This protocol is an exploratory study of HIV expression in patients who are receiving highly active antiviral therapy and who have low viral loads below or near the current limit of detection (50 copies/ml plasma). Recent studies have suggested that patients with suppressed viral loads in this low range have continued HIV expression, but the amount and the origin of this virus remains unknown. The amount of virus expression in plasma is uncertain because the current viral load assays are imprecise in the cutoff range of 50-75 copies/ml plasma. The origin of the HIV found at low viral loads detected is unknown as well; two possible sources of virus include expression from long-lived reservoirs of infected cells, and low level spreading infection to uninfected cells. Determining the origin of HIV expression has clinical importance; currently available HIV drug therapy will have little effect on HIV expression from established reservoirs, but more potent HIV therapy could potentially inhibit a spreading HIV infection.
In this study we plan two principal objectives. First, we will investigate the level of HIV expression in plasma samples at low viral loads using a new HIV load assay with enhanced sensitivity and precision in the viral load range of 1-100 copies. If data from the survey confirms acceptable performance characteristics for this assay we will proceed with stage II of the protocol. In stage II we plan to determine, in several short-term intensification approaches to investigate whether the incorporation of an additional antiretroviral to suppressive HAART regimens ("intensification HAART") will further suppress plasma virus. In a small pilot study, we will plan to intensify regimens for 30 days in a nonrandomized fashion. Secondly, we plan to study patients who are switching medications for preference or mild toxicity. In these patients we will intensify their regimens for 30 days in an overlap fashion, adding the new drug instead of switching medications. After 30 days of drug overlap, we will continue the new drug and discontinue the identified antiretroviral. These initial studies will assist in obtaining initial data and confirming the estimated sample size of a larger, randomized study to rigorously investigate the virologic effects of drug intensification. If these initial proof-of-concept experiments suggest that HIV may be suppressed by intensification HAART, then we plan to expand the study in a larger controlled trial to determine the degree of suppression possible with intensification therapy.
As a secondary objective we will investigate whether it is feasible to study HIV genetic variation in samples from patients with suppressed viral loads using molecular techniques developed to study HIV variation in patients with viral loads greater than 1000 copies/ml plasma (protocol 00-I-0110).
We plan to enroll up to 70 patients in a viral load survey cohort of HIV viral loads, and analyze a series of samples from completed trials of antiretroviral therapy.
