects.