HIV Salvage Therapy and Resistance Testing
This report was reviewed for medical and scientific accuracy by Mark B. Feinberg, MD, PhD , Associate Professor of Medicine and Microbiology and Immunology, Emory University School of Medicine; Attending Physician, HIV/AIDS Service, Grady Memorial Hospital, Atlanta, Georgia.
Physicians currently treat human immunodeficiency virus (HIV) with multiple-drug therapy known as highly active antiretroviral therapy (HAART). Research presented at the Infectious Diseases Society of America (IDSA) validated the success of HAART in the prevention of complications and related AIDS deaths, but also confirmed that many patients find it impossible to adhere to the complex regimens associated with HAART. Other studies reported success with simplified versions of HAART.
The advent of HAART raised the hopes of many patients in terms of the successful management of HIV infection, since the regimen effectively suppresses the virus over the long-term and often prevents HIV from developing into symptomatic AIDS. But the multiple drugs in the HAART regimen must be taken precisely as prescribed, without fail, which has led to concerns that the complexity of this treatment hinders patients' adherence. Observers believe that large numbers of pills, frequent dosing, drug interactions, and drug side effects lead to non-compliance. By understanding the problems that patients have with these regimens-and developing simpler drug combinations-researchers hope to enhance treatment success.
Jolynn M. Pratt, MD, and colleagues from the University of Michigan School of Medicine, Ann Arbor, studied 2,025 people diagnosed with AIDS. They divided the patients into two groups based on why they were diagnosed with AIDS-whether by the occurrence of an opportunistic infection or the presence of AIDS-defining laboratory indicators of AIDS-and evaluated survival based on whether they received HAART.
The study found that patients who received HAART lived much longer than patients who did not. Patients who did not receive HAART lived an average of 10.2 months after presenting with an opportunistic illness-such as pneumonia or a fungal infection-or 21.6 months after being diagnosed with AIDS on the basis of laboratory findings. With HAART, however, persons with opportunistic illness lived a median of 95.4 months, and those with laboratory indicators lived 80.8 months.
Other researchers at the Centers for Disease Control and Prevention (CDC) and Northwestern University Medical School confirmed that most patients with HIV do, indeed, receive HAART and that HAART reduces HIV viral load, AIDS-related complications, and deaths. It also increases CD4 cell counts among persons with HIV. They drew these conclusions after evaluating 5,006 patients seen in private and public HIV clinics from 1994 to 1999. During this time, HAART usage rose dramatically-from 3.6 percent in 1995 to 88 percent in 1999.
Frank J. Palella, MD, and colleagues reported that death rates fell from 30 per 100 persons per year to two per 100 persons per year in patients followed for an average of 19.8 months. In addition, opportunistic infections decreased by over 85 percent.
The study also found that patients receive increasingly complex HAART regimens-including numerous drugs from different drug classes-as they progress from initial diagnosis to more serious illness.
Adherence Problematic for Some Types of Patients
Several reports at this meeting confirmed that adherence to these complex regimens is difficult for many patients.
William J. Burman, MD, Denver (Colorado) Board of Public Health, reported the results of a survey of 100 patients attending an urban HIV clinic. The survey asked patients about their compliance with their prescribed drug regimens and their reasons for not taking their medications and compared their responses with pharmacy records.
"Nonadherence [to] antiretroviral therapy in an unselected clinic population was relatively common. Self-reported adherence did not correlate well with pharmacy adherence," he said.
Almost three-quarters of patients claimed to take their medications as directed, but pharmacy records revealed that just over half of these patients had adequately filled their prescriptions. Several factors were related to lack of compliance, including alcohol abuse, life stresses, Hispanic or African American race or ethnicity, and history of intravenous (IV) drug use. The most commonly cited reasons for missing doses were being busy, forgetting, not feeling like taking the medications, and experiencing side effects. Patients said that having written instructions, medication boxes, and fewer drugs to take would aid compliance.
Johns Hopkins University researchers also found inadequate adherence to antiretroviral drugs, especially among women and active IV drug users. Outside social stresses-such as running out of money and eating fewer than two meals a day-were important reasons behind patients' failures to take their medications, according to self-reports from patients in an urban HIV clinic.
Once-Daily Combination Therapy
A once-daily, multiple-drug, antiretroviral regimen suppressed the HIV virus for as long as 48 weeks in a study presented by French investigators. The study included 40 previously untreated HIV-positive patients who received a new drug regimen that included emtricitabine (Coviracil®)-an investigational nucleoside reverse transcriptase inhibitor-along with didanosine (Videx®) and efavirenz (Sustiva®). The triple therapy was safe, with potent antiviral immunologic effects lasting the entire 48-week study period.
After 48 weeks, 95 percent of patients continued to maintain plasma HIV-1 RNA below 400 copies/mL, and CD4 cell counts increased by a median of 209-both indicators of a good treatment response.
Jean-Michel Molina, MD, Principal Investigator, Department of Infectious Diseases, Saint-Louis Hospital, Paris, France, noted that patients were very cooperative with the regimen. Of the 40 patients, none failed to receive their medications or were lost to follow-up. Only four patients discontinued the study before week 48 because of side effects, virological failure (treatment response not maintained), or personal choice. Side effects were fairly mild and occurred early in the study, then subsided. These patients have been on the medication for about a year and a half and are still doing well, he added.
Dr. Molina believes that once-daily therapy has been advantageous in keeping the patients compliant with the medication regimen, though they still have to take five pills.
"We can't conclude that compliance with once-daily therapy is better than with standard treatment. But when you compare the results to those of other clinical trials, they look very good," he said. French researchers initiated a large trial in June involving 400 patients to compare this once-daily triple regimen with other triple HAART combinations, he concluded.