Although ADAPs have been consistently plagued by funding resource constraints, program directors and staff have worked tirelessly to stretch dollars through coordinating with Medicaid programs, tapping into State high-risk insurance pools to purchase health insurance, obtaining rebates from pharmaceutical companies, and using a pharmacy benefits manager to buy and distribute drugs. With growing constraints on State resources, many ADAPs have had to institute cost-cutting measures, such as lowering financial eligibility, reducing the formulary (although they are required to include at least one drug from each class of antiretrovirals), capping enrollment, or instituting waiting lists.38,39,40
Side Effects, Drug Toxicity, and Resistance
Jubilation about HAART began to fade as reports of new side effects, drug toxicity, and drug failure emerged. Reports describing a cluster of metabolic and body shape changes—visible fat loss in the face, limbs, abdomen and buttocks; abnormal fat accumulation in the breasts, abdominal area, and on the back at the base of the neck (“buffalo hump”); elevated lipid levels; and insulin resistance (prediabetes)—in people taking HIV PI-based therapy began to appear.41,42 “In the mid- to late 1990s, it was hard to put patients that weren’t really sick on the drugs we had. People had horrible side effects from taking drugs that made feel worse than they did before,” explains Travieso Palow.
The body shape changes had a terrible effect on quality of life; many people felt disfigured by visible signs of HIV infection, and that led to isolation and depression and, in some cases, discontinuation of ART.43,44,45,46,47 “I can remember many times we had weekly provider meetings to discuss cases,” says Cheever. “Two years later, no one could believe what we decided to do, because the standard of care changed so rapidly from the early HAART era, when we didn’t even know about toxicities.”
Doctors review a patient's chart to check on recent HIV RNA lab results.
Researchers struggled to discover the cause of metabolic abnormalities and how best to treat them. Eventually, it became clear that certain NRTIs, especially stavudine and AZT, were linked to lipoatrophy.48,49 Strategies such as using insulin sensitizers, performing facial reconstructive surgery, and switching antiretroviral agents have been studied, and experts now recommend avoiding stavudine and AZT when other options exist.47
In contrast, getting to the cause of and finding treatment for fat accumulation has been more complex. A constellation of risk factors has been identified, such as older age, higher body mass index, lower CD4 cell nadir, and White race.50 Several approaches have been studied (e.g., changing antiretroviral agents, diet and exercise, metformin, therapy with testosterone and human growth hormone), and the most effective intervention seems to be treatment with growth hormone analogs.47,51,52,53,54
Researchers discovered that HIV itself increases the risk for cardiovascular disease, along with certain antiretroviral agents and traditional risk factors.55,56 Using certain lipid-lowering agents unlikely to cause significant drug–drug interactions with antiretroviral agents, switching to lipid-friendly regiments, and changing lifestyle (e.g., smoking cessation, aerobic exercise, dietary changes) are recommended to manage lipid abnormalities and to reduce the risk for cardiovascular events.57,58 All of these approaches are used by Ryan White providers.