There are now 19 antiretroviral drugs approved by the Food and Drug Administration for the treatment of HIV infection that can have potentially serious side effects and interactions with other drugs.6,7 Decisions about when to start HAART, when to change therapy, and which drugs to prescribe have become increasingly complicated. Safe and effective use ofHAART in North America requires measurements of plasma viral load and CD4+ T lymphocytes, as well as monitoring for viral resistance and adverse drug reactions. The increasing complexity of the care of HIV-infected persons is reflected in the frequent updating of clinical care guidelines.6,7 In the United States, it has been shown that the survival of patients is dependent upon the experience oftheir physicians in treating HIV-infected persons,8 and that experience should inform the current discussions about providing access to antiretroviral drugs to developing countries. The introduction of HIV-treatment programs in those countries offers the opportunity to increase the number of providers with access to the training and information required for the safe and effective use of HAART.Infrastructure Requirements for the Use of HAART
As noted above, current North American and European clinical care guidelines incorporate measurements of plasma HIV load and CD4+ T lymphocytes and testing for viral resistance as essential tools for the rational, effective use of HAART.6,7 Countries with limited resources lack the laboratory infrastructure and trained technicians to perform theseassays. Complete blood counts, liver-function tests, and serum creatinine and lipid levels are routinely used in assessing patients for adverse drug reactions. Efforts to expand access to HAART should be accompanied by a more evidence-based approach to optimize HIV care guidelines for local settings. This approach will require adequate laboratory and clinical infrastructure to collect the evidence.Alternative, low-cost methods for monitoring patients receiving HAART are a public health priority. In addition, the predictive value of lower-cost clinical end points, such as those recently used in Haiti, needs to be evaluated.9
There is increasing evidence that resistant strains of HIV are being transmitted in North America and Europe as a result of the difficulty ofcompletely suppressing viral replication.10,11,12 The World Health Organization (WHO) has responded to this concern by establishing the Global HIV Drug Resistance Surveillance Network to assist countries in monitoring for the emergence of HIV drug resistance.13 Antiretroviral agents must be introduced in a way that ensures a sustainable drug supply in order to avoid the early pitfalls seen in theIvory Coast and Gabon, where erratic therapy resulted in high levels of drug resistance.14,15 Apart from early treatment failure, resistant strains of HIV may rapidly abrogate the effectiveness of zidovudine, lamivudine, and nevirapine for the prevention of vertical transmission of HIV; this is currently among the most important global HIV interventions.
Improving Treatment Guidelines
Currentguidelines from the Department of Health and Human Services, the British HIV Association, and the International AIDS Society recommend the initiation of HAART in asymptomatic HIV-infected patients with CD4+ T-lymphocyte counts of less than 200 cells per cubic millimeter (with treatment considered in patients whose counts are between 200 and 350 cells per cubic millimeter).6,7,16 Recent WHOguidelines have also adopted this CD4+ T-lymphocyte level for the initiation of HAART in asymptomatic patients in developing countries.13 The HAART guidelines were based on data from clinical trials in North America, Europe, and Australia and may not take into account genetic and geographic differences in the normal range of CD4+ T-lymphocyte levels in other countries.17,18 A potential limitation of...