HIV positive people given 400mg of aciclovir twice-daily as part of a trial to see if the drug reduced HIV transmission in serodiscordant couples were 17% less likely to progress to AIDS, to have to start antiretroviral therapy, or die, the Fifth IAS Conference was told on its final day. This effect was statistically significant (p=0.03).
This result came out of the Partners in Prevention Study, which failed to find that giving aciclovir to people with HIV reduced HIV transmission to their partners (Celum). But study investigator Dr Jairam Lingappa said that the drug might nonetheless have a role in delaying the initiation of HAART.
The Partners in Prevention study gave 400mg of aciclovir or placebo twice daily for 24 months to 3408 people, two-thirds of them women, who were the HIV- positive partners in a serodiscordant relationship. The average age of women in the study was 29 and of men 37, and the average CD4 count was 480 cells/mm3 in women and about 420 cells/mm3 in men.
Although aciclovir did not reduce HIV transmission, patients on aciclovir were 24% less likely to die from non-traumatic causes (i.e. not because of accidents or violence), though this was not statistically significant (p=0.29). They were 19% less likely to start HAART (p=0.06) or develop a CD4 count under 200 (p=0.05).
Gender, baseline CD4 or baseline viral load made no difference to progression, but there was a trend towards association with good adherence: people who took more than 90% of their doses were 23% less likely to progress to the composite endpoint than average, and people who took less than 90% were 11% more likely to progress (p=0.13).
Could HSV-2 suppression slow HIV disease progression in HIV-infected persons not eligible for ART by current national guidelines, Dr Lingappa asked?
Although the 17% reduction in progression observed was not spectacular, it might be combined with other inexpensive interventions such as co-trimoxazole (Septrin) PCP prophylaxis, which in studies reduced HIV mortality by 45%, and multivitamins, which reduced it by 27%. Based on these findings, aciclovir could delay median time to a CD4 count below 350 cells/mm3 by 6.3 months (28.8 versus 35.1 months).
Audience members commented that the proposal sat uncomfortably with the idea of getting as many people on HAART as possible in order to reduce transmission.
“You have an intervention which prolongs time off antiretroviral therapy but fails to suppress transmission,” said one.”Isn’t that a problem if all it does is prolong the period people are infectious?”
Another audience member criticised the exclusion of pregnant women from the study, since aciclovir has a very safe record in pregnancy, and pregnancy might be a good marker for unprotected sex.
“These findings support the concept of non-ART medications delaying HIV disease progression in HIV infected persons with high CD4 counts,” commented Dr Lingappa.
Additional data will be available from an ongoing trial of herpes suppression in people with CD4 counts between 300-400 which is being conducted in Rakai, Uganda. Further cost effectiveness analyses and modelling studies were also needed, he said.
Lingappa JL et al. Daily acyclovir delays HIV-1 disease progression among HIV-1/HSV-2 dually-infected persons: a randomized trial. . 5th conference on HIV Pathogenesis, Treatment and Prevention, Cape Town. Abstract WELBC102. 2009.
Celum C et al. Twice-daily acyclovir to reduce HIV-1 transmission from HIV-1 / HSV-2 co-infected persons within HIV-1 serodiscordant couples: a randomized, double-blind, placebo-controlled trial. 5th conference on HIV Pathogenesis, Treatment and Prevention, Cape Town. Abstract WELBC101, 2009.