Early HIV treatment is benefit 'trifecta'
Early treatment of HIV before there is sustained damage to the immune system is a "triple winner".
WASHINGTON -- Early treatment of HIV before there is sustained damage to the immune system is a "triple winner," a researcher said here.
A landmark trial has already shown that effective early treatment almost completely prevents HIV transmission in heterosexuals, according to Rochelle Walensky, MD, of Harvard Medical School.
But a new analysis of the same trial, dubbed HPTN 052, also shows that early treatment reduces the risk of both AIDS-defining and non-AIDS clinical events for the treated partner, Walensky said.
And another analysis presented here at the International AIDS Conference demonstrated that – on a broader scale – early treatment is cost-effective over both the short and longer term.
"Early [treatment] is a triple winner," Walensky told reporters. "HIV-infected patients do better, their partners are protected, and it is very cost-effective."
For years, the decision on when to start treatment has been based on the number of CD4-positive T cells in a microliter of blood. The number established by guidelines has slowly increased as evidence has mounted that delayed treatment leads to worse outcomes even if the virus is completely suppressed by therapy.
While that evidence has suggested that early treatment prevents a range of later adverse outcomes, HPTN 052 is the first randomized clinical trial to demonstrate this fact, according to principal investigator Myron Cohen, MD, of the University of North Carolina Chapel Hill.
The findings come as treatment recommendations in the developed world are dropping the CD4 guidepost and suggesting treatment should be offered to anyone with HIV.
In the developing world, however, national guidelines for the most part set the bar at 350 CD4 cells -- those with more cells are not considered eligible for treatment -- and when HPTN 052 was started, the bar was set at 250 cells or even lower.
HPTN 052 enrolled 1,763 heterosexual couples in which one partner had HIV and the other did not.
The HIV-positive partners -- with an average CD4 count of between 350 and 550 -- were randomly assigned to get treatment immediately or to wait until the CD4 count fell below 250 or they suffered an AIDS-defining illness. All told, 24% of those in the delayed treatment arm met the pre-set criteria and started therapy during a median follow-up of 2.1 years.
The primary goal was to see if there would be a difference in transmission between partners in the two arms of the trial, with or without antiretroviral treatment.
The study was stopped early -- and all participants with HIV offered therapy -- when an interim analysis showed that treatment reduced the risk of transmission by 96%.
But during the trial, 134 HIV-positive participants had at least one AIDS-related clinical event, including 26 deaths, and 21 non-AIDS events, according to lead researchers Beatriz Grinsztejn, MD, PhD, of the Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, in Rio de Janeiro.
More of those events took place among those in the delayed-therapy arm, Grinsztejn reported in a late-breaker session. Specifically:
These are good results, commented Gerald Friedland, MD, of Yale University School of Medicine in New Haven, Conn., a session moderator who was not part of the Grinsztejn study.
"It's important to note that there is an advantage" for earlier treatment over delayed therapy, he told MedPage Today.
The effect was modest, probably because the trial was stopped early because of the prevention result, he noted. And it will be important, he said, to know if there is a point in the decline of the CD4 count when the risk suddenly increases or if it is a steady rise as the immune system fails.
In a separate late-breaking presentation, Kenneth Freedberg, MD, of Harvard Medical School, said early treatment can be worth the money it costs and -- in some cases -- might even be cheaper than delaying therapy.
The analysis used cost data from India and South Africa -- two of the countries where the HPTN 052 trial was carried out -- and assumed the same health and prevention benefits as were seen in the trial.
Freedberg noted that the World Health Organization regards a health intervention to be cost-effective if it costs less than three times a nation's per capita gross domestic product (GDP) and to be very cost-effective if it costs less than the per capita GDP.
On that basis, he said, treatment as prevention was either very cost-effective or cost-effective in both countries, depending on the time-frame of the analysis.
For example, the per capita GDP in South Africa is $8,100 (U.S.), while the cost of early therapy over 5 years would be $4,830, making it very cost-effective, he said.
Over a lifetime, the intervention would only be cost-effective -- using the WHO definition -- largely because patients would live longer and therefore would consume more healthcare resources, including drugs and routine care.
The finding is both "important and reassuring that even over the relatively short term this is beneficial," commented Peter Reiss, MD, PhD, of the Academic Medical Center in Amsterdam, who was not part of the study but who moderated a press conference at which some details were presented.
"It's important that these scientific studies are done," he told MedPage Today, "so that decision makers actually have figures on the table."
The HPTN 052 study was supported by the National Institute of Allergy and Infectious Diseases.
Grinsztejn, Freedberg, and Walensky did not make any disclosures. Reiss made no disclosures and Friedland made no disclosures.
By Michael Smith
Primary source: International AIDS Conference Source reference: Grinsztejn B, et al. "Effect of early versus delayed initiation of antiretroviral therapy (ART) on clinical outcomes in the HPTN 052 randomized clinical trial" IAC 2012; Abstract THLBB05.
Additional source: International AIDS Conference Source reference: Walensky RP, et al. "The cost-effectiveness of treatment as prevention: analysis of the HPTN 052 trial" IAC 2012; Abstract FRLBC01.
Source: MedPage Today