A Phase IV Study of Antiretroviral Therapy for HIV Infected Adults Presenting With Acute Opportunistic Infections: Immediate Versus Deferred Initiation of Antiretroviral Therapy

Brief Summary

Detailed Description

Despite the advent of highly active antiretroviral therapy (HAART), many HIV infected patients without access to antiretroviral therapy (ART) present with acute OIs. Such presentations pose a management problem, as there are currently no data available as to whether initiating HAART during the acute presentation is of benefit. Reports of an immune reconstitution inflammatory syndrome (IRIS) marked by increasing hypoxia or new pulmonary infiltrates have been associated with the initiation of ART in patients with AIDS. There is also concern as to drug interactions between ART and antimicrobials used to treat the presenting OI. This study will evaluate the possible benefits and costs of initiating ART in HIV infected patients who present with an AIDS-defining OI. There are 2 steps in this study. In Step 1, patients will be randomly assigned to one of two study arms. Arm A will receive ART within 2 weeks of starting therapy for the acute OI. Arm B will have ART deferred until Step 2, at least 4 weeks and no more than 32 weeks after beginning therapy for the acute OI. Only Arm B participants will enter Step 2, which will likely begin between Weeks 6 and 12. The study will make the following drugs available for construction of an antiretroviral (ARV) regimen: emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), lopinavir/ritonavir (LPV/RTV), and stavudine (d4T). Use of other ARV drugs is at the discretion of the study official. Drug regimen additions and substitutions will be made on a case-by-case basis. Patients will be followed for 48 weeks and will have 10 study visits. All study visits will include a physical exam, medication history, and blood collection. Patients will be asked to complete questionnaires assessing health status and adherence at selected visits.

Primary Outcomes

Secondary Outcomes

• HIV-1 plasma viral load at all timepoints up to and including Week 48
• CD4 counts at all timepoints up to and including Week 48
• changes in ARV regimen for lack of efficacy
• efficacy of treatment and clinical outcomes for specific OI/BI, including duration of and complications of treatment, incidence and duration of hospitalization, rate of relapse/recurrence, and incidence of IRIS and impact on outcomes in the two arms
• safety and tolerability, measured by Grade 3 and 4 signs and symptoms and laboratory toxicities, ART and OI/BI treatment changes and dose modifications due to toxicities, and IRIS
• HIV-1 drug resistance over time (genotype)
• health care resource use, including total inpatient days and emergency room visits compared in the two groups
• quality of life (QOL) and functional status outcomes, including overall self-reported QOL and functional status compared in the two groups at Week 48
• adherence, including self-reported adherence to all ARVs over the study period, examined for relationship with primary study outcomes, including death, progression, and viral suppression