PACTG P1015: INTENSIFICATION OF HIV-SPECIFIC CD4 & CD8 ACTIVITY BY CYCLING HAART

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PACTG 1015 is a proof of concept study to determine the effects of suspending HAART on CD4 and CD8 activity in HIV-positive children and adolescents who have achieved viral suppression of < 50 HIV RNA copies/ml. It is hypothesized that a brief and low level increase in HIV viremia, resulting from suspension of HAART might boost HIV-specific CD8 and CD4 T cells. After the subsequent suppression of viremia with the reintroduction of HAART, the expanded CD8 population might be able to better control viral replication or to eliminate some of the cell-associated HIV. This could result in a more prolonged period of aviremia with a subsequent suspension of HAART. The study will initially enroll children and adolescents > 4 and < 21 years of age; after safety of the approach is demonstrated in this age group, cohhort II will open and enroll children > 2 and < 4 years of age. Within each age cohort there are two groups: one that will cycle on and off HAART (Group A) and a control group that will remain on continuous HAART (Group B). Subjects in Group B will be those who do not choose to enter Group A. Subjects in Group A will participate in cycles that alternate the time on antiviral medication with time off of the medication (drug holiday). The first interruption (cycle 1) will be for three days. Each subsequent interruption will add two days (cycle n+2 days). At the end of the drug holiday, the subjects' viral load will be tested. During the following week, the subjects' resume their HAART therapy while waiting for the viral load results. If it remains below the level of detection, they will begin the next cycle. If their plasma viral load becomes detectable at the end of the drug holiday, they will move to the detectable virus cycle and will remain on antiviral therapy for 28 days. Any subject in a detectable virus cycle is moved to the next drug holiday cycle if they are able to suppress their viral load. If they are not able to suppress their viral load, they remain on the 28-day treatment (also called detectable virus cycle) for a maximum of 4 cycles. If subjects fail four treatment cycles (i.e. they still have a confirmed detectable plasma viremia after 112 days of continuous HAART), they will be taken off study. Resistance testing will be performed when viral load exceeds 500 cp/ml. The control group of subjects who do not undergo discontinuation of their therapy will also be evaluated with routine plasma viremia measured every three months as well as more advanced immunologic and virologic assays.