Project 170581

Highly active antiretroviral therapy (HAART) has drastically reduced the morbidity and mortality associated with HIV infection, and transformed HIV from an invariably fatal disease into a manageable, chronic condition. However, the inconvenience, high cost, potential side effects, and significant risk of developing drug-resistant HIV associated with taking daily, lifelong HAART make the potential delay of HAART initiation an extremely desirable goal for HIV-infected individuals. Suppression of herpes simplex virus (HSV)-2 co-infection may provide a novel therapeutic strategy for achieving this goal. HSV-2 is among the most common co-infections seen in persons infected with HIV, with rates of up to 52-95%. This co-infection is associated with increased blood levels of HIV, a major predictor of HIV disease progression, even when the person has no herpes symptoms. Medications such as valacyclovir that suppress herpes can also decrease blood levels of HIV, but the potential long-term clinical benefits of this drug have not been adequately studied. It is thus hypothesized that valacyclovir could slow HIV disease progression and prolong the period of time before a co-infected person needs to initiate HAART. This research has been designed to answer this important question through a randomized, placebo-controlled, multi-centre clinical trial. The study will enroll 480 HIV, HSV-2 co-infected individuals over two years from clinics participating in the Canadian HIV Trials Network (CTN) and from the HIV/AIDS Clinical Research Centre of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Each participant will be randomly assigned to either valacyclovir or an identical-appearing placebo twice daily, and will be followed up with routine medical assessments and blood tests over 3 additional years. The primary goal is to determine whether patients using valacyclovir can delay initiation of HAART by at least 9 months, compared to those taking placebo.

evaluating antiviral therapy for delaying initiation of HIV treatment in co-infected patients