Table of Contents

• The NEAT Study: A 48-Week Open-Label Study to Compare the Antiviral Efficacy and Safety of GW433908 Versus Nelfinavir in Antiretroviral Therapy-Naive HIV-1-Infected Patients
• Acquired Immunodeficiency Syndrome and the Risk of Stroke
• Stable Partnership and Progression to AIDS or Death in HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy: Swiss HIV Cohort Study
• Evaluation of the Impact of Highly Active Antiretroviral Therapy on Immune Recovery in Antiretroviral Naive Patients

The NEAT Study: A 48-Week Open-Label Study to Compare the Antiviral Efficacy and Safety of GW433908 Versus Nelfinavir in Antiretroviral Therapy-Naive HIV-1-Infected Patients

Rodriguez-French A et al

Objective: To compare the efficacy, durability, and tolerability of GW433908 (908) 1,400 mg twice daily (BID), with nelfinavir (NFV) 1,250 mg BID.

Methods: This was an international, multicenter, randomized, open-label study (NEAT) in antiretroviral therapy (ART)-naive HIV-infected adults with plasma HIV-1 RNA (vRNA) at screening >5,000 copies/mL. Patients were randomly assigned to 908 or NFV (2:1) for a minimum of 48 weeks, with a background of abacavir (ABC) and lamivudine (3TC).

Results: A total of 166 patients received randomized treatment with 908 BID and 83 received NFV BID. The population was diverse with regard to race and gender (76 percent Hispanics and blacks, 31 percent female) and had advanced HIV disease at screening (45 percent had vRNA >100,000 copies/mL, 48 percent had CD4 counts <200 cells/mm³, 20 percent had a history of [US Centers for Disease Control and Prevention] class C events). After 48 weeks of study by an intention-to-treat rebound or discontinuation = failure analysis, a greater proportion of patients in the 908 BID group (66 percent) than the NFV BID group (51 percent) achieved vRNA <400 copies/mL. Furthermore, more patients with screening vRNA >100,000 copies/mL (67 percent versus 35 percent) or CD4 <50 cells/mm³ (48 percent versus 24 percent) achieved undetectable viral loads taking 908 BID compared with NFV BID, respectively. Favorable immunologic responses were observed for both groups. Diarrhea, which was more common in the NFV BID group (18 percent versus 5 percent), was the only drug-related grade 2-4 adverse event with a significant difference (P=0.002) in incidence between groups.

Conclusion: Administration of 908 BID resulted in a potent and sustained antiretroviral response, notably in antiretroviral treatment-naive patients with advanced HIV disease. GW433908 was generally well tolerated and provides a convenient dosing option without food or fluid restrictions. [JAIDS 2004;35(1):22-32.]

Acquired Immunodeficiency Syndrome and the Risk of Stroke

Cole JW et al

Background: Although acquired immunodeficiency syndrome (AIDS) is thought to increase the risk of stroke, few data exist to quantify this risk. This is the first population-based study to quantify the AIDS-associated risk of stroke.

Methods: We identified all incident ischemic stroke (IS) and intracerebral hemorrhage (ICH) cases among young adults 15 to 44 years of age in central Maryland and Washington, DC, who were discharged from any of the 46 hospitals in the study area in 1988 and 1991. Using data from the medical records, two neurologists reviewed each case to confirm the diagnosis. Cases of AIDS among these patients with stroke were defined using Centers for Disease Control and Prevention criteria (1987). The number of cases of AIDS in the central Maryland and Washington population during 1988 and 1991 was determined from regional health departments working with the Centers for Disease Control and Prevention. Poisson regression was used to estimate the age-, race-, and sex-adjusted relative risk of stroke associated with AIDS.

Results: There were 385 IS cases (six with AIDS) and 171 ICH cases (six with AIDS). The incidences of IS and ICH among persons with AIDS were both 0.2 percent per year. AIDS conferred an adjusted relative risk of 13.7 (95 percent confidence interval [CI], 6.1 to 30.8) for IS and 25.5 (95 percent CI, 11.2 to 58.0) for ICH. After exclusion of five cases of stroke in AIDS patients in whom other potential causes were identified, AIDS patients continued to have an increased risk of stroke with an adjusted relative risk of 9.1 (95 percent CI, 3.4 to 24.6) for IS and 12.7 (95 percent CI, 4.0 to 40.0) for ICH.

Conclusions: This population-based study found that AIDS is strongly associated with both IS and ICH. [Stroke 2004;35(1):51-56.]

Stable Partnership and Progression to AIDS or Death in HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy: Swiss HIV Cohort Study

Young J et al

Objectives: To explore the association between a stable partnership and clinical outcome in HIV-infected patients receiving highly active antiretroviral therapy (HAART).

Design: Prospective cohort study of adults with HIV (Swiss HIV cohort study).

Setting: Seven outpatient clinics throughout Switzerland.

Participants: The 3,736 patients in the cohort who started HAART before 2002 (median age 36 years, 29 percent female, median follow-up 3.6 years).

Main Outcome Measures: Time to AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at least 50 and 100 above baseline, optimal viral suppression (a viral load below 400 copies/ml), and viral rebound.

Results: During follow-up 2,985 (80 percent) participants reported a stable partnership on at least one occasion. When starting HAART, 52 percent (545/1,042) of participants reported a stable partnership; after five years of follow-up 46 percent (190/412) of participants reported a stable partnership. In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95 percent confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without. Adjusted hazards ratios for other endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24) for an increase in CD4 cells of 100 counts/µl or more, and 1.06 (0.98 to 1.14) for optimal viral suppression.

Conclusions: A stable partnership is associated with a slower rate of progression to AIDS or death in HIV-infected patients receiving HAART. [BMJ 2004;328(7430):15.]

Evaluation of the Impact of Highly Active Antiretroviral Therapy on Immune Recovery in Antiretroviral Naive Patients

Al-Harthi L et al

Objectives: To examine the extent of immune reconstitution in treatment-naive patients with CD4 T-cell counts <500 cells/mm³ following 48 weeks of highly active antiretroviral therapy (HAART).

Methods: Thirteen antiretroviral naive patients were evaluated longitudinally for 48 weeks on HAART utilizing immune functional and lymphocyte phenotyping assays, including lymphocyte proliferation assay, flow cytometric evaluation of cell surface markers, and delayed type hypersensitivity skin tests. Virologic responses were monitored using commercially available viral load assays and gag/pol mRNA quantification using simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function was evaluated for a subset of four patients using real-time polymerase chain reaction (PCR) for T-cell receptor excision circle (TREC) quantification and thymic scans using computerized axial tomography (CT) of the thymus.

Results: HAART initiation resulted in a significant decline in plasma viremia and percentage of infected peripheral blood cells, and a rise in CD4 T cells from a baseline median of 207 cells/mm³ to a week-48 median of 617 cells/mm³. The rise was predominately in CD4 memory cells. Naive T cells also increased in number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were elevated at baseline (24 and 62 percent, respectively) and declined by week 48 (17 and 36 percent, respectively) but did not reach normal levels. The number of Fas CD4 T cells increased from a baseline median of 169 to 381 cells/mm³ at week 48. Both soluble interleukin (IL)-2 and tumor necrosis factor (TNF) II receptors declined by week 48. HIV p24 lymphocyte proliferation assay responses were transiently detected in three patients. TREC values increased from a median 6,400 copies/microg at baseline to a week-48 median value of 26,697 copies/microg.

Conclusion: Immune functional reconstitution was not achieved in these HAART-naive patients. [HIV Med 2004;5(1):55-65.]