SAN FRANCISCOA clinical trial reported at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) suggests that people infected with HIV who are taking complicated protease-inhibitor-containing regimens to suppress the virus may be able to safely switch to a simplified maintenance regimen requiring only two pills twice a day.
Current regimens of highly active antiretroviral therapy (HAART), which include a protease inhibitor and two other anti-HIV agents, require patients to take large numbers of pills daily (up to 20 in some regimens). Furthermore, use of protease inhibitors has been associated with adverse events such as hyperlipidemia. These difficulties with HAART often lead to patient noncompliance with therapy.
The studys objectives were to see if a switch to simplified therapy leads to comparable virological suppression and to compare CD4 rates and lipid abnormalities, said M. Opravil, MD, of the Division of Infectious Diseases, University Hospital, Zurich, Switzerland.
All patients in this randomized study previously had been treated with more than 6 months of HAART containing protease inhibitors; had shown HIV suppression for more than 6 months (fewer than 50 copies/mL of HIV-1 RNA); and had no prior virologic failure while taking the nucleoside analog reverse transcriptase inhibitors zidovudine(Drug information on zidovudine) (Retrovir, AZT) and lamivudine(Drug information on lamivudine) (Epivir, 3TC).
Simplified maintenance therapy included the nucleoside analog abacavir(Drug information on abacavir) (Ziagen), 300 mg twice daily, plus the combination tablet Combivir (150 mg of 3TC plus 300 mg of AZT) twice daily. Control patients in the study continued their protease-inhibitor-containing regimen. HIV-1 RNA was measured every 4 weeks.
Evaluation after 12 weeks of 153 patients (74 who continued protease inhibitors and 79 switched to the simplified therapy) found no appreciable differ-ences in CD4 or CD8 counts between the two patient groups.
Virologic failures (defined as two consecutive plasma HIV-1 RNA levels greater than 400 copies/mL) also were similar two failures, at week 25 and 26, for the continuation arm, and three failures, at week 4, 8, and 16, for the simplified therapy arm. Dr. Opravil noted that the failures tended to occur somewhat faster with simplified therapy.
A significant decrease in cholesterol levels with an increase in high-density lipoprotein (HDL) values was seen in the patients on the simplified therapy, Dr. Opravil said.
Longer Follow-up Needed
It is too early to state that simplified therapy has the same potency as regimens containing a protease inhibitor, Dr. Opravil said in an interview with Oncology News International. But there are indications that lipid abnormalities stemming from protease inhibitors may be reversed when therapy is switched, which could result in a lower risk of cardiovascular disease. We need a longer follow-up time.