As the U.S. Food and Drug Administrationweighs approval of a radical new method of AIDS prevention — a prescription pill taken once a day — advocates say the results of experimental trials in sub-Saharan Africa argue strongly for the drug’s adoption in the United States.
The pill was developed to treat people already infected with HIV. But studies published Wednesday by the New England Journal of Medicine demonstrate that it can also prevent heterosexual transmission of HIV, the most common mode of contagion in Africa.
A growing number of doctors in the U.S. are already prescribing the drug to uninfected high-risk patients as an off-label use, and some insurers are covering the considerable expense.
“It’s not officially monitored, but its use is on the rise,” said Dr. Robert M. Grant of UC San Francisco’s Gladstone Institute of Virology and Immunology, who worked on one of the new studies. “We’re already starting to see support groups for users.”
The blue tablets, which are sold under the brand name Truvada, contain a combination of two antiretroviral drugs called tenofovir and emtricitabine. Researchers began studying Truvada’s ability to prevent the spread of HIV to uninfected gay men and heterosexual men and women several years ago; the FDA has said it will make a determination on the drug’s use for HIV prevention by Sept. 14.
Publication of the Africa drug trials comes less than two weeks before the International AIDS Conference convenes inWashington, D.C.The results, as well as the FDA’s deliberations, are likely to be hot-button issues there, since both advocates and critics of using Truvada for prevention have found ammunition for their views in the studies’ findings.
Most notably, the Los Angeles-based AIDS Healthcare Foundation is vehemently opposed to the drug’s approval as a prophylaxis in the U.S. because it says the pill is dangerous, overly expensive and will detract from proven methods of AIDS prevention, such as condom use.
“Our culture is always looking for a quick fix,” said Michael Weinstein, the foundation’s president. “We want to pop a pill.... Well, there are better methods.”
In each of the three trials published Wednesday, test subjects were given Truvada or a placebo. They also received counseling on HIV risk reduction, condom use and other contraceptives. The treatment’s success was closely related to whether the subjects used the drug as intended and how strongly they perceived themselves to be at risk of infection.
The study that showed the highest rate of success involved 4,747 married couples in Kenya and Uganda. In each case, one of the spouses had HIV and the other was uninfected. Truvada reduced transmission of the virus by up to 75%, according to the report; the medication was deemed so effective that the study ended early and people on the placebo switched to the drug.
However, a related study that focused exclusively on healthy women in Kenya, South Africa and Tanzania — some married, some unmarried — was discontinued early because Truvada failed to significantly reduce infection rates. Although 95% of test subjects told researchers they were taking the pills regularly, blood tests suggested that less than 40% of the women actually did so.
“We hypothesize that the women’s perception that they were at low risk for HIV infection may have contributed to the poor adherence,” wrote the study authors, who were from the U.S., South Africa, Kenya, Britain and Belgium. Daily pill regimens may have also posed a difficulty for some of the women, though the researchers weren’t sure why.
The third study involved healthy single men and women in Botswana ages 18 to 39. Half were asked to take Truvada once a day and the other half took a placebo. Over three years, those who got the medicine were 62% less likely to become infected than those who got the dummy pill, researchers from theU.S. Centers for Disease Control and Prevention and their collaborators reported.
But the study had important limitations. Many volunteers dropped out, which prevented the researchers from determining whether the drug was protective for men and women independently, as it was in the trial involving married couples.
The report also raised questions about Truvada’s effect on bone mineral density, as the researchers observed a “small but significant decline.” Other side effects, such as nausea, vomiting and dizziness, occurred more frequently in those who took the drug instead of a placebo, but those symptoms lessened after the third month, the authors wrote. The other studies also noted side effects of gastrointestinal problems and fatigue during the first month.
The pills were supplied byGilead Sciences Inc., the Bay Area firm that makes Truvada and is seeking fast-track approval from the FDA.
For study researchers and many AIDS advocacy groups, the take-away message from the three trials was that Truvada could be an effective tool in the battle against AIDS, if used correctly.
“Adherence matters,” said Dr. Lynn Paxton, who coordinated the Botswana study at the CDC. “If you don’t take the pill, it won’t work, no matter what else you do.”
Groups like the AIDS Vaccine Advocacy Coalition and amfAR, the Foundation for AIDS Research, are citing these data as they lobby for the FDA to approve the drug and for the CDC to release guidelines on its use as soon as possible.
Last year, the CDC issued advice on using Truvada in gay men who are HIV-negative, but the agency has not yet done the same for heterosexuals. On Wednesday, CDC officials urged physicians to wait for those guidelines before prescribing the drug. However, they said that in urgent situations, doctors should follow the cautions and procedures laid out for gay men, including requirements for pre-treatment screening, dosages, periodic testing and counseling.
Truvada’s chief critics contend that the drug is prohibitively expensive in the U.S., where an annual supply can cost about $10,000. They also fear it will reduce the use of condoms.
“You have to be really paranoid about your pants falling down to wear a belt and suspenders,” Weinstein said.
But Grant, of UCSF, said the drug’s detractors were overstating the effectiveness of condoms. Although they are more likely to be used during casual relationships, their use tapers as relationships grow more intimate.
“We need to be realistic about the limits of condom use,” he said.