The capacity of HIV-1 to establish latent infection of CD4+ T cells may allow viral persistence despite immune responses and antiretroviral therapy. Measurements of infectious virus and viral RNA in plasma and of infectious virus, viral DNA and viral messenger RNA species in infected cells all suggest that HIV-1 replication continues throughout the course of infection. Uncertainty remains over what fraction of CD4+ T cells are infected and whether there are latent reservoirs for the virus. We show here that during the asymptomatic phase of infection there is an extremely low total body load of latently infected resting CD4+ T cells with replication-competent integrated provirus (<10(7) cells). The most prevalent form of HIV-1 DNA in resting and activated CD4+ T cells is a full-length, linear, unintegrated form that is not replication competent. The infection progresses even though at any given time in the lymphoid tissues integrated HIV-1 DNA is present in only a minute fraction of the susceptible populations, including resting and activated CD4+ T cells and macrophages.

Tenofovir DF is an antiviral nucleotide with activity against human immunodeficiency virus type 1 (HIV-1). The pharmacokinetics, safety, and activity of oral tenofovir DF in HIV-1-infected adults were evaluated in a randomized, double-blind, placebo-controlled, escalating-dose study of four doses (75, 150, 300, and 600 mg given once daily). Subjects received a single dose of tenofovir DF or a placebo, followed by a 7-day washout period. Thereafter, subjects received their assigned study drug once daily for 28 days. Pharmacokinetic parameters were dose proportional and demonstrated no change with repeated dosing. Reductions in plasma HIV-1 RNA were dose related at tenofovir DF doses of 75 to 300 mg, but there was no increase in virus suppression between the 300-and 600-mg dose cohorts, despite dose-proportional increases in drug exposure. Grade III or IV adverse events were limited to laboratory abnormalities, including elevated creatine phosphokinase and liver function tests, which resolved with or without drug discontinuation and without sequelae. No patients developed detectable sequence changes in the reverse transcriptase gene.

Background Opioid dependence is common in HIV clinics. Buprenorphine/naloxone (BUP) is an effective treatment for opioid dependence that may be used in routine medical settings. Objective To compare clinic-based treatment with BUP (clinic-based BUP) with case-management and referral to an opioid treatment program (referred-treatment). Design Single-center, 12-month randomized trial. Participants and investigators were aware of treatment assignments. Setting HIV clinic in Baltimore, Maryland. Patients 93 HIV-infected, opioid-dependent subjects who were not receiving opioid agonist therapy and were not dependent on alcohol or benzodiazepines. Intervention The clinic-based BUP strategy included BUP induction and dose titration, urine drug test monitoring, and individual counseling; the referred-treatment arm included case management and referral to an opioid treatment program. Measurements Initiation and long-term receipt of opioid agonist therapy, urine drug test results, visit attendance with primary HIV providers, use of antiretroviral therapy, and changes in HIV RNA levels and CD4 cell counts. Results The average estimated participation in opioid agonist therapy was 74% (95% CI 61%–84%) in clinic-based BUP and 41% (29%–53%) in referred-treatment (p<0.001). Opioid and cocaine positive urine drug tests were significantly less frequent in clinic-based BUP than in referred-treatment, and study subjects in clinic-based BUP attended significantly more HIV primary care visits than study subjects in referred-treatment. Use of antiretroviral therapy and changes in HIV RNA levels and CD4 cell counts did not differ in the 2 arms of the study. Limitations This was a small single-center study, follow-up was only fair, and there was an imbalance in recent drug injection in the study arms at baseline. Conclusions This study suggests that management of HIV-infected, opioid-dependent patients with a clinic-based BUP strategy facilitates access to opioid agonist therapy and improves substance abuse treatment outcomes. Primary Funding Source Health Resources Services Administration, Special Projects of National Significance.