R D Moore

Data were analyzed from a multicenter observational cohort study of 1002 persons with AIDS or AIDS-related complex (ARC) and total CD4 cell count < 0.25 x 10(9)/L treated with zidovudine between April 1987 and April 1988. Cytomegalovirus (CMV) disease developed in 109 patients (10.9%), with a 2-year actuarial risk of 15%. Manifestations included retinitis (93 patients), esophagitis (10), colitis (8), gastritis (1), hepatitis (1), and encephalitis (1). The probability of CMV disease at 2 years for patients with initial counts < 0.1 x 10(9)/L was 21.4%, compared with 10.3% for patients with initial counts > or = 0.1 x 10(9)/L (P < .001). By proportional hazards analysis, baseline CD4 cell count < 0.1 x 10(9)/L, enrollment diagnosis of AIDS, and homosexuality were significantly associated with subsequently developing CMV disease. Median survival after diagnosis of CMV disease was 173 days, and CMV was an independent predictor of death. CMV contributes to AIDS-related morbidity and mortality. As new anti-CMV drugs become available, prophylaxis should be targeted at individuals with CD4 cell counts < 0.1 x 10(9)/L.

RATIONALE: Respiratory syncytial virus (RSV) is the leading cause of childhood lower respiratory infection, yet viable therapies are lacking. Two major challenges have stalled antiviral development: ethical difficulties in performing pediatric proof-of-concept studies and the prevailing concept that the disease is immune-mediated rather than being driven by viral load. OBJECTIVES: The development of a human experimental wild-type RSV infection model to address these challenges. METHODS: Healthy volunteers (n = 35), in five cohorts, received increasing quantities (3.0-5.4 log plaque-forming units/person) of wild-type RSV-A intranasally. MEASUREMENTS AND MAIN RESULTS: Overall, 77% of volunteers consistently shed virus. Infection rate, viral loads, disease severity, and safety were similar between cohorts and were unrelated to quantity of RSV received. Symptoms began near the time of initial viral detection, peaked in severity near when viral load peaked, and subsided as viral loads (measured by real-time polymerase chain reaction) slowly declined. Viral loads correlated significantly with intranasal proinflammatory cytokine concentrations (IL-6 and IL-8). Increased viral load correlated consistently with increases in multiple different disease measurements (symptoms, physical examination, and amount of nasal mucus). CONCLUSIONS: Viral load appears to drive disease manifestations in humans with RSV infection. The observed parallel viral and disease kinetics support a potential clinical benefit of RSV antivirals. This reproducible model facilitates the development of future RSV therapeutics.

To evaluate the association between acyclovir use and survival in patients with advanced human immunodeficiency virus infection, observational data from 1044 persons with AIDS or AIDS-related complex (ARC) and < or = 250 CD4 cells/mm3 following initiation of zidovudine were analyzed. Of these patients, 336 (32%) received regular acyclovir (> or = 6 weeks in 2 months). There were no differences in mortality data between acyclovir users and nonusers overall or when analyzed from 1 year after first use of zidovudine, from time of AIDS in those with ARC at enrollment, from patients with AIDS or < 100 CD4 cells/mm3 at enrollment, or from patients taking acyclovir for up to 10 months. Acyclovir use was associated with increased mortality (relative hazard, 1.28; P = .057) independent of herpesvirus infections and of other characteristics associated with mortality. In this study, the use of acyclovir at doses for treatment of herpes simplex virus infection in combination with zidovudine was not associated with prolonged survival.

SETTING: The developing world. OBJECTIVE: To compare the strategy of TB vaccination with that of tuberculin skin-testing in conjunction with isoniazid (INH) in preventing tuberculosis in HIV-infected persons. For any clinical scenarios in which immunization would be more effective than INH preventive therapy, to determine the minimum necessary vaccine safety and effectiveness required. DESIGN: Decision analysis. A hypothetical cohort of 10000 HIV-infected persons, 65% of whom were tuberculin positive, living in the developing world, was studied. Probability estimates were based on BCG vaccine for the baseline analysis, and it was assumed that the vaccine cannot protect if given after infection. RESULTS: Under the probability estimates and assumptions of the analysis, tuberculin skin testing/INH preventive therapy would prevent 458 more cases of TB and 45 more deaths due to TB than TB vaccination. One- and two-way sensitivity analyses revealed no thresholds at which TB vaccination would be the preferred strategy. Vaccine safety did not impact the outcome of the analysis. Three-way sensitivity analysis revealed that if the prevalence of anergy were 35% and the risk of progression to active TB among anergic persons 12.2 cases per 100 person-years, a vaccine would have to be at least 87% effective to be preferred over INH preventive therapy. CONCLUSIONS: Under the conditions of the analysis, which did not account for cost or logistics, tuberculin skin testing/INH preventive therapy would be more effective than TB vaccination in preventing TB among HIV-infected persons. The hypothesized TB vaccine would prevent more TB than INH preventive therapy only in areas where the prevalence of anergy and risk of active TB if anergic were high, and vaccine effectiveness exceeded 87%.