Discontinuation of Antiretroviral Therapy in Patients With Asymptomatic HIV Infection

Predictors of Immunologic and Clinical Progression in Subjects With CD4+ Cell Counts Greater Than 350 Cells/mm3 Who Discontinue Antiretroviral Therapy

The purpose of this study is to determine whether patients who have asymptomatic HIV infection can discontinue antiretroviral therapy (ART) without adverse clinical, virologic, or immunologic consequences. This study will also assess the virologic, immunologic, and clinical outcomes in any patients who restart ART.

Patients who can discontinue ART without a significant loss of virologic or immunologic control and without an increase in clinical events may be spared the expense and adverse effects of treatment. However, the consequences of treatment discontinuation in patients with asymptomatic HIV infections are not well understood. This study will follow the clinical and immunologic progression of HIV infection in patients who have low HIV viral load and preserved CD4+ cell counts at the time ART is stopped.

Patients will fast for at least 8 hours prior to the first study visit. At this visit, blood will be drawn and body measurements will be taken. Patients will then discontinue their ART. Patients taking nonnucleoside reverse transcriptase inhibitors (NNRTIs) will stop taking NNRTIs 48 hours before withdrawing their other ART drugs. Study visits will occur every 4 to 8 weeks for the first year, then every 12 weeks for the second year. Blood will be taken at most visits, and patients will be asked to fast for at least 8 hours prior to Week 12 and 24 visits and again every 6 months. Patients who reinitiate ART for any reason will be registered to Step 2 and followed for 24 weeks.

Inclusion Criteria:

• HIV infection
• ART with 2 or more drugs for 6 or more months
• CD4+ cell count(s) > 350 cells/mm3 immediately prior to initiation of first ART
• CD4+ cell count > 350 cells/mm3 within 45 days prior to study entry
• Plasma viral load < 55,000 copies/ml within 45 days prior to study entry
• Willingness to discontinue ART at study entry
• Negative serum or urine pregnancy test within 14 days prior to study entry

Exclusion Criteria:

• Pregnancy or breast-feeding
• Systemic cancer chemotherapy, systemic investigational agents, or immunomodulators within 30 days prior to study entry
• Drug or alcohol use or dependence that would interfere with adherence to study requirements
• Illness requiring systemic treatment and/or hospitalization until the patient either completes therapy or has been clinically stable on therapy for at least 30 days prior to study entry
• Chronic medical condition that would have a negative impact on the participation of the patient or would be expected to result in significant use of the medical care system
• History of an HIV-related illness or complication in CDC categories B and C
• Nonadherence to ART
• Active infection with hepatitis B and currently taking adefovir at doses > 10 mg or 3TC and/or TDF