Studies Inconclusive on Whether HIV Patients on Antiretroviral Drugs at Increased Risk of Heart Problems
Researchers are "at odds" regarding whether HIV-positive patients on antiretroviral therapy are at an increased risk for heart problems following the presentation of conflicting studies on the issue at the Ninth Conference on Retroviruses and Opportunistic Infections in Seattle, which ended yesterday, the AP/Las Vegas Sun reports (AP/Las Vegas Sun, 2/28). Antiretroviral drugs, especially protease inhibitors, have been linked to higher levels of cholesterol, triglycerides and glucose, all of which can raise the risk of vascular disease (Brown, Washington Post, 3/1). In one study, researchers from the CDC tracked 5,676 HIV-positive individuals in eight cities from 1993 to 2001. Half of the participants took protease inhibitor-containing regimens, while half took protease inhibitor-sparing regimens. Although heart attacks were "rare," 13 of the participants taking protease inhibitors suffered a heart attack, compared with two participants who did not take the protease inhibitors. The study suggested that although patients on antiretroviral therapy are at "low" risk overall for heart disease, patients taking protease inhibitors have about five times the usual risk of having a heart attack (AP/Las Vegas Sun, 2/28). However, another study that examined 37,000 patients treated with antiretroviral drugs for an average of three years at Veterans Affairs medical centers showed that hospitalizations for heart disease and stroke dropped by 10% to 20%. In addition, their death rate from all causes fell by 75%. The decline was also recorded among patients at higher risk for vascular disease, including those with existing heart problems and those over 55 years of age. "We don't think fear of vascular complications should inhibit prescribing of antiretroviral medicines," Dr. Samuel Bozzette from the VA Medical Center in San Diego said.
The Virus or the Cure?
Another study conducted among HIV-positive men enrolled in the Kaiser Permanente HMO showed similar results to the VA study. Individuals taking antiretroviral therapy, including those taking protease inhibitors, had approximately the same rates of heart attack and angina over the course of five years as individuals who did not take antiretroviral drugs (Washington Post, 3/1). HIV-positive participants, however, were nearly twice as likely to have heart disease as HIV-negative participants, and the researchers concluded that HIV itself, rather than antiretroviral treatment, might elevate the risk of heart disease (Haney, AP/South Florida Sun-Sentinel, 3/1). Another study presented at the conference supported this hypothesis. In that study, researchers surveyed 100 HIV-positive patients and found that 50% had "high-risk" levels of C-reactive protein, "a bloodstream marker of inflammation known to increase a person's risk of heart attack." The proportion of HIV-positive participants with high levels of CRP was "much greater" than the number found in the general population, the researchers reported (Washington Post, 3/1).
Additional Research Presented
Summaries of some other study findings presented at the conference appear below:
- Americans still have misconceptions about HIV transmission: Although the AIDS epidemic has been present in the United States for 20 years, nearly 50% of Americans are not knowledgeable about how HIV can be transmitted, HealthScout News reports. Statistics released by the CDC state that approximately 50% of adults surveyed wrongly said they believed HIV could be transmitted through coughing or sharing drinking glasses or public toilets. Nearly one-third of participants said that one could be infected with HIV by donating blood. The survey also found that an increasing number of people "blamed people with AIDS for causing their own illness." The survey results appear in the March issue of the American Journal of Public Health (Dotinga, HealthScout News, 2/26).
- Elizabeth Glaser Foundation awards $1.2 million to fight vertical HIV transmission: The Elizabeth Glaser Pediatric AIDS Foundation will award more than $1.2 million in new grants for its Call to Action Project, which works to prevent mother-to-child HIV transmission in the developing world. The new grants will help expand the project to several Eastern European countries and additional nations in Africa (Glaser Foundation release, 2/27). Statistics presented at the conference showed that the project is currently operational in 11 countries in sub-Saharan Africa, serves 70 clinics and hospitals and reaches 41,852 women in antenatal care. The HIV prevalence among pregnant women in the areas where the project is located is approximately 15% (Wilfert abstract, 2/27).
- Four-drug antiretroviral therapy improves viral control in advanced disease: A four-drug antiretroviral regimen that includes efavirenz produces a better virologic response than traditional triple-drug treatment, a new study finds. Dr. Margaret Fischl of the University of Miami and colleagues examined the effects of triple-drug and quadruple-drug antiretroviral therapy in 517 patients with advanced HIV infection (LaMendola, South Florida Sun-Sentinel, 2/27). The patients received a regimen consisting of either lamivudine, zidovudine and indinavir; lamivudine, zidovudine, indinavir and efavirenz; or lamivudine, zidovudine, indinavir and nelfinavir (Fischl et al. abstract, 2/26). Over two years, the four-drug regimen involving efavirenz kept viral levels under control in 77% of patients, compared to 69% in the triple-drug treatment and 52% in the four-drug therapy involving nelfinavir. Treatment side effects in the efavirenz group were comparable to those in the triple-drug group (South Florida Sun-Sentinel, 2/27). The researchers stated that the four-drug regimen involving efavirenz is an "option for advanced HIV disease" but said that the therapy involving nelfinavir resulted in inferior virologic response and a greater chance of toxicity (Fischl et al. abstract, 2/26). The four-drug regimen involving efavirenz entails taking 18 pills per day, but Fischl and colleagues are now examining a drug therapy that involves a new form of efavirenz and a new protease inhibitor, lopinavir, that would reduce the number of pills taken to four per day (South Florida Sun-Sentinel, 2/27).
- Switch to nevirapine from protease inhibitors lowers triglycerides: Patients who switch from a protease inhibitor-based regimen to a combination including nevirapine have lower levels of triglycerides than those who switch to abacavir or efavirenz, a study conducted in Spain showed. The six month study indicated that patients switching to any arm of the study had metabolic improvements (GCI Group release, 2/25).
- New treatment promising for HIV and hepatitis B co-infection: The antiretroviral drug Viread can significantly decrease levels of hepatitis B virus in patients co-infected with HIV, according to two new studies. The studies evaluated 14 patients co-infected with HIV and hepatitis B; 12 patients received treatment and two received a placebo for 24 weeks. Viread was associated with a "significant reduction" in hepatitis B viral levels during the 24 weeks of treatment and through 12 weeks in a second open-label study. Viread consists of one tablet that is taken once per day (Gilead Sciences release, 2/27).
- AIDS vaccine Remune boosts immune function among HIV-positive patients: The Immune Response Corp. announced that its AIDS vaccine candidate Remune prompted a "statistically significant increase" in CD8+ memory T cells compared to a control group in a recent study. Remune also prompted a "statistically significant improvement in the level of HIV-induced hyperactivation as evidenced by a decrease in activated T cells" among participants receiving Remune. Lead study author Dr. Eduardo Fernandez-Cruz said that the study results indicate that "therapeutic immunization may, through restoration of the patient's immune system, have a positive impact on delaying virologic failure" (Immune Response Corp. release, 2/28).
- New type of antiretroviral ready for testing: Progenics Pharmaceuticals has chosen a "humanized" form of its PRO 140 antibody for testing. PRO 140 works by blocking CCR5, a cell receptor that HIV uses to enter and infect cells. Unlike the mouse-based form of the antibody, PRO 140 is designed to be suitable for repeat dosing in humans. Progenics hopes to begin clinical testing of the drug next year (Progenics release, 2/26).
- New protease inhibitor effective among treatment-experienced patients: Tipranavir, the first non-peptidic protease inhibitor, can offer a new treatment option for patients who are experiencing treatment failure with other antiretroviral drugs, Reuters reports (Fox, Reuters, 2/26). Tipranavir, a product of drug maker Boehringer-Ingelheim, was evaluated in a study of 41 treatment-experienced patients. The study states that 85% of the participants who had experienced a decline in effectiveness for treatments with three protease inhibitors and one nucleoside reverse transcriptase inhibitor remained "fully susceptible to tipranavir" during the course of the study (Boehringer-Ingelheim release, 2/28). Only five participants developed resistance to tipranavir. Dr. Martin Markowitz, lead study author, said, "[Tipranavir] interacts in a more flexible manner with protease so it is able to bind to drug-resistant HIV. It is not as potent against wild-type virus ... but more potent against drug-resistant isolates than classic first generation protease inhibitors" (Reuters, 2/26).