New Data Redefining Laboratory Reference Ranges in Africa

SEATTLE, August 21, 2007 ─ Leading researchers from the International AIDS Vaccine Initiative (IAVI), the U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Military HIV Research Program (USMHRP) presented final results today from a collection of independent studies reexamining the medical criteria for including African volunteers in AIDS vaccine trials. The findings, presented at the AIDS Vaccine 2007 Conference in Seattle, suggest that many healthy Southern and East Africans have, in the past, been excluded from participating in trials based on laboratory reference ranges that were developed for Western populations and may not be appropriate locally. Implementation of the results of the studies should improve participation of African volunteers in clinical trials for new drugs and vaccines against emerging infectious diseases currently ravaging Africa, including AIDS, TB and malaria, and enable clinicians to better monitor and define adverse events in trials.

In the first reference range studies conducted on such a large scale, researchers from the involved organizations examined the blood tests of approximately 5,500 clinically healthy HIV-negative volunteers across a dozen clinical sites in four African countries. For some markers, the studies revealed differences between the norms usually found in healthy Africans and the reference values developed for populations in North America and Europe.

“These studies are important for a range of research on neglected diseases, from HIV vaccines to malaria and TB drug therapy,” said Anatoli Kamali, an epidemiologist with the Medical Research Council/Uganda Virus Research Institute and the Protocol Chair of the IAVI-sponsored study. “For the first time, African volunteers seeking to participate in trials will now be evaluated according to blood reference ranges that accurately reflect their populations. Furthermore, we will now be able to interpret laboratory abnormalities detected during vaccine or drug clinical trials more accurately in Africa.”

“We’re excited about these findings. Localized reference parameters could significantly help us to improve recruitment for clinical trials in less-industrialized nations, as well as better evaluate the health of our volunteers throughout the course of these studies,” said Mark de Souza, Director, International Laboratory Program, USMHRP. In one of its trials in Uganda, the USMHRP screened out 58% of potential participants because of lab abnormalities using Western ranges. In a second trial, the screen-out rate decreased to 23% using a norm localized for the trial site. In addition, says de Souza, “With local ranges, we can better detect reactions to candidates, enlist a more typical cohort in the trial and thus test it on the most representative group of volunteers, possibly significantly accelerating the search for HIV vaccines for those countries hardest hit by the epidemic.”

As part of their two-year study, IAVI and its partners examined blood chemistry and hematology parameters, as well as evaluated kidney and liver functions and the immunological health of thousands of volunteers. Individuals with clinical symptoms or abnormal physical exams and anyone infected with HIV, hepatitis B or C, or untreated syphilis were excluded from the study. “These studies should be valuable to anyone designing trials of preventive medicines or vaccines for these parts of Africa,” concluded Pat Fast, Executive Director of Medical Affairs, IAVI. “Improving participation in AIDS vaccine trials among populations in desperate need of new AIDS technologies is the first step in ultimately reaching our goal of ending the AIDS crisis.”

Currently, Africa remains the epicenter of the AIDS pandemic with 2.8 million new infections annually. In 2006 alone, almost two-thirds (63%) of all persons infected with HIV were living in sub-Saharan Africa. IAVI and partners, as well as CDC and the USMHRP, and other international organizations plan larger-scale trials of promising vaccine candidates over the coming years in the Eastern and Southern region of Africa and elsewhere.