Context.—Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA.Objective.—To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine.Design.—Double-blind, controlled, randomized trial.Setting.—University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada, and Australia (INCAS).Patients.—Antiretroviral therapy–naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60×109/L (200-600/µL).Intervention.—Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine.Main Outcome Measure.—Plasma HIV-1 RNA.Results.—Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death were 23% (11/47), 25% (13/53), and 12% (6/51) for the zidovudine plus nevirapine, zidovudine plus didanosine, and triple drug therapy groups, respectively (P=.08).Conclusions.—Triple drug therapy with zidovudine, didanosine, and nevirapine led to a substantially greater and sustained decrease in plasma viral load than the 2-drug regimens studied. Our results also suggest that suppression of viral replication, as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of quantitation of the most sensitive test available, may at least forestall the development of resistance.
To the Editor The impact of electronic cigarette (e-cigarette) use on health is frequently cited as an urgent research need. 1 Population-based, longitudinal cohort studies can provide necessary evidence to inform researchers and the general public about potential health risks that e-cigarettes may pose.However, such studies frequently rely on self-reported data to infer e-cigarette user status, and such reports may not be completely accurate. 2Furthermore, there are populations that frequently misreport tobacco use, many of which constitute vulnerable groups, such as pregnant women and youth. 3,4Currently, data are lacking with respect to whether e-cigarette users may misreport occasional smoking.Recently, a study by Rubinstein et al. 5 raised serious concerns regarding adolescents who vape e-cigarettes that also reported no tobacco cigarette use.In their study, self-reported e-cigarette users were found to have detectable levels of tobacco-specific biomarkers, suggesting that there may be potential issues in relying exclusively on self-reported data to establish tobacco use.We investigated this problem among adults by estimating the proportion of e-cigarette users that may be misreporting their smoking status.
Sex and racial/ethnic identity-specific cut-points for validating tobacco use using Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and total nicotine equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use.
