COMBINATION THERAPIES AGAINST HIV-1 INFECTION - EXPLORING THE CONCEPTOF COMBINING ANTIRETROVIRAL DRUG TREATMENTS WITH HIV-1 IMMUNE-BASED THERAPIES IN ASYMPTOMATIC INDIVIDUALS

The deleterious effect of HIV on the immune system begins at the time of infection. At seroconversion the virologic and immunologic factors that ultimately will dictate the rate of disease progression are belie ved to be already in place. The concept developed in this paper implie s that, to impact significantly on the progression of disease, anti-HI V therapies should be initiated as early as possible in asymptomatic i ndividuals. Published results have shown that combination drug therapi es are potent in reducing HIV-1 RNA load in plasma in asymptomatic ind ividuals, and that some HIV-1 immune-based therapies have a positive i mpact on immunological markers of disease progression, including HIV-1 cell-mediated immunity (CMI) and CD4 percent. The strategy discussed is to test a combination of antiretroviral therapy with HIV-1 immune-b ased therapy, such as the inactivated HIV-1 Immunogen preparation, in asymptomatic individuals. The goal of this combination approach is to overcome the limitations of each therapy alone. Preliminary data sugge st that antiretroviral therapy and the HIV-1 Immunogen can be combined with no noticeable interference and/or added toxicity in a broad rang e of HIV-1-infected individuals.(1) Combining both therapies may enhan ce and expand the impact on key surrogate markers of disease progressi on, although they likely achieve this impact through different mechani sms. Thus, the primary question remains: Can these effects be synergis tic?