ROME — In a clinical trial that dramatically confirmed years of observation, early use of antiretroviral therapy reduced the risk of transmitting HIV between couples. the approach also reduces the risk of clinical symptoms of HIV infection, although not to the same degree, according to Myron Cohen, MD, of the University of North Carolina Chapel Hill, and colleagues. the findings support the use of antiretroviral therapy as a public health measure to slow the rate of HIV transmission, Cohen and colleagues reported online in the new England Journal of Medicine and at the International AIDS Society conference here.Action Points  

• Explain that in a clinical trial that dramatically confirmed years of observation, early use of antiretroviral therapy reduced the risk of transmitting HIV between couples.
• Note that the approach also reduces the risk of clinical symptoms of HIV infection.

“The study demonstrates a terrific benefit from earlier therapy,” Cohen told MedPage Today. “It’s quite simple – there’s a clinical benefit for the patient and a dramatic, nearly 100%, reduction in transmission.”

The key question now, he added, is how to best use the knowledge to slow the progress of the HIV/AIDS pandemic.

That’s especially true because “we don’t have enough resources” to treat all those for whom therapy is clinically indicated, according to Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

“With the resources we have, we can’t do everything,” he said, so the question is how to use the findings to have the most impact.

Sustained suppression of HIV in genital secretions is the “most likely” explanation for the reduction in transmission observed in the HIV Prevention Trials Network (HPTN) 052 study, Cohen and colleagues concluded.

The HPTN 052 trial enrolled 1,763 couples, in nine countries, in which one partner was HIV–positive and the other was not. the HIV-positive partners all had relatively robust immune systems and antiretroviral therapy was not indicated according to guidelines.

The HIV-positive partners were randomly assigned to get triple-drug antiretroviral therapy or to wait until the treatment was indicated, with the hypothesis that members of the early-treatment group would be less likely to transmit the virus to their uninfected partners.

A clinical hypothesis was that those getting early treatment would also have a lower risk of serious HIV symptoms: Pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.

The HTPN 052 trial was designed with enough statistical power to show a 20% reduction in the risk of transmission, but it was stopped early when an interim analysis showed the risk reduction was 96%, Cohen and colleagues reported.

Indeed, of the 28 transmissions that were genetically linked to the infected partner, only one took place in the early-treatment group (HR 0.04, 9% CI 0.01 to 0.27, P<0.001), they found.

There were 39 cases of HIV transmission, including 11 that could not be linked to the infected partner, the researchers reported. of those, only four were in the early treatment group. the hazard ratio was 0.11 with a 95% confidence interval from 0.04 to 0.32, which was again significant at P<0.001.

Cohen told reporters that the single case of transmission was at best equivocal: the initially uninfected partner was shown to have acquired HIV 85 days after her partner began therapy, but genetic analysis suggested she had been infected more than 50 days and as much as 84 days earlier.

“Our interpretation is that it’s very likely that transmission took place before her partner had enough antiviral to suppress viremia,” Cohen said.

There was also a benefit of early treatment in terms of the primary clinical endpoints, Cohen and colleagues reported. There were 40 such events in the early-therapy group and 65 in the delayed-therapy group (HR 0.59, 95% CI 0.40 to 0.88, P=0.01).

The difference was mainly driven by the incidence of extrapulmonary tuberculosis, seen in three participants in the early-therapy group and 17 in the delayed-therapy group, a difference that was significant at P=0.002.

There was no significant difference between the groups in incidence of pulmonary tuberculosis, they found.

The researchers also reported:

• 82% of the 28 linked transmissions took place in Africa.
• In 18 of the 27 cases in the delayed-treatment group, the source of HIV was a woman; the source of the sole transmission in the early-treatment group was a man.
• 55% of the cases of extrapulmonary tuberculosis were seen in India.
• 97% of the couples were heterosexual and 94% were married.
• 50% of HIV-positive participants were men.
• There were 23 deaths, including 10 in the early-therapy group and 13 in the delayed-therapy group, a difference that was not significant.

Aside from the primary clinical endpoints, 246 HIV-positive participants had one or more severe or life-threatening adverse events, but there was no significant difference between the groups.

The report comes as a series of recent results, including the HPTN 052 trial, has provided “strong encouragement” for the use of antiretroviral drugs to prevent HIV infection, according to Scott Hammer, MD, of Columbia University in new York City.

They include the use of a microbicide gel, containing an anti-HIV drug, to reduce the risk of women acquiring the virus, and a study of oral prophylaxis to prevent infection among men who have sex with men, Hammer noted.

HPTN 052 suggests that there is a “dovetailing of individual and public health benefits” that supports such approaches, Hammer argued in an accompanying editorial in the journal.

But drug therapy as prevention “is not the ultimate answer to controlling and ending the HIV epidemic,” he argued, because of such concerns as adverse events, the possible emergence of drug-resistance, and cost.

Nonetheless, Hammer concluded, such an approach has the “potential to preserve health and control the epidemic until a safe and effective HIV vaccine is a reality.”

The study was supported by the HIV Prevention Trials Network and the National Institute of Allergy and Infectious Diseases. Study drugs were donated by Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, and Merck.

The journal said Cohen did not report any disclosures.

The journal said Hammer reported financial links with Merck and Progenics.