PrEP using Tenofovir plus Emtricitabine May Offer Benefits even if HIV Infection Occurs

Animal studies of pre-exposure prophylaxis (PrEP) using tenofovir (Viread), with or without emtricitabine (Emtriva), have produced promising results, and large clinical trials in humans are currently underway. Prevention strategies using antiretroviral drugs are unlikely to be 100% effective, due to variations in efficacy, adherence, and other factors. But there is growing evidence that PrEP may have benefits even for individuals who become infected.

In the October 2008 Journal of Acquired Immune Deficiency Syndromes, clinicians at the Aaron Diamond AIDS Research Center (ADARC) in New York City described the case of a 38-year-old HIV negative gay man who intermittently used tenofovir plus emtricitabine (the Truvada fixed-dose combination pill) before or after engaging in unprotected anal intercourse.

The man reported having unprotected anal sex on several occasions with multiple partners between September and November 2006. In effect, though he was given Truvada as post-exposure prophylaxis (PEP) for prior sex acts, it also served as PrEP for subsequent ones. However, he also had unprotected sex during periods when he was not taking Truvada.

The patient repeatedly tested HIV negative, but eventually tested positive in December 2006, despite taking the drugs. But he experienced a slow seroconversion, and it is not clear when he actually became infected.

The man had a strong immune response to the virus, resulting in a very low viral load (below 1000 copies/mL) and a consistently high CD4 cell count and CD4 percentage without treatment. He had no symptoms of acute infection and did not experience the large decline in CD4 cells in the gastrointestinal tract mucosa that often occurs soon after infection. Furthermore, genetic testing showed that he did not carry mutations associated with long-term non-progression or "elite controller" status, including CCR5-delta32.

"We suggest that even if prophylactic antiviral treatment failed in preventing infection, it may have dramatically reduced levels of viral replication postinfection, avoiding the extensive CD4 cell depletion that usually accompanies acute infection and possibly enabling an adequate immune response to develop and partially control the infection after the withdrawal of the drug," the authors wrote.

"Despite the failure of [tenofovir/emtricitabine] as prophylaxis, selection for drug-resistant transmission did not occur and the blunting of postinfection levels of viremia likely reduced the probability of subsequent forward transmissions during the acute phase," they continued. "These results support continued investigations of the use of antiretrovirals as a means to reduce HIV-1 transmission."

This case report supports recent findings "Tenofovir (Viread) Administered Orally, by Injection, or as a Rectal Microbicide Protects Monkeys from Infection with HIV-related Virus" that monkeys who became infected with a simian variant of HIV despite receiving tenofovir and emtricitabine (oral, injected, or as a microbicide gel) had lower viral loads.

10/07/08

Reference

N Prada, B Davis, P Jean-Pierre, and others. Drug-susceptible HIV-1 infection despite intermittent fixed-dose combination tenofovir/emtricitabine as prophylaxis is associated with low-level viremia, delayed seroconversion, and an attenuated clinical course. Journal of Acquired Immune Deficiency Syndromes 49(2): 117-122. October 2008. (Abstract).