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Biomedical subjects

P Bacchetti

Publications and source records attributed to P Bacchetti.

At least 73 records · Page 4Linked to original sources
PubMed1994

The impact of lengthening AIDS reporting delays and uncertainty about underreporting on incidence trends and projections.

This article extends existing methods for estimating reporting delays to allow nonparametric estimation of how delays are changing over time. Also implemented are refinements to estimate calendar month effects and to improve the accuracy of trend estimates by focusing on delays of > 6 months. Applying the method to 1987-definition adult and adolescent AIDS cases reported by June 1992 shows strong evidence for a nonlinear trend toward longer delays among cases diagnosed more recently and for slower reporting of cases diagnosed in January and June of each year. Combining estimated reporting delay corrections with the possibility of increasing underreporting produces a 14-16% higher estimated incidence by December 1991 and a 19-24% higher projected incidence by December 1993 than using the delay corrections provided with the public information AIDS data and assuming constant underreporting rates.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Different AIDS incubation periods and their impacts on reconstructing human immunodeficiency virus epidemics and projecting AIDS incidence.

The objective of this study was to investigate heterogeneity in incubation distributions in different cohorts and to assess the sensitivity of back-calculated infection rates to different assumptions about incubation times from human immunodeficiency virus (HIV) infection to AIDS diagnosis. Incubation distributions were estimated by using data from three different cohort studies. These and one other published incubation model were used as inputs for a back-calculation procedure that reconstructed smooth HIV-infection rates from AIDS incidence among adults in the United States, allowing for changes over time in incubation. Incubation estimates from the different cohorts differed substantially. The cumulative HIV incidence estimates that result from using the different incubations are very different, but the back-calculated models all produce good fits to the observed diagnosis counts. We conclude that systematic differences in incubation times of different groups add substantially to the uncertainty inherent in using the back-calculation method to reconstruct HIV epidemics and project future numbers of AIDS cases.

Acquired Immunodeficiency Syndrome↗
PubMed1992

An annotated bibliography of methods for analysing correlated categorical data.

This paper provides an annotated bibliography of over 100 articles concerning methods for analysing correlated categorical response data. Most of the papers listed here concern categorical regression models and estimation, with particular emphasis on binary responses. The papers are classified by several characteristics which group them according to common themes. The bibliography serves as a reference of methods for analysts of correlated categorical data, as well as for persons interested in methodologic work in this active area of statistical research.

Clinical Trials as Topic↗
PubMed1992

Early predictors of survival in symptomatic HIV-infected persons treated with high-dose zidovudine.

The survival times of 246 patients treated with high-dose zidovudine beginning in 1986 were obtained through November 1988. We analyzed clinical and laboratory predictors of survival as measured before initiation of therapy and during the first 32 weeks of therapy. In a multivariate proportional-hazards model, we found significant independent predictive abilities for four pretherapy measurements (AIDS versus ARC diagnosis, Karnofsky performance score, age, and hemoglobin) and four measurements made during therapy (change in log CD4 lymphocyte count from pretherapy to week 24, CD8 lymphocyte count at week 24, rate of decline of hemoglobin over the first 3 months of therapy, and rate of decline in white blood count over the first 6 months of therapy). The presence of three predictors measured during therapy that are statistically significant when controlled for changes in CD4 count suggests that the use of other measures in addition to CD4 counts may substantially improve the prediction of long-term survival based on early response of surrogate markers to therapy.

Drug Administration Schedule↗
PubMed1991

Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine.

OBJECTIVE: To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of beta 2 microglobulin, neopterin, or HIV p24 antigen or antibody are correlated with survival in patients with AIDS or AIDS related complex. DESIGN: Retrospective study of changes in laboratory markers and survival. SETTING: Multicentre trial at university hospital clinics. SUBJECTS: 90 Patients with AIDS or AIDS related complex. INTERVENTION: Patients started zidovudine 200 mg orally every four hours. Fifty six of the patients died a median 17 months after starting zidovudine; the remaining 34 patients were followed up for a median 25.5 months. MAIN OUTCOME MEASURES: Changes in CD4+ lymphocyte count and serum concentrations of p24 antigen and antibody, beta 2 microglobulin, and neopterin; survival of the patient. RESULTS: The pretreatment characteristics that independently predicted poor survival were determined using a multivariate proportional hazards model: a diagnosis of AIDS (v AIDS related complex), age over 45 years, and the logarithm of serum neopterin concentration. When these baseline characteristics were controlled for the logarithm of CD4+ lymphocyte count at weeks 8-12 of treatment (p = 0.007) and an increase in serum beta 2 microglobulin concentration at weeks 8-12 (p = 0.05) also independently correlated with survival. In the 38 patients with a better pretreatment prognosis, 24 month survival estimated by the product-limit method was 88% for those with a good response on both surrogate markers during early treatment compared with only 50% for those with a poor response on either marker. In the 38 with a worse pretreatment prognosis, 24 month survival was estimated to be 49% for those with a good response on both surrogate markers compared with only 18% for those with a poor response on either. CONCLUSION: These data suggest that CD4+ lymphocyte count at 8-12 weeks and, perhaps, change in serum beta 2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.

AIDS-Related Complex↗
PubMed1991

Human T cell lymphotropic virus types I and II in intravenous drug users in San Francisco: risk factors associated with seropositivity.

Serologic assays for human T cell lymphotropic virus types I and II (HTLV I/II) infection were done in 676 intravenous drug users (IVDUs) in San Francisco between 1985 and 1987: 150 in 1985, 44 in 1986, and 482 in 1987. All sera were tested by Western blot, ELISA, and p24 RIA. A total of 111 participants were seropositive in a minimum of two assays. Duration of intravenous heroin use was strongly associated with the risk of HTLV I/II seropositivity: greater than or equal to 21 years odds ratio, 6.1 (95% confidence interval [CI], 2.2-17.5), compared with less than 10 years of heroin use. Additional independent risk factors included black or Hispanic race, female sex, and the use of drugs in a shooting gallery. Coinfection of HTLV I/II and human immunodeficiency virus was less frequent than expected by chance (P less than .02). Longitudinal specimens were available in 154 participants. The age- and race-adjusted seroconversion rate was 3.4% (95% CI, 1.3-8.9) per person per year. Of the 349 homosexual men tested, none were HTLV I/II-seropositive.

Adult↗
PubMed1991

Immune activation markers and AIDS prognosis.

Four assays for serum levels of cellular products of immune activation were examined as prognostic markers for AIDS in a prospective study of asymptomatic HIV-seropositive homosexual men. Baseline serum values of beta 2-microglobulin (beta 2M), neopterin, soluble CD8 (sCD8), and soluble interleukin-2 receptor (sIL-2R) for 185 men were examined univariately and multivariately as predictors of AIDS during 36 months of follow-up. Thirty-three cases of AIDS (18%) were diagnosed during the follow-up period. All four assays correlated highly with each other (r = 0.48-0.63), and all four were good univariate predictors of AIDS and comparable to CD4 lymphocyte count. beta 2M, neopterin, and sCD8 predicted AIDS independently of both CD4 count and HIV p24 antigen or p24 antibody in multivariate analysis. Within the range of CD4 count 200-499 x 10(6) cells/l, an immune activation marker used in combination with an assay for p24 antigen identifies those at 3-6% risk of AIDS over 36 months (low risk on both assays) and those at 63-86% risk (high risk on both assays). These results can be used to guide physicians and patients making decisions about treating asymptomatic HIV infection with zidovudine in individuals with CD4 lymphocyte count of 200-499 x 10(6) cells/l.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Survival of patients with AIDS and cytomegalovirus disease treated with ganciclovir or foscarnet.

We reviewed the hospital charts of 168 patients with AIDS and cytomegalovirus (CMV) disease diagnosed at San Francisco General Hospital between July 1985 and October 1989. One hundred and thirty-three patients had CMV retinitis, 33 had CMV gastrointestinal disease, and two had CMV lung disease. We found a trend towards longer survival from time of CMV disease diagnosis in patients with more recent dates of diagnosis. The median survival of patients diagnosed with CMV disease prior to 30 September 1987 was 4 months, compared with 9 months for patients diagnosed after 30 September 1987 (P = 0.001). The relative hazard of death for patients with CMV retinitis who were initially treated with foscarnet was not significantly reduced compared to those initially treated with ganciclovir. Even after controlling for age at time of CMV diagnosis, time from index AIDS diagnosis, hemoglobin, absolute lymphocyte count, absolute neutrophil count and concurrent zidovudine therapy, the relative hazard for foscarnet-treated patients compared with ganciclovir-treated patients was 1.0 (95% confidence interval, 0.5-1.8).

Acquired Immunodeficiency Syndrome↗
PubMed1991

Nonparametric estimation of the incubation period of AIDS based on a prevalent cohort with unknown infection times.

Estimation of the incubation period distribution of human immunodeficiency virus based on prevalent cohorts of subjects, already infected at the time of recruitment, is complicated by the absence of information on the original times of infection. Here, we overcome this difficulty by using a prior distribution for the infection times, based on external data. Our estimate is nonparametric, but uses smoothness assumptions to avoid instability. The method is illustrated on two prevalent cohorts from San Francisco, separately and combined. The estimates produced agree with other published estimates of the incubation period distribution.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Results of a one year longitudinal study of HIV antibody test notification from the San Francisco General Hospital cohort.

We examined the psychological impact of HIV antibody testing in 107 homosexual men in San Francisco. Seventy-eight percent of the seropositives but only 43% of the seronegatives correctly anticipated their results. Twelve months after notification (but not earlier), notified seropositives reported significantly greater increases in total distress than nonnotified controls. However, notified seronegatives demonstrated significantly lower levels of hopelessness than nonnotified controls at every follow-up assessment. Thus, knowledge of HIV antibody status appears to dispel a sense of gloom in persons who incorrectly believe themselves to be infected with HIV, but does not appear to induce significant distress in those whose expectation of a positive result is confirmed. Both groups reported lower distress than men with ARC or AIDS, suggesting that distress was related more to symptomatology than knowing antibody status. These results suggest the benefits of HIV testing for the considerable proportion of seronegative subjects believing themselves to be seropositive and should be weighted against the more limited induction of distress in seropositives who receive confirmation of their test result expectation. The benefits of testing are also supported by increasing knowledge of the usefulness of early intervention in HIV disease.

AIDS Serodiagnosis↗
PubMed1990

Sensitivity of treponemal tests for detecting prior treated syphilis during human immunodeficiency virus infection.

To evaluate the sensitivity of treponemal tests as a marker of prior syphilis in individuals with human immunodeficiency virus (HIV) infection, the syphilis serology of 109 homosexual men with a documented history of treated syphilis was compared with records of prior results and confirmed on stored serum samples. None of the HIV-seronegative individuals lost reactivity to a treponemal test, whereas 7% of the seropositive asymptomatic individuals and 38% of those with symptomatic HIV infection had loss of reactivity. Symptomatic HIV infection was associated with loss of reactivity, as a T4 lymphocyte count less than 200 X 10(6)/1, a T4-to-T8 ratio less than 0.6, a single prior episode of syphilis, and a low VDRL titer at the time of the last documented episode of syphilis. Although no conclusions can be drawn about the sensitivity of treponemal tests in patients with active syphilis and HIV infection, these data suggest that treponemal tests may not identify those previously infected with Treponema pallidum.

Adult↗
PubMed1989

Incubation period of AIDS in San Francisco.

In a closed population, the distribution of AIDS diagnoses over time is the convolution of the distributions of human immunodeficiency virus (HIV) infections and the incubation period. This has motivated estimates of the infection distribution, assuming known diagnosis and incubation distributions, but the usefulness of this method is limited by uncertainty about incubation. The large amount of information on the distribution of HIV infections in San Francisco's gay community suggests the opposite approach--estimating the incubation distribution, assuming known infection and diagnosis distributions. A non-parametric implementation of this strategy produced an estimate with a median at 9.8 years, increasing hazard rates, and less uncertainty than previous estimates.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Cocaine use and HIV infection in intravenous drug users in San Francisco.

We assessed risk factors for human immunodeficiency virus (HIV) infection in 633 heterosexual intravenous drug users. The HIV seroprevalence was 26% in blacks, 10% in Hispanics, and 6% in whites. Intravenous cocaine use significantly increased the risk of HIV infection, with a seroprevalence of 35% in daily cocaine users (odds ratio, 6.4; 95% confidence interval, 3.0 to 13.3). Black subjects were more likely to use cocaine regularly. Drug use in shooting galleries and sharing of drug injection equipment were also associated with HIV infection and were more common in cocaine users. By multivariate analysis, black race, daily cocaine injection by blacks and Hispanics, all other cocaine injection, heavy use prior to entry into methadone treatment by blacks, and use of drugs in shooting galleries were independent predictors of HIV infection. Methadone therapy was associated with substantial reductions in heroin use and some reduction in cocaine use, but 24% of cocaine users receiving methadone began or increased cocaine injection after entry into treatment.

Black or African American↗
PubMed1989

Lymphocyte subset analysis to predict progression to AIDS in a cohort of homosexual men in San Francisco.

A group of 10 leukocyte and lymphocyte subsets were measured by simultaneous dual immunofluorescence and flow cytometry in a group of homosexual men from the San Francisco General cohort. Absolute numbers and percentages of lymphocytes were determined in 30 individuals who progressed to AIDS and 29 who did not over a 44-month period at annual intervals. At entry into the study, all subjects were asymptomatic, HIV seropositive, and had multiple changes in lymphocyte subsets compared to HIV-negative controls. In progressors, large changes occurred from the first visit to the last visit before progression in both absolute numbers and percentages of CD4 cells. The percentage of HLA-DR-bearing CD8 cells also increased. We utilized a proportional hazards model to assign a predictive value for progression to AIDS to lymphocyte subsets in both univariate and multivariate tests. Increased DR-positive CD8 cells, decreased CD4 cells, and increased CD8-positive, Leu 7-positive cells independently predicted progression to AIDS at P less than 0.006 (relative hazard 5.8-4.0). In a multivariate model, the most useful tests were either increased numbers or percentages of DR-positive CD8 cells. These data suggest parsimonious approaches to following HIV-positive individuals and further support the possibility of autoreactive T cells in the pathogenesis of HIV-associated diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Low dose intermittent 5-fluorouracil, epirubicin and cyclophosphamide (FEC) in poor risk patients with advanced transitional cell bladder cancer: a pilot study.

Fifteen patients with locally advanced or metastatic bladder carcinoma and with cardiac and/or renal impairment were treated with a combination of 5-fluorouracil, 400 mg/m2, epirubicin, 40 mg/m2, and cyclophosphamide, 400 mg/m2. No complete or partial remissions were observed among the 14 evaluable patients. The toxicity level was very low. We are now trying to "tailor" platinum-based combinations to renal function.

Aged↗
PubMed1989

Serum beta 2-microglobulin decreases in patients with AIDS or ARC treated with azidothymidine.

Abnormally elevated serum beta 2-microglobulin has been associated with progression of human immunodeficiency virus (HIV) disease and could reflect in vivo HIV activity. We prospectively studied the effect of azidothymidine therapy on serum beta 2-microglobulin concentration in 41 patients with AIDS or AIDS-related complex. Median beta 2-microglobulin concentration decreased from 4.02 mg/L before therapy to 3.73 mg/L at week 24 of therapy (P = .016). Individual changes in beta 2-microglobulin during azidothymidine therapy correlated with changes in serum HIV p24 antigen (Spearman, r = .42, P = .007). Also, in a randomized placebo-controlled study, median beta 2-microglobulin concentration decreased after 16 w of therapy in 5 azidothymidine-treated patients compared with levels in 7 placebo-treated controls (P = .05). Serum beta 2-microglobulin appears to be a sensitive marker for in vivo antiretroviral drug activity and may be a better marker than serum p24 antigen for early intervention trials involving antiretroviral agents.

AIDS-Related Complex↗