Plotting the Course

In the era of HAART, management of HIV continues to evolve for both treatment-naïve (those new to treatment) and treatment experienced (those who have had treatment) individuals. Currently, more than 20 approved antiretroviral agents from four different drug classes are available:

• nucleoside/nucleotide reverse transcriptase inhibitors,
• non-nucleoside reverse transcriptase inhibitors,
• protease inhibitors, and
• A fusion inhibitor.

When used in combination, these drugs can suppress HIV replication, restoring and maintaining immune function.

Over the last decade, HAART regimens have become less toxic, less complex and, therefore, more accessible to people living with HIV/AIDS. Agents active against drug-resistant virus have become available, offering hope to people in whom drug-resistant HIV has developed, and tools such as viral load testing and genotype and phenotypic resistance assays have accompanied these therapeutic improvements. But all is not smooth sailing.

HAART is no more a cure than it ever was. Its adherence requirements, although now easier to meet, are still extremely taxing. They last not for a week, or a month, but forever.

Moreover, the survival benefits of HAART are still accompanied by side effects and toxicities. Sometimes, they can be serious. Cardiovascular disease, abnormal elevations in lipid levels, insulin resistance, and bone loss are just some of the long-term complications that may be associated with antiretroviral therapy. A growing body of data addresses causative factors and management strategies, which range from lifestyle changes to pharmacological interventions to switching antiretroviral agents.

Setting Sail

In April 1998, the U.S. Public Health Service issued the first comprehensive, evidence-based HIV treatment guidelines to address crucial questions, such as when to start HIV treatment, which agents to start with, which to avoid, and what shortcomings exist for antiretroviral therapy. Clinical guidelines are updated regularly to reflect research results on management and treatment of HIV disease. Most recently, Guidelines for the Use of Antiretroviral Therapy in HIV-1 Infected Adults and Adolescents was released in May 2006.

The original guidelines suggested an aggressive “hit early and hit hard” strategy for treating HIV disease, based on the belief that it was possible to eradicate HIV with HAART. It was subsequently demonstrated that complete eradication of HIV is not possible with current therapies, even among persons with no detectable virus in their bloodstream. This discovery was coupled with increasing reports of body shape changes, elevated lipid levels and other toxicities, and drug resistance in persons unable to maintain near-perfect adherence—not just to one drug but to a whole class of drugs. Given available data related to the relative risk for progression to AIDS and the potential risk and benefits associated with initiating therapy, most specialists in this area believe that the evidence supports initiating therapy in asymptomatic HIV-infected persons with CD4⁺ T cell counts of 200-350 cells/mm³.

Into the Horizon

Innovations in therapy continue to modify how treatments are administered and what those treatments are. Mutations of the HIV virus that confer resistance to a single agent or an entire class of drugs have made drug resistance a central issue in HIV therapy. This development has made resistance testing a crucial clinical tool for optimizing anti-HIV therapy.

Resistance testing results are an important tool for patients and clinicians in making treatment decisions, particularly for treatment-experienced patients. Preliminary data suggest that initiation of therapy with a drug to which the patient’s virus is resistant may result in suboptimal viral suppression. Using genotypic testing to guide selection of initial therapy appears to be cost-effective. Genotypic testing identifies actual mutations associated with drug resistance, and phenotypic testing measures sensitivity to a specific drug.

In addition to tools like resistance testing, several promising new drugs from established and novel classes are in the pipeline. New drug classes hinder HIV’s entry into CD4⁺ T cells (entry inhibitors), obstruct HIV’s integration into cellular DNA (integrase inhibitors), and interfere with the final stages of HIV’s assembly and exiting process (maturation inhibitors). In the future, these developments and others like pharmogenetics may offer increasingly efficacious treatment prospects for people living with HIV/AIDS.

Many people depend on State ADAPs for access to HAART and other treatments for HIV/AIDS and its associated conditions. In the single month of June 2005, for example, ADAPs provided medications to 96,404 people, according to the National ADAP Monitoring Project, a collaborative activity of the National Alliance of State and Territorial AIDS Directors (www.nastad.org) and the Henry J. Kaiser Family Foundation (www.kff.org). Like all CARE Act programs, ADAPs reach people who have poor access to health care: in June 2005, 62 percent of individuals receiving treatments through ADAPs were minorities, 73 percent were uninsured, and 49 percent had CD4+ T cell counts of <350 at the time of their enrollment in the program. Without ADAPs, access to health restoring and life improving drugs would be precarious, at best, for these individuals.

HAART has been a principal driver of increased demand for ADAP-funded treatments over the last decade. Increased appropriations to the program have reflected that demand. However, the Federal appropriation to ADAPs (see Figure 13) is just one variable in the access-to-treatments equation. Other factors include costs of medications, State ADAP formularies, and ever-increasing HIV/AIDS prevalence. In some States, these variables spell waiting lists for ADAP enrollment, limited access to particular drugs—and poorer health and quality of life for people who have nowhere else to turn.