The newspaper headlines couldn't paint a more promising picture: "Drug Combo Promising in Combating HIV" (San Jose Mercury News), "Pill to Prevent AIDS Shows Promise" (Toronto Star), "AIDS Drugs Show Promise at Prevention" (Houston Chronicle).
The front-page news comes from a study conducted by the U.S. Centers for Disease Control (CDC) involving monkeys that were able to ward off a modified version of HIV (SHIV) after receiving a combination of tenofovir (Viread®) and emtricitabine (Emtriva®) as pre-exposure prophylaxis (PREP). PREP is one of several prevention interventions – which also includes vaginal and rectal microbicides, as well as vaccines – that may minimize the risk of HIV in people at high risk for the infection.
Optimistic headlines aside, the CDC study raises many more questions than answers.
Results from the study were first reported at the 13th Conference on Retroviruses and Opportunistic Infections (CROI), held in Denver in early February (see our story dated 2/6/06). A CDC team headed by Dr. Walid Heneine gave daily injections of tenofovir (22mg per kilogram of body weight) and emtricitabine (20mg per kilogram of body weight) to six rhesus macaques for a total of nine days. Another six rhesus macaques were involved in the study, but did not receive tenofovir/emtricitabine injections.
Nine days after the daily PREP injections began, the 12 monkeys were rectally exposed to fluid containing high concentrations of SHIV. The monkeys were exposed to SHIV once a week for a total of 14 weeks.
Among the macaques not receiving tenofovir/emtricitabine, five of the six were infected with SHIV after 14 weeks. Among the six macaques that received tenofovir/emtricitabine PREP, none were infected with SHIV after 14 weeks of virus exposure.
These results, Dr. Heneine stressed, are certainly more encouraging than those reported at the 12th CROI held in 2005, in which four out of four monkeys given tenofovir alone were infected after weeks of SHIV exposure.
Without doubt, the recent CDC data are incredibly optimistic and have paved the way for dual-drug PREP studies involving volunteers, including one slated to begin in Africa. At the Denver CROI gathering, however, Dr. Heneine's commentary on the study was more cautious than what appears in current media reports.
For starters, the tenofovir and emtricitabine used in the study were injectable fluid versions of the drugs. These versions are not necessarily the same as the commercially available oral tablet versions of the drugs, usually taken together as Truvada®. While the emtricitabine dose used in the study yielded blood concentrations similar to those seen in humans, the injected dose of tenofovir resulted in blood concentrations that are higher than those seen in humans receiving oral tenofovir.
Another potential concern is the emergence of drug-resistant virus. If PREP using tenofovir and emtricitabine is not effective – meaning that HIV infection occurs while on the drugs – will the virus quickly mutate, preventing the use of these and other HIV medications for treatment? Additional studies involving animals and humans are necessary to answer this important question.
Finally, there have been some community concerns that the proven effectiveness and availability of PREP will result in increased risk taking. According to a press release generated by several prominent HIV/AIDS advocacy organizations – the Community HIV/AIDS Mobilization Project (CHAMP), Gay Men's Health Crisis (GMHC), the AIDS Vaccine Advocacy Coalition (AVAC), and the Treatment Action Group (TAG) – the issue of increased risk taking should be taken into consideration, but should not slow ongoing research. "The risk of behavioral disinhibition cannot be discounted, and must be studied." Such concerns "should not deter research, and in fact, give further urgency to the need to answer the question: Does PREP work, using tenofovir, other drugs, or drug combinations?"
Sources:
Garcia-Lerma J, Otten R, Qari S, et al. Prevention of rectal SHIV transmission in macaques by tenofovir/FTC combination [Abstract 32LB]. 13th Conference on Retroviruses and Opportunistic Infections, Denver, 2006.
Community HIV/AIDS Mobilization Project (CHAMP)
