Use of Combination Antiviral Therapy to Delineate the Identity and Longevity of Persistent Reservoirs of HIV-1 Infection and Replication
Indinavir
+ Zidovudine
+ Lamivudine
Blood-Borne Infections+11
+ Urogenital Diseases
+ Genital Diseases
Treatment Study
Summary
Study start date: March 3, 1997
Actual date on which the first participant was enrolled.The reservoirs of HIV-1 infection that permit maintenance of persistent virus infection (even when virus replication cannot be detected using sensitive assays to quantify plasma HIV-1 RNA levels) are currently unknown. Potential sites for persistent HIV-1 infection include cells with chronic or latent infections, cells present in locations within the body where antiviral drugs may not penetrate in levels sufficient to prevent additional cycles of de novo virus infection (e.g., the central nervous system), the presence of susceptible target cells for virus infection that may not metabolize certain antiviral drugs to their active inhibitory forms (e.g., macrophages), or extracellular (possible infectious) virus that may be retained on the surface of follicular dendritic cells within lymphoid organs. In an attempt to determine which, if any, of these potential reservoirs contribute to persistent HIV-1 infection, HIV-1-infected persons in two groups categorized by CD4+ T cell levels will be treated with concomitant administration of 4 antiviral drugs (zidovudine, lamivudine, indinavir and nevirapine) to accomplish maximal achievable suppression of virus replication. The rates of decay of virus and virus-infected cells following initiation of antiviral (and steroid) therapy will be monitored with sensitive, quantitative assays, and the identity and longevity of persistent sites of infection will be determined. This study may also illuminate to what extent HIV-1-induced immune system damage manifest as decreased CD4 T cell responses, a constricted repertoire of T cell antigen recognition, or as structural compromise of lymphoid tissue architecture can be reversed upon cessation of active HIV-1 replication by combinations of potent antiviral drugs.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.42 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
INCLUSION CRITERIA: Greater than or equal to 18 years old. Ability to sign informed consent and willingness to comply with study requirements and clinic policies. For women of child-bearing potential, negative result on pregnancy test within one week prior to initiating therapy. No medical contraindication to lymph node biopsy. HIV infection confirmed by ELISA and Western blot. Two CD4+ T cell counts less than 300/microliters within 3 months of beginning the protocol, with one of the two counts obtained at a screening history and physical examination performed 2 weeks prior to initiating therapy. Plasma HIV-1 RNA levels greater than 8000/ml. For participants with CD4 T cell counts greater than or equal to 300/microliter, asymptomatic for significant HIV-related illnesses. For participants with CD4 T cell counts less than or equal to 300/microliter no active opportunistic infections. For participants with greater than or equal to 300 CD4 cells/ microliter, no prior receipt of antiretroviral therapy. For participants with less than or equal to 300 CD4 cells/microliter, no prior use of lamivudine, nevirapine or protease inhibitors. Three or more palpable lymph nodes. Willingness to allow storage of samples for future research. Willingness to allow HLA testing. EXCLUSION CRITERIA: Platelet count less than 100,000 platelets/mm(3). PT or PTT (in the absence of documented anti-cardiolipin antibody) prolonged by greater than 2 seconds. Known underlying bleeding disorder. Pregnancy or breastfeeding. Psychiatric illness that might interfere with study compliance. Active substance abuse or history of prior substance abuse that may interfere with protocol compliance or compromise patient safety. Creatinine greater than 2. Liver function tests greater than 1.5 times the normal laboratory values. Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine history, physical examination, or screening laboratory studies.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, United StatesOpen National Institutes of Health Clinical Center, 9000 Rockville Pike in Google Maps