Aciclovir reduces disease progression and death in people with HIV by nearly 20 per cent

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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.

Glossary

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

disease progression

The worsening of a disease.

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

serodiscordant

A serodiscordant couple is one in which one partner has HIV and the other has not. Many people dislike this word as it implies disagreement or conflict. Alternative terms include mixed status, magnetic or serodifferent.

herpes simplex virus (HSV)

A viral infection which may cause sores around the mouth or genitals.

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.

Further information

A webcast of the conference session in which Jairam R Lingappa and Connie Celum presented is available on the IAS 2009 website.