Truvada this week became the first drug approved by the U.S. Food and Drug Administration (FDA) for the prevention of HIV infection and AIDS in individuals at "high risk."

The FDA evaluation relied heavily on two large studies. One was a UCSF-led study of men and transgender women who have sex with men, which found that Truvada reduced risk of infection by 42 percent. The second, Partners PrEP, was a study in Africa of HIV transmission in heterosexual couples. Researchers found that risk was reduced by 75 percent.

Apart from the specific populations studied in these large-scale trials, others deemed to be at high risk also can lower their chances of becoming infected. For instance, Deborah Cohan, MD, MPH, a UCSF obstetrician and gynecologist who specializes in the care of pregnant women with HIV, has been evaluating the use of Truvada in pregnant women in the U.S. who are uninfected, but whose male partners have HIV.

Deborah Cohan, MD

"There is a growing body of evidence to suggest that pregnancy increases the risk of HIV acquisition," she said.

Additional large studies, including FEM-PrEP and TDF2, also have shed light on Truvada use in women. "The data that support its use for women are for resource-limited settings outside the U.S.," Cohan said. "One of the things that was clear ... is that adherence to the treatment is key, and that perception of risk probably drives adherence."

Testing Pre-Exposure Prophylaxis (PrEP)

Cohan is expanding this research, creating a multi-center collaborative project to study the treatment approach, called pre-exposure prophylaxis (PrEP), in uninfected women who intend to become pregnant. Cohan runs the UCSF Perinatal HIV Clinic as part of the Women's HIV Program at UCSF and is medical director of the Bay Area Perinatal AIDS Center (BAPAC) at San Francisco General Hospital and Trauma Center.

"Now that there is FDA approval we want to try to identify optimal candidates for this intervention, and to understand how to optimize adherence to prescribed therapy," she said. "This includes understanding peoples' perception of risk," she said.

An individual's risk of infection - and how much taking a daily Truvada pill may reduce it - depends on several factors, such as the precautions sexual partners already may be taking.

Research has made it clear that, when HIV-infected individuals lower levels of virus in their blood by taking antiretroviral therapy, they not only prevent progression of HIV-associated disease, they also greatly reduce the risk of transmitting the virus to their sexual partners.

Among heterosexual couples, if HIV levels in the HIV-positive partner remain suppressed with antiviral therapy, the risk of HIV transmission to the uninfected partner appears to be especially small, Cohan said. "It's officially not zero, because we know of at least one case report," she said.

In addition, condom use is effective in preventing the spread of HIV, and avoiding the sharing of needles is an effective strategy for preventing the spread of HIV that stems from injection drug use.

Of course, couples trying to conceive do not use condoms, and keeping viral loads low in HIV-infected individuals requires reliable adherence to antiretroviral therapy, Cohan said. The U.S. Centers for Disease Control and Prevention last year estimated that barely one-in-four HIV-infected individuals in the U.S. has achieved viral suppression, which the agency defined as the presence in the blood of 200 or fewer copies of the virus per milliliter.

HIV-Negative Partner May Gain Control to Remain Uninfected

"Just relying on HIV-positive partners taking their medications and being virally suppressed does not guarantee that they're not going to transmit HIV to their HIV-negative partners," Cohan said.

"What we do for pregnant women who are on PrEP is to try to get their male partners onto antiretrovirals if they are not yet on them," she said. "We ask that their partners' providers obtain monthly measures of viral loads to make sure they are suppressed. That's not standard practice. Usually people may get viral loads every three months, or even less often if they have been suppressed for a while.

"I think that this gives control to the negative partner to keep herself HIV-negative," Cohan said.

When blood tests indicate that one partner is HIV-positive and the other is HIV-negative, the couple may be described as "serodiscordant."

"Many of the women I know who are in serodiscordant relationships are in excellent communication with their partners, and their partners' providers are in excellent communication with us," Cohan said.

"But probably more frequently the woman doesn't necessarily know whether her partner is taking antiretrovirals regularly, or how often he is having viral loads checked. In many cases his HIV provider may not even know that he is sexually active with an HIV-negative woman."

Who Will Prescribe Truvada?

Sorting out how individuals who can lower their infection risk with PrEP will be able to pay for Truvada is one question on the minds of many, but there are additional issues when it comes to getting Truvada into the hands of patients, Cohan said.

"Many HIV clinics are not set up to take care of HIV-negative individuals," Cohan said. "They may be reimbursed for the numbers of encounters that they have with HIV-positive patients. Many of them are not prepared to care for and to be reimbursed for caring for HIV-negative people.

"On the flip side, most OBGYN clinics and most general practice clinics that don't provide HIV care, per se, don't feel equipped to prescribe Truvada for HIV-negative women in serodiscordant relationships.

"From my standpoint it's relatively straightforward - there are going to be protocols established," Cohan said. "Still, it's unfamiliar. At most places they are not comfortable prescribing antiretrovirals if it's not an HIV clinic."

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