• Doubling in HIV Pol-specific CD8 cells, measured by ELISPOT [ Time Frame: Through Day 28 ] [ Designated as safety issue: No ]
• Increase in CMV pp65 CD8 cells, measured by ELISPOT in the thalidomide treatment group [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
• Increase in HIV p24-specific IFN-gamma-secreting CD4 cells in the thalidomide treatment group, measured by fluorescence-activated cell sorting (FACS) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
• Increase in cytomegalovirus (CMV)-specific interferon (IFN)-gamma-secreting CD4 T cells in the thalidomide treatment group, measured by FACS [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

• Doubling in HIV Pol-specific CD8 cells, measured by ELISPOT between Days 0 and 28 in the thalidomide treatment group
• increase in CMV pp65 CD8 cells, measured by ELISPOT in the thalidomide treatment group
• increase in HIV p24-specific IFN-gamma-secreting CD4 cells in the thalidomide treatment group, measured by fluorescence-activated cell sorting (FACS)
• increase in cytomegalovirus (CMV)-specific interferon (IFN)-gamma-secreting CD4 T cells in the thalidomide treatment group, measured by FACS

• Increase in the frequency of keyhole limpet hemocyanin (KLH)-specific lymphocyte proliferative responses in the thalidomide treatment group [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
• Increase in adverse events in the thalidomide treatment group [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

• Increase in the frequency of keyhole limpet hemocyanin (KLH)-specific lymphocyte proliferative responses in the thalidomide treatment group
• increase in adverse events in the thalidomide treatment group

Despite treatment with anti-HIV drugs, people infected with HIV continue to have problems with their immune systems. This study will evaluate whether the drug thalidomide, which stimulates the immune system's T cells, can improve immune system function in people with HIV.

In patients with chronic HIV infection, HIV replication and abnormalities in immune function persist following treatment with highly active antiretroviral therapy (HAART). Specifically, costimulatory T cell interactions are impaired. The immune modulatory drug thalidomide was recently found to costimulate T cells. Pharmacologic T cell costimulation may compensate for the T cell deficiencies in people with HIV disease and improve immune function. This study will test whether thalidomide treatment enhances HIV and cytomegalovirus (CMV)-specific immunity in patients with HIV and CMV, and will evaluate the effect of thalidomide on HIV replication.

In this study, 40 HIV and CMV infected patients on HAART and 40 HIV uninfected CMV seropositive controls will be randomly assigned to low dose thalidomide or placebo treatment for 28 days. T cell responses and HIV replication and genetic diversification will be assessed.

• Drug: Thalidomide
• Drug: Thalidomide placebo

• Experimental: Participants will receive low dose thalidomide for 28 days
• Placebo Comparator: Participants will receive low dose thalidomide placebo for 28 days

• Haslett PA, Hanekom WA, Muller G, Kaplan G. Thalidomide and a thalidomide analogue drug costimulate virus-specific CD8+ T cells in vitro. J Infect Dis. 2003 Mar 15;187(6):946-55. Epub 2003 Mar 6.
• Haslett PA, Klausner JD, Makonkawkeyoon S, Moreira A, Metatratip P, Boyle B, Kunachiwa W, Maneekarn N, Vongchan P, Corral LG, Elbeik T, Shen Z, Kaplan G. Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients. AIDS Res Hum Retroviruses. 1999 Sep 1;15(13):1169-79.
• Matthews SJ, McCoy C. Thalidomide: a review of approved and investigational uses. Clin Ther. 2003 Feb;25(2):342-95. Review.

Inclusion Criteria

• HIV-infected for at least 5 years prior to study entry
• CD4 count of 300/mm3 or above
• Pre-HAART nadir CD4 count of 300/mm3 or less
• CMV infection
• HAART for 12 months prior to study entry
• Same effective HAART regimen for 3 months prior to study entry
• HIV viral load less than 200 copies/ml
• Clinically stable

Exclusion Criteria

• Active opportunistic infection
• Females of childbearing potential