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To the Editor. —In their recent article, Dr Henrard and colleagues1show that human immunodeficiency virus (HIV) RNA levels, p24 antigenemia, and CD4 lymphocyte percentage independently predicted the risk of acquired immunodeficiency syndrome (AIDS), using Cox proportional hazards models with time-updated covariates. We wonder whether this conclusion is sensitive to different methods of fitting the model. In particular, we and others have found that the logarithm of the CD4 cell percentage provides a better fit to the model than the untransformed count. In the model fitted by Henrard et al, the relative difference in the risk of AIDS between patients with a CD4 lymphocyte percentage of 30% and 25% is assumed to be the same as that between patients with CD4 cell percentage of 10% and 5%. In comparison, if the logarithm of the CD4 cell percentage was used, the relative difference in the risk of AIDS between people

Objective. —To investigate whether high levels of depressive symptomatology at baseline predict more rapid decline of CD4 lymphocyte counts and progression of clinical disease in persons infected with the human immunodeficiency virus (HIV). Design. —Prospective cohort study with semiannual data collection waves and up to 66 months of follow-up. Setting. —Population-based probability sample of single men in areas of San Francisco with high case rates of the acquired immunodeficiency syndrome (AIDS). Subjects. —All 330 homosexual or bisexual men who by January 1985 had serological evidence of HIV infection but had not had an AIDS diagnosis. Analysis of CD4 lymphocyte change was performed for 277 subjects (83.9%) who had three or more CD4 lymphocyte counts recorded during the study period January 1985 through July 1990. Outcome Measures. —Depressive symptoms were assessed using the Center for Epidemiologic Studies—Depression scale (CES-D). All subjects were classified according to two indicators of depression: (1) as overall depressed using a cut point of 16 or higher on the complete CES-D, and (2) as affectively depressed using a cut point of more than 1 SD above the mean on a subscale of the CES-D measuring affective depression. Laboratory and symptom measures, antiretroviral use, demographics, and behavioral measures were also used. The primary outcome measure was the rate of change of the CD4 lymphocyte count. Secondary outcomes were AIDS-free survival and mortality. Results. —At baseline 65 subjects (19.7%) were classified as depressed on the overall scale and 53 (16.1%) were classified as depressed on the affective scale. The unadjusted mean rate of CD4 change was 38% greater for overall depressed subjects than for the overall nondepressed (−0.0812 vs −0.0588×10 9 /L[−81.2vs −58.8/μL per year; P =.07) and 34% greater for affectively depressed subjects than for the affectively nondepressed (−0.0804 vs −0.0598×10 9 /L per year; P =.06). In hierarchical multivariate analysis controlling for antiretroviral use, symptoms, and other predictors, baseline overall depression was associated with an excess decline in CD4 count of −0.0285×10 9 /L per year (95% confidence interval, −0.0496 to −0.0073), and baseline affective depression was associated with an excess decline in CD4 count of −0.0236×10 9 /L per year (95% confidence interval, −0.0464 to −0.0008). Neither overall depression nor affective depression was significantly associated with earlier AIDS diagnosis or earlier mortality. Conclusions. —Overall depression and affective depression predicted a more rapid decline in CD4 lymphocyte counts; this association was not attributable to baseline physiological differences. While the mechanism of the association remains unknown and cannot be addressed directly by this study, the data suggest that it can be explained neither as simply a reflection of perceived somatic symptoms nor as the result of differences in recreational drug and alcohol use. Further study is necessary to determine whether treating depression can alter the course of HIV infection. ( JAMA . 1993;270:2568-2573)

In Reply. —Dr Winkelstein raises the possibility of selection bias in our analysis of CD4 lymphocyte decline in the ALIVE cohort of IVDUs. This bias must always be a serious concern in any longitudinal study; for this reason and because the decline in CD4 lymphocytes in our cohort of IVDUs was lower than that reported by others, we looked for evidence of significant bias in our original analysis, as Winkelstein notes. However, we did not find such evidence, and we concluded that while the possibility of selection bias could not be completely excluded, a large bias did not appear likely, for the reasons already stated. We have recently updated the analysis of CD4 lymphocyte changes in our cohort based on an additional year of follow-up. Eighteen-month follow-up data are now available for 537 (85.7%) of the 627 cohort members, and the median rate of CD4 lymphocyte change is -7.4/μL per

The FDA has designated two additional investigational drugs for early availability for use in treatment under its Treatment IND (investigational new drug) program. Altogether 26 drugs have been designated for Treatment INDs since the mechanism was inaugurated in 1987 as a means of providing access prior to marketing approval to promising therapies for serious and life-threatening conditions for which there is no satisfactory alternative treatment. Rifabutin is newly available for use under Treatment IND as prophylaxis against disseminated mycobacterium avium complex (MAC) infection. Rifabutin, a broad-spectrum, antibacterial analog of rifampicin, is to be used for MAC prophylaxis in HIV-positive patients 12 years of age or older with CD4 lymphocyte counts of 200/μL (0.20×10 9 /L) or below. It is administered orally at 300 mg a day. Rifabutin is the first drug for which there are data from controlled trials that may indicate effectiveness in delaying or preventing MAC infections in