By Bob Huff
At the International AIDS Conference in Durban, South Africa, in 2000, when the movement to provide universal access to antiretroviral treatment for people with HIV around the world began in earnest, guidelines for the standard-of-care treatment of people with HIV were similar everywhere: begin therapy when CD4 counts fall near or below 200 and use a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor with two nucleoside RT inhibitors (NRTIs) such as stavudine and lamivudine. Subsequently, treatment guidelines have diverged. While stavudine is no longer recommended in the United States and other northern countries due to toxicity concerns, as the lowest priced antiretroviral (ARV) drug available in a generic form it remains a staple of regimens in the developing world. And though initiating therapy is now generally recommended once CD4 cell counts reach 350, this standard has been implemented in few African countries.
At the Fifth International AIDS Society (IAS) conference in Cape Town in July 2009, Daniel Fitzgerald of the Weill Cornell Medical College presented an important study demonstrating that initiating ARV treatment when CD4 counts are below 350 (but not waiting until they reach 200) reduces the incidence of tuberculosis and death. The CIPRA HT 001 study randomized 816 patients in Haiti to either begin ARV treatment at a CD4 cell count of 350 cells/mm3 or to defer treatment until the CD4 count approached 200 cells/mm3 or when symptoms of AIDS appeared. There were 23 deaths and 38 cases of TB in the group that put off starting treatment compared with only 6 deaths and 18 cases of TB in the group that started earlier. The results were statistically significant.1 This study is especially important for understanding how to prevent death from TB, the biggest killer of people with HIV in the developing world and a disease that can be deadly at CD4 counts above the treatment threshold of 200 set for the prevention opportunistic infections associated with AIDS.
These results illuminate the gaps in current practices and the commitment of resources required to make universal treatment a reality. Reuben Granich, of the World Health Organization, presented a sobering look at the challenges but made a strong case for why investing in ARV access will be essential for ultimately controlling HIV.2 In 2007, only 31% of people eligible for ARV treatment (those with a CD4 count under 200) were on therapy, with resource commitments falling short by about half of the need. As treatment guidelines change to recommend therapy earlier in the course of the disease, the access gap will be magnified. And it is likely that existing and emerging evidence will convince many that to prevent TB and other non-AIDS events, starting even sooner is better. But Granich is mainly concerned with the population benefits of suppressing HIV replication with drugs, and at the Cape Town conference he presented a theoretical model that suggests that the HIV epidemic could be tamed by universal testing and treatment for all with the virus, regardless of CD4 count. Control of the epidemic would come from reducing the spread of new infections by reducing the number of people who are infectious. This theory is based on observations that people with very low viral load levels have a much smaller chance of infecting others. If nearly everyone with HIV is on treatment, according to the model, the virus should virtually cease to circulate in the population.
While the costs and logistics of implementing universal testing and treatment are massive, Granich’s model suggests that the effort would become cost-effective by 2030 as the epidemic comes under control. But what’s most convincing about the model are the projections of the human and monetary cost of continuing on the current course of treating only those whose CD4 counts have declined. Anything less than universal testing and immediate treatment will allow the number of people with HIV to continue to grow, with no end to the epidemic in sight.
1. Fitzgerald D, et al. When to start ART in developing countries. Program and abstracts of the Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, July 19–22, 2009, Cape Town, South Africa. Abstract WESY201.
2. Granich R. HAART as prevention. Program and abstracts of the Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, July 19–22, 2009, Cape Town, South Africa. Abstract MOPL101. Available online at http://www.ias2009.org/PAGMaterial/MOPL101_Granich_1.ppt.