July 23, 2009

HIV Treatment Effective Without Laboratory Monitoring in Southern Africa Study

Regular laboratory monitoring isn’t necessary for making sound antiretroviral (ARV) treatment decisions in resource-poor areas, according to data from the largest clinical trial for people with HIV ever conducted in sub-Saharan Africa. Authors of the Development of Antiretroviral Therapy in Africa (DART) study—reported on Tuesday, July 21, at the Fifth International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town—conclude that many more people with HIV in Africa could be treated for the same amount of money as is currently spent if lab tests are not routinely used to monitor the effects of ARV treatment.

The DART trial began six years ago when treatment for people living with HIV was just starting to become more widely available in Uganda and Zimbabwe, the two countries where the study was conducted.

Sponsored by the U.K. Medical Research Council, the U.K. Department for International Development and the Rockefeller Foundation and presented at IAS by James Hakim, PhD, of the University of Zimbabwe Medical School Clinical Research Centre, DART sought to determine whether the lab-based strategies used to deliver ARVs to people with HIV infection in resource rich countries were essential in Africa, where about 4 million people still need ARVs urgently and resources are limited.

The study enrolled 3,316 people living with HIV; none had been on ARV therapy previously. All had severe or advanced HIV infection and had been assessed for study eligibility using clinical staging—symptoms of HIV/AIDS necessitating treatment, as defined by the World Health Organization—and laboratory tests including CD4 counts (fewer than 200 cells was an entry requirement).

All study volunteers were randomly allotted to one of two study groups. All patients received combination ARV therapy—either Combivir (zidovudine/lamivudine) plus Viread (tenofovir), Viramune (nevirapine) plus Combivir or Combivir plus Ziagen (abacavir)—and had blood drawn regularly for CD4 counts and other lab tests to look for side effects.

In the first study group, health care providers were permitted to recommend changes to a patient’s treatment based on laboratory test results along with WHO-defined symptom staging (specifically a new stage 4 event, such as unexplained weight loss, a diagnosis of Pneumocystis pneumonia or recurrent bacterial infections). In the second group, doctors used WHO staging only to determine if a switch to a second-line treatment regimen was necessary—the standard approach in many resource-poor areas. As a safety net, however, providers in the second group would have been given the results of seriously abnormal laboratory tests, such as dangerously elevated liver enzymes or severe anemia.  

The results showed that 90 percent of people in the first group were still alive after five years of follow-up, compared with 87 people of people in the second group—a difference of only 3 percent.

Over the five years data were collected, 78 percent of people in the first group survived and had developed no new AIDS-related illnesses, compared with 72 percent in the second group. Statistically speaking, this translated into a 30 percent greater risk of a new AIDS-related event among those who received clinical monitoring only, compared with those who received both clinical and laboratory monitoring. In absolute terms, however, Hakim’s group said this degree of increased risk was very small.

No difference in the occurrence of side effects caused by ARV therapy was found between the two groups.

“The health economists in the DART team who have analyzed the trial data have concluded that a third more people could be successfully treated for HIV in Africa if expensive lab tests weren’t used routinely,” Hakim said. “DART has shown that giving [ARV therapy] without these routine tests is safe and effective and suggests how the limited funding available could be used most effectively…. By treating more people, the number of deaths and disease related to HIV infection can be reduced. The challenge now is for policymakers to widen availability of [ARVs].”

This conclusion, however, is likely to stir some debate, as several other research teams—including those presenting data at IAS—have argued the need for more, not less, laboratory monitoring in resource-poor nations. For example, there have been demands for viral load monitoring to help clinicians detect virologic failure while on a first-line treatment, as early as possible, to prevent the accumulation of HIV drug-resistance mutations that will likely limit the effectiveness of second- and third-line regimens.

Whether or not DART—technically a short-term study for a disease in which people can potentially live decades if effectively treated—is enough to settle this controversy remains to be seen.

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