A Study of HIV-Disease Development in Aging

The purpose of this study is to better understand the relationship between age and HIV disease progression.

This study will explore the possible relationship between age and HIV disease progression. Older age is an important risk factor for faster disease development, but older people may respond better to combination drug therapy. This relationship needs to be understood better.

Older age is an important risk factor for accelerated HIV-disease progression. However, the virologic response to highly active antiretroviral therapy (HAART) may be superior in older persons. A better understanding of the immunologic, virologic, and behavioral mechanisms that underlie these age-related differences may help to elucidate critical immune responses that are necessary to control the progression of HIV-disease.

Patients are grouped according to age. Group A consists of patients between the ages of 13 and 30 years. Group B consists of patients age 45 years or older. All patients receive open-label lopinavir/ritonavir (LPV/RTV) plus emtricitabine (FTC) plus stavudine (d4T) for 96 [AS PER AMENDMENT 06/04/02: 192] weeks. Study visits occur at pre-entry, entry, and Weeks 4, 8, 12, 16, and 24 then every 12 weeks thereafter through Week 96 [AS PER AMENDMENT 06/04/02: Week 192]. Clinical assessments, safety laboratory tests, CD4 cell count monitoring, lymphocyte phenotyping, and HIV-1 RNA determinations are performed routinely. Blood samples are stored for further immunology and virology studies. Patients may volunteer to participate in virology substudy A5020s and either immunology substudy A5016s or A5017s [AS PER AMENDMENT 06/04/02: Substudy A5017s has been eliminated.]

• Drug: Lopinavir/Ritonavir
• Drug: Emtricitabine
• Drug: Stavudine

• Kalayjian R, Landay A, Pollard R, Pu M, Spritzer J, Tebas P, Gross B, Valcour V, Cu-Uvin S, Fiscus S, Fidel P, Wu A, Fox L, Stocker V, Lederman M, and AIDS Clinical Trials Group Protocol 5015. ACTG 5015: NaIve T-cell Reconstitution is Associated with Immune Activation. CROI 2004. Abstract 232.
• Tenorio AR, Spritzler J, Martinson J, Gichinga CN, Pollard RB, Lederman MM, Kalayjian RC, Landay AL. The effect of aging on T-regulatory cell frequency in HIV infection. Clin Immunol. 2009 Mar;130(3):298-303. Epub 2008 Nov 12.

Inclusion Criteria

Patients may be eligible for this study if they:

• Are HIV-positive.
• Are between 13 and 30 years old (need consent of parent or guardian if under 18), or are more than 44 years of age.
• Have a viral load of more than 2000 copies/ml within 60 days of study entry.
• Have a CD4 cell count of less than 600 cells/mm3 within 60 days of study entry. (This reflects a change in the CD4 cell count requirement.)
• Agree to use effective methods of birth control (such as condoms) during and for 12 weeks after the study.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Are pregnant or breast-feeding.
• Have an AIDS-related cancer (except Kaposi's sarcoma) requiring chemotherapy.
• Have hepatitis within 30 days of study entry.
• Have diarrhea (more than 3 liquid stools/day for at least 14 days) within 30 days of study entry.
• Are receiving chemotherapy or radiation treatment.
• Have taken antiretroviral drugs for more than 14 days.
• Have received an HIV vaccine within 30 days of study.
• Have a serious illness or infection within 14 days of the study.
• Have other serious conditions that might interfere with study participation.
• Have taken or plan to take certain other drugs that might affect the study results.