A Triple Winner

Last year, a groundbreaking international trial known as HPTN052 drew worldwide attention when it found that earlier ARV treatment of HIV-infected individuals led to a dramatic 96% decrease in HIV transmission to the uninfected partners in serodiscordant relationships (see VAX July 2011 Spotlight, An Antiretroviral Renaissance). The study also found that earlier treatment delayed the time to AIDS-defining events and tuberculosis and significantly decreased the incidence of clinical events for those with HIV.

An analysis of the HPTN052 study, presented this week at the 19th International AIDS Conference, suggests that early treatment makes sense financially, at least in this population, while a second analysis bolsters even further the data that early treatment improves clinical outcomes. 

“Early ART therapy is a triple winner,” said Harvard University professor Rochelle Walensky and a member of the Cost Effectiveness of Preventing AIDS Complications, who modeled the cost-effectiveness of implementing early treatment to serodiscordant couples using ART and behavioral data from the South African and Indian cohorts enrolled in HPTN052. 

The findings from her team, presented on Friday morning, evaluated the five-year and lifetime benefits of early treatment if implemented in a serodiscordant population. The researchers cautioned that the results may not apply to other risk groups and cannot be generalized for the larger AIDS population.
 
Walensky’s team concluded that early treatment saves lives and money by preventing costly opportunistic infections and preventing HIV transmissions. They determined the strategy—sometimes referred to as test-and-treat—to be cost effective using a ratio that compared the annual cost of ARVs per person to the per capital GDP of the respective countries analyzed. 

Early ARV was determined to be cost-effective if it was less than 3% of the per capita GDP, which it was in both countries. In the case of South Africa, Walensky said the model suggests early treatment may even be a cost-savings because clinical care is far more expensive than it is in India.  

A separate analysis, presented on Thursday, provided a more extensive comparative analysis of both the primary and secondary clinical outcomes from immediate vs. delayed treatment. Those randomized to the delayed treatment arm started therapy after their CD4+ T cell reached 250, others did not begin treatment until their CD4+ T cell count dropped below 250.
 
Early findings reported last year from the HPTN052 trial found early ARV treatment was associated with a longer time to HIV disease and preservation of the immune system over two years. The updated analysis, presented yesterday by Beatriz Grinsztejn, an AIDS scientist with the Instituto de Pesquisa Clinica Evandro Chagas in Brazil, offered a much more extensive look at the clinical outcomes and also included about three months of additional data from what had previously been reported. 

Principal Investigator Myron Cohen noted that the HPTN052 study was originally designed to examine the impact of earlier treatment on primary and secondary clinical outcomes. It was later on that the endpoints of the trial expanded to include HIV transmission rates. He noted that the HPTN052 trial is still ongoing, and that even more extensive data on the clinical benefits of early treatment will be forthcoming. 

In this most recent analysis, those who delayed therapy developed various AIDS defining illnesses—notably tuberculosis—far more rapidly than those who started therapy right away. There were 34 cases of tuberculosis in the delayed treatment arm compared to 17 in the immediate treatment arm. The study also found 19 cases of so-called Stage Four events—an array of 11 different opportunistic infections ranging from preumocystis carinii pneumonia to HIV wasting—in the delayed treatment arm compared to nine in the immediate treatment arm. 

The study also looked at a host of secondary clinical events ranging from malaria to upper respiratory infection, and found with the exception of hypertension, where there were 12 cases in the immediate arm compared to nine in the delayed treatment arm, the rates were all higher among those who delayed treatment. In some instances, such as with herpes zoster, the range was striking: 53 cases vs. 17 cases. 

The analysis also compared the clinical outcomes of five non-AIDS related conditions—liver disease, end-stage renal disease, non-AIDS malignancy, diabetes and cardiovascular disease—and found the incidence rare but similar in both arms.