A national HIV community cohort: design, baseline, and follow-up of the AmFAR Observational Database. American Foundation for AIDS Research Community-Based Clinical Trials Network.

This article describes the design, methodology, baseline distributions, and general follow-up characteristics of the American Foundation for AIDS Research (AmFAR) National Observational Database (ODB) Project including the benefits and limitations of collecting information on a large simple cohort in the HIV community setting. The study prospectively followed 15,611 HIV-positive men and women and collected longitudinal and cross-sectional data on demographics, medical conditions, drug therapies, laboratory parameters, and survival. Participants were followed between October 1990 and December 1993 by 252 community-based sites coordinated by 22 centers in the Community-Based Clinical Trials Network (CBCT Network) throughout the United States (including Puerto Rico) and Toronto, Canada. The ODB provided quantitative information on a national level needed to track the HIV epidemic and plan clinical trials conducted through the Network, and to provide sites with local databases to monitor patients and facilitate access to therapies in clinical trials. Overall, the ODB contains information on 1,925 women (12%) and 13,686 men (88%), 60% white, 20% African American, 17% Latino/Hispanic, with 56,254 baseline and follow-up forms, a median follow-up of about 12 months, a 16% loss-to-follow-up, and an 11% mortality rate. AmFAR plans to place the ODB in the public domain.

Experience with the use of a first-line regimen of stavudine, lamivudine and nevirapine in patients in the TREAT Asia HIV Observational Database.

BACKGROUND: The antiretroviral treatment (ART) combination of stavudine, lamivudine and nevirapine (d4T/3TC/NVP) is the most frequently used initial regimen in many Asian countries. There are few data on the outcome of this treatment in clinic cohorts in this region. METHODS: We selected patients from the TREAT Asia HIV Observational Database (TAHOD) who started their first ART regimen with d4T/3TC/NVP. Treatment change was defined as cessation of therapy or the addition or change of one or more drugs. Clinical failure was defined as diagnosis with an AIDS-defining illness, or death while on d4T/3TC/NVP treatment. RESULTS: The rate of treatment change among TAHOD patients starting d4T/3TC/NVP as their first antiretroviral treatment was 22.3 per 100 person-years, with lower baseline haemoglobin (i.e. anaemia) associated with slower rate of treatment change. The rate of clinical failure while on d4T/3TC/NVP treatment was 7.3 per 100 person-years, with baseline CD4 cell count significantly associated with clinical failure. After d4T/3TC/NVP was stopped, nearly 40% of patients did not restart any treatment and, of those who changed to other treatment, the majority changed to zidovudine (ZDV)/3TC/NVP and less than 3% of patients changed to a protease inhibitor (PI)-containing regimen. The rates of disease progression on the second-line regimen were similar to those on the first-line regimen. CONCLUSION: These real-life data provide an insight into clinical practice in Asia and the Pacific region. d4T/3TC/NVP is maintained longer than other first-line regimens and change is mainly as a result of adverse effects rather than clinical failure. There is a need to develop affordable second-line antiretroviral treatment options for patients with HIV infection in developing countries.

Cytomegalovirus resistance. Public health implications of CMV prophylaxis and treatment in the HIV patient population.

AIDS: The treatment and prevention of cytomegalovirus (CMV) in HIV-positive patients is a critical issue. CMV, a type of herpes virus, is transmitted by kissing, sexual intercourse, and blood transfusion. In people with healthy immune systems, CMV can be harbored for years in a latent stage. In HIV-positive patients, it is a major health threat that can lead to pneumonia, intestinal and nervous system diseases, and blindness. CMV retinitis occurs in 25 percent of AIDS patients. Ganciclovir and foscarnet are used to treat CMV retinitis, and another treatment, cidofovir, is in clinical studies. A conference held in January 1996, sponsored by the American Foundation for AIDS Research (AmFAR), addressed the issue of CMV resistance to antiviral drugs. Pharmaceutical companies are currently developing viral assay tests to measure the amount of CMV in the blood. An viral load increase indicates resistance. A new compound, 2922, from the ISIS Pharmaceutical Company seems to block CMV replication without developing resistance.^ieng

Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis Carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ.

Trimethoprim-sulfamethoxazole (TMP-SMZ) is the most effective Pneumocystis carinii pneumonia (PCP) prophylactic agent, but adverse reactions are common among human immunodeficiency virus (HIV)-infected patients and limit its use. This randomized, double-blind controlled trial compared 2 methods of TMP-SMZ reintroduction, 6-day dose escalation and direct rechallenge, for PCP prophylaxis in HIV-infected patients who had experienced previous treatment-limiting reactions. The primary end point was the ability to take single-strength TMP-SMZ daily for 6 months. Seventy-five percent of the dose-escalation group and 57% of the direct-rechallenge group continued to receive daily single-strength TMP-SMZ for 6 months (P= .014). Among premature discontinuations, 58% of the dose-escalation group and 70% of the direct-rechallenge group were due to adverse reactions. None of these reactions was serious. This study provides evidence that it is possible to successfully reintroduce TMP-SMZ to a significant proportion of HIV-infected patients who have experienced mild-to-moderate treatment-limiting adverse reactions.

A randomized study of the safety and antiretroviral activity of hydroxyurea combined with didanosine in persons infected with human immunodeficiency virus type 1. American Foundation for AIDS Research Community-Based Clinical Trials Network.

This randomized open-label trial of human immunodeficiency virus type 1-infected persons compared safety and efficacy for 38 patients receiving hydroxyurea/didanosine combination therapy with findings in 42 persons given didanosine monotherapy for 12 weeks, followed by 12 weeks of hydroxyurea/didanosine combination therapy for all patients. Week 12 on-treatment group comparisons showed a mean decrease in virus load between hydroxyurea/didanosine versus didanosine groups of -0.93 versus -0.74 log10 copies/mL (P=.20); a higher percentage of the hydroxyurea/didanosine group below the assay's detection limit (500 copies/mL), 29% versus 7% (P=.017); and median change in CD4 cells for the hydroxyurea/didanosine versus didanosine group of 0 versus 43 cells/mm3 (P=.045), although median change in CD4 percentage was similar (0.9% vs. 1.2%, P=.64). Week 24 virus load reductions and CD4 cell changes were similar in both groups. Intent-to-treat and on-treatment analyses showed similar results. The hydroxyurea/didanosine combination was well tolerated.