Rationale and Strategies for Treatment Interruption

“the advent of highly active antiretroviral therapy in the mid 1990s resulted in a dramatic increase in survival of hiv patients, especially among those with advanced disease,” Dr. Wafaa El-Sadr said in beginning her February 2006 prn lecture. Follow-up studies, she explained, demonstrated the durability of this effect, with decreasing hivassociated morbidity and mortality during the late 1990s and early 2000s. She also acknowledged, however, that while combination antiretroviral treatment has changed the face of the hiv epidemic and enabled physicians to provide truly effective therapy, several issues and limitations of these regimens have emerged. The most significant limitation has been the necessity and challenge of continued daily adherence to the medications. “Taking these medications day in, day out is difficult for patients,” she said. The frequently cited multicenter study of antiretroviral adherence, conducted by Dr. Sharon Mannheimer and her colleagues, demonstrated rapid waning of adherence with only 60% of patients reporting 100% adherence eight months after initiation of therapy (Mannheimer, 2002). Extrapolating these data implies worsening of adherence over years of therapy, resulting in drug resistance and resultant loss of treatment options. Metabolic effects are another concern with hiv treatment. More alarming is evidence of increased myocardial infarction rates among patients on antiretroviral therapy. An important study on this subject is the dad study (Data Collection on Adverse Events of Anti-hiv Drugs), which found an increased risk of coronary artery disease in people on all types of antiretroviral therapy (Law, 2003). Additional metabolic and general side effects of antiretroviral therapy include cardiovascular complications, lipoatrophy, peripheral neuropathy, and accelerated liver disease (Julg, 2006). The occurrence of severe therapy-related adverse events has gained prominence in the era of combination antiretroviral therapy. In a crossprotocol study, rates of grade 4 adverse events associated with antiretroviral treatment were shown to be higher than those of aids events or deaths (Reisler, 2003). “While we see a dramatic decrease in the development of aids as well as associated deaths, there has been an increase in the development of adverse events of a variety of organ systems,” noted Dr. El-Sadr. The high cost of medications also continues to be an issue. Although programs exist in New York State and New York City for financial support for treatment, many parts of the United States and most other parts of the world do not have such programs established. The continued inability to eradicate or cure hiv gives the prospect of lifelong drug treatment enormous monetary implications.