According to the World Health Organization, about 9.7 million people living with HIV in resource-poor nations are in desperate need of antiretroviral (ARV) therapy. The high cost of these medications is a major obstacle. Another significant barrier to treatment is limited access to CD4 cell count testing—a much-needed tool in deciding when treatment should be started and possibly whether or not a prescribed regimen is working properly.

In areas that have been hardest hit by HIV—often the poorest and most isolated regions of the world—the scarcity of CD4 technology is no exaggeration. HIV-positive residents of rural Africa, Asia and Latin America speak of traveling more than a hundred miles to the nearest HIV clinic, with many unable to return two weeks later to get the results of their tests or to pick up their medication. Even in cities with a CD4 cell counting machine—called a flow cytometer—electrical outages and limited funds for maintaining and operating the assay can take them off-line for hours or days at a time.

Efforts to reduce the expense of ARV therapy have been well publicized, including the provision of reduced-cost brand-name drugs from pharmaceutical companies and the production of cheap generic equivalents. Out of the spotlight is an equally noble initiative to develop and widely disseminate simple, affordable, rapid and robust CD4 tests for use by mobile health care workers in remote settings.     

Steven Reid, PhD, program director of the CD4 Initiative at Imperial College London, is working on exactly this kind of test. If his group has its way, the point-of-care tests will be in health care workers’ hands by the end of 2010. What’s more, one of the companies the CD4 Initiative is working with might be able to produce an even better test than Reid and his colleagues anticipated.

Funding Innovation

The CD4 Initiative, funded by the Bill & Melinda Gates Foundation, is pairing academic researchers with private companies to develop the inexpensive point-of-care tests. Reid’s group issued requests for proposals and ultimately provided grants to four companies to develop the tests. Three of the funded companies have yielded tangible assays; ultimately, Reid’s team will select one test to move forward.

The widespread availability of a point-of-care CD4 count assay will save lives by saving money. “The current flow cytometry machine is very expensive, up to $100,000 U.S. dollars, and that doesn’t include the cost of the tests, the people who run the tests and all the other ancillary costs,” Reid says.

He adds that such machines require a sterile laboratory and a lot of training to use and maintain. All of this is completely out of reach for most clinics in smaller cities, let alone rural villages.

The CD4 Initiative hopes to make its hand-held tests available for no more than $2 each. Also, the group is shooting for a test of very high quality and accuracy. This could truly revolutionize rural HIV care. “It won’t be perfect,” Reid comments, “but it will be a reasonable alternative, and affordable.”

The CD4 Initiative’s original best hope was a semi-quantitative assay—a rudimentary test that signals when a person’s CD4 count has fallen below a certain threshold, say 200 or 350, and may be a suitable candidate for HIV treatment. Two groups working with the CD4 Initiative—Beckman Coulter and the Burnet Institute—have been successful in this regard.

Expectations were exceeded by the third company, Zyomyx Inc., which developed a fully quantitative assay—“an unexpected and exciting” discovery, Reid says. If proved reliable, this assay would provide health care workers with the actual number of CD4 cells in a patient’s blood sample. Such a test could be used not only to help decide when to start ARV treatment, but also to monitor patients’ immune systems while they’re on therapy.

The only potential shortcoming of the point-of-care CD4 test is its inability to determine when treatment stops working, which is usually determined by a viral load test. In the United States and other resource-rich areas, steady access to expensive viral load technology is needed for this assessment.

A number of studies conducted in sub-Saharan Africa have involved monitoring patients for treatment failure using CD4 counts or the onset of new AIDS-related symptoms alone. There is usually a lag between the time viral load rebounds while on treatment and the time the CD4 cell count begins to decrease—or the individual becomes ill. During this lag time, HIV mutations associated with drug resistance continue to accumulate. And the more mutations a person’s HIV has at the time treatment failure is detected, the less likely he or she is to respond effectively to second-line therapy. This is particularly true in resource-poor areas, where the number of second-line treatment options is often limited.  

Reid says he’s aware of these studies and concedes that this is a concern. One group at Cambridge University in London, however, led by Helen Lee, PhD, MSc, is actively working on two rapid point-of-care HIV viral load tests. The first, currently called SAMBA, would be used to detect HIV in newborns. This is critical, as guidelines recommend treating infants right away and the only way to know for sure whether they are actually infected is by viral load. An antibody test doesn’t work for the first year of life because the baby carries HIV-positive antibodies from its mother.

The second test could revolutionize treatment for older HIV-positive children and adults in more rural settings in Africa. The test wouldn’t help decide when to start treatment, but it would help determine when a first- or second-line treatment had stopped working. Lee says that the test will likely tell people whether their virus levels were over or under a certain number, probably somewhere between 50 or 400.

Reid hopes that the CD4 Initiative’s test could be in some people’s hands by the end of 2010. Lee doesn’t yet have a target date for her group’s test. Both, however, will make a real difference in communities devastated by the epidemic and physically out of reach of the care they need to survive.