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Biomedical subjects

M Schechter

Publications and source records attributed to M Schechter.

At least 19 recordsLinked to original sources
PubMed2000

Effect of antiretroviral therapy on HIV shedding in semen.

BACKGROUND: The effect of antiretroviral therapy on seminal HIV shedding in the community remains unknown. OBJECTIVE: To evaluate the effect of antiretroviral therapy on HIV shedding in semen. DESIGN: Prospective cohort study. SETTING: University hospital in Rio de Janeiro, Brazil. PATIENTS: 93 HIV-infected men. INTERVENTION: Antiretroviral therapy as prescribed by each patient's physician. MEASUREMENT: HIV RNA in semen and blood plasma before and after introduction of therapy. RESULTS: At baseline, HIV RNA was detected in 69 semen samples (74%) and 89 blood samples (96%). Six months after introduction of therapy, HIV RNA was detected in 29 semen samples (33%) and 33 blood samples (38%). The mean reduction in levels of HIV RNA in semen at 6 months was 1.65 log10 units. CONCLUSIONS: Antiretroviral therapy reduces shedding of HIV in semen, which probably in tum reduces HIV transmissibility. However, a substantial proportion of patients may still be infectious and may have drug-resistant strains of the virus.

Adult↗
PubMed2000

HIV disease progression and V3 serotypes in Brazil: is B different from B-Br?

HIV-1 serotype B-Br (GWGR) is rare in the United States but predominates in Brazil. Differences in prognosis for patients infected with serotype B-Br or serotype B (GPGR) have not been addressed previously. In this prospective cohort study, we compared the rate of disease progression between patients infected with the HIV-1 V3 serotype B or B-Br in Brazil. Progression to AIDS or death was studied by the Kaplan-Meier and Cox proportional hazard methods. Among 445 HIV-infected patients who were tested with a specific enzyme immune assay, 204 (46%) had serotype B-Br infection and 127 (28%) had serotype B infection. Both groups were similar with regard to baseline CD4+ cell count, serum HIV RNA viral load, initial clinical stage, and the proportions who were treated with antiretroviral drugs. Patients with serotype B infection were significantly younger (p = 0.005) and tended to report homosexual behavior more frequently (p = 0.08). Mean follow-up was 30 +/- 13.5 months. During the study period, 41 (32%) patients infected with serotype B and 44 (22%) infected with serotype B-Br developed AIDS (p = 0.03). In a regression model adjusted for age and risk factor for HIV infection, progression to AIDS was faster in patients infected with serotype B (hazard ratio [HR] 1.59; 95% CI, 1.03-2.43; p = 0.03). A similar trend was observed in a model that considered AIDS or death as the outcome (HR, 1.43; 95% CI, 0.95-2.0; p = 0.09). These results suggest that patients infected with closely related HIV-1 serotypes may differ in the rate of progression to AIDS and indicate that serotype should be taken into account in HIV vaccine studies in Brazil.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Identification of a high-risk heterosexual population for HIV prevention trials in Rio de Janeiro, Brazil. Projeto Praço Onze Study Group.

The study of interventions to prevent HIV transmission requires access to populations with a high rate of HIV transmission. We estimated HIV incidence among heterosexual males and females who were seen at an HIV testing site in Rio de Janeiro, Brazil. Stored sera from individuals who visited the site between March and December 1998 were analyzed using the sensitive/less sensitive (S/LS) assay and a chart abstraction was performed. During the study period, 6353 serum samples were tested. Of those tested, 1203 were found to be HIV-seropositive or indeterminate, of which 1050 (87%) remained available for further testing. In addition, 84 serum samples, representing 63 adults, were found to produce results suggesting early HIV infection. Of these, 14 were heterosexual and female (median age, 38 years), and 19 were heterosexual and male (median age, 25 years). The estimated HIV seroincidence was 1.9 (95% confidence limits (CL), 0.9%-3.9%) and 2.8 (95% CL, 1.4%-5.3%) per 100 person-years among heterosexual women and men, respectively. A survey on willingness to participate in future placebo-controlled HIV vaccine trials in this population indicated that 54.5% and 53.9% of heterosexual women and men, respectively, indicated that they would definitely be willing to participate. We have identified a heterosexual population in Rio de Janeiro with a high rate of HIV transmission willing to participate in placebo-controlled vaccine trials. This study demonstrates the usefulness of the newly described S/LS assay, which allows one to estimate HIV incidence from single serum specimens.

Adult↗
PubMed2000

Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group.

CONTEXT: Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed. OBJECTIVE: To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection. DESIGN: Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997. SETTING: Outpatient clinics in the United States, Mexico, Haiti, and Brazil. PARTICIPANTS: A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result. INTERVENTIONS: Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791). MAIN OUTCOME MEASURES: The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group. RESULTS: Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P = .28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01). Neither regimen appeared to lead to the development of drug-resistant tuberculosis. CONCLUSIONS: Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs.

AIDS-Related Opportunistic Infections↗
PubMed2000

Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel.

OBJECTIVE: To update recommendations for antiretroviral therapy for adult human immunodeficiency virus type 1 (HIV-1) infection, based on new information and drugs that are available. PARTICIPANTS: A 17-member international physician panel with antiretroviral research and HIV patient care experience initially convened by the International AIDS Society-USA in December 1995. EVIDENCE: Available clinical and basic science data including phase 3 controlled trials; data on clinical, virologic, and immunologic end points; research conference reports; HIV pathogenesis data; and panel expert opinion. Recommendations were limited to therapies available (US Food and Drug Administration approved) in 1999. CONSENSUS PROCESS: The panel assesses new research reports and interim results and regularly meets to consider how the new data affect therapy recommendations. Recommendations are updated via full-panel consensus. Guidelines are presented as recommendations if the supporting evidence warrants routine use in the particular situation and as considerations if data are preliminary or incomplete but suggestive. CONCLUSIONS: The availability of new antiretroviral drugs has expanded treatment choices. The importance of adherence, emerging long-term complications of therapy, recognition and management of antiretroviral failure, and new monitoring tools are addressed. Optimal care requires individualized management and ongoing attention to relevant scientific and clinical information in the field.

Adult↗
PubMed1999

Incident HIV infection in a high-risk, homosexual, male cohort in Rio de Janeiro, Brazil.

An HIV seroincidence study was conducted to identify a high-risk population for HIV prevention trials. Inclusion criteria were male gender, homosexual behavior, age between 18 and 50 years, and negative HIV serostatus; 862 study subjects were screened and 753 were enrolled and observed during follow-up for a mean of 1.5 years. In this population, 34 people had HIV seroconversions for an overall annual seroincidence of 3.1% (95% confidence interval [CI], 2.1%-4.1%). Among study subjects <20 years old, annual incidence was 8.4% (95% CI, 1.7%-15%). Independent risk factors for seroconversion were age <25 years (p = .01), hepatitis B core antibody seropositivity (p > .01), sex at first encounter in the preceding 6 months (p = .11), and a history of gonorrhea or condyloma in the 6 months before seroconversion (p = .04 and p = .08, respectively). At enrollment, 85% of the eventual seroconverters said they would participate in a vaccine trial; all agreed to participate when told there would be a placebo arm. Follow-up rates were 97%, 91%, and 88% at 6, 12, and 18 months, respectively. The HIV-1 subtype was B for each of the first 17 seroconverters. These data demonstrate the suitability of this cohort for HIV prevention trials, based on high HIV incidence and retention rates, and a willingness to participate in such trials.

AIDS Vaccines↗
PubMed1999

Protease inhibitors as initial therapy for individuals with an intermediate risk of HIV disease progression: is more necessarily better?

OBJECTIVE: To compare three possible therapeutic strategies for the treatment of patients with an intermediate risk of HIV disease progression. DESIGN: Mathematical modeling based on assumptions derived from published data. METHODS: A parametric survival model was fitted to empirical data to describe the survival trajectory of untreated individuals. It was assumed that successful treatment decreases the risk of disease progression curing the first year after its introduction by a constant that is dependent on the magnitude of the initial drop in HIV viral load. Thereafter, individual members of the treatment cohort follow different pathways, depending on the duration of the initial response or, in case of virologic failure, the response to a new drug regimen. RESULTS: Sub-groups of patients starting therapy with two nucleoside reverse transcriptase inhibitors (NRTI) or two NRTI and a protease inhibitor had the highest instantaneous risk of disease progression at the end of the 5-year follow-up period. Patients who started therapy with two NRTI and a non-NRTI had the lowest likelihood of progression to AIDS or death at 5 years of follow-up. This is because, in the case of the subgroup whose initial treatment included a protease inhibitor, failure rates due to non-adherence to therapy are high and response to salvage therapy is limited by past protease inhibitor experience. CONCLUSIONS: Despite the superior virologic potency of the protease inhibitor-containing regimens, in this analysis other strategies performed equally well or even better. In the absence of solid empirical data and until the advent of antiretroviral regimens that are shown to be safe, simple to take, and maximally suppress viral load, caution may be required in selecting the long-term therapy for patients with less advanced HIV disease.

Anti-HIV Agents↗
PubMed1999

Genetic variation and susceptibilities to protease inhibitors among subtype B and F isolates in Brazil.

The genetic variation of the human immunodeficiency virus type 1 (HIV-1) protease gene (prt) permits the classification of HIV-1 strains into five distinct protease subtypes, which follow the gag subtyping patterns. The susceptibilities of non-B-subtype strains to protease inhibitors (PIs) and other antiretroviral drugs remain largely unknown. Subtype F is the main non-B strain contributing to the Brazilian epidemic, accounting for 15 to 20% of these infections. In this work, we report the findings on 81 isolates from PI-naive Brazilian patients collected between 1993 and 1997. In addition, the relevant PI resistance mutations and their phenotypes were determined in vitro for 15 of these patients (B = 9 and F = 6). Among these, the subtype F samples evidenced high sensitivities in vitro to ritonavir and indinavir, with MICs at which 50 and 90% of the isolates are inhibited similar to those of both the Brazilian and the U.S. subtype B isolates. Analysis of the 81 Brazilian prt sequences demonstrated that the subtype F consensus sequence differs from the U.S. and Brazilian subtype B consensus in eight positions (I15V, E35D, M36I, R41K, R57K, Q61N, L63P, and L89M). The frequency of critical PI resistance substitutions (amino acid changes D30N, V82A/F/T, I84V, N88D, and L90M) among Brazilian isolates is very low (mean, 2.5%), and the associated secondary substitutions (amino acid positions 10L, 20K, 36M, 46M, 48G, 54I, 63P, 71A, and 77A) are infrequent. These observations document the relative rarity of resistance to PIs in the treatment of patients infected with HIV-1 subtype F in South America.

Amino Acid Sequence↗
PubMed1998

Gender and survival after AIDS in Rio de Janeiro, Brazil.

The relation between gender and survival after a diagnosis of AIDS was studied in a cohort of patients with HIV infection in Rio de Janeiro, Brazil. During the study period, 124 of 617 patients (20%) developed AIDS. Of this group, 91 patients were men and 33 were women. There were no gender related differences regarding the access to antiretroviral therapy or to prophylaxis for Pneumocystis carinii pneumonia. Survival was shorter among women (hazard ratio [HR] = 4.43; p < .001) after adjustment for age and AIDS-defining condition. Adjusting for CD4+ and CD8+ counts reduced the difference between genders (HR = 3.33; p = .017). These results suggest that survival after an AIDS diagnosis may be shorter among women than men in Brazil. Further studies are needed to determine the factors that may be negatively influencing the prognosis of women with AIDS in Brazil.

AIDS-Related Opportunistic Infections↗
PubMed1998

Comparison of the prevalence of antibodies to human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) in Brazil and Colorado.

The prevalence of human herpesvirus 8 (HHV-8; Kaposi's sarcoma [KS] herpesvirus) infection was determined by IFA in 297 persons living in Brazil and Colorado. The prevalence of antibody to HHV-8 in human immunodeficiency virus (HIV) type 1-seropositive gay men with and without KS was similar in Brazil and Colorado. In Brazil, the prevalence of HHV-8 antibody was significantly greater in HIV-1-seronegative gay men than in HIV-1-seronegative male intravenous drug users. HHV-8-seropositive Brazilian gay men who had a clinical diagnosis of KS or who were infected with HIV-1 had significantly higher titers of HHV-8 antibody than did HHV-8-seropositive, HIV-1-seronegative Brazilian gay men. These findings provide further support for the association between HHV-8 infection and KS and suggest that, as in the United States, HHV-8 infection is transmitted sexually in Brazil.

Adolescent↗
PubMed1998

Horizontal and vertical transmission of human immunodeficiency virus type 1 dual infections caused by viruses of subtypes B and C.

This article describes a case of horizontal (heterosexual) and subsequent vertical (mother to infant) transmission of 2 human immunodeficiency viruses type 1 (HIV-1) subtypes. Dual infection in a husband, his wife, and their child was initially detected by use of a restriction fragment length polymorphism assay of the proviral protease in peripheral blood mononuclear cells. The simultaneous presence of highly similar sets of HIV-1 subtypes B and C infecting the 3 family members was confirmed by DNA sequence analysis of pol, gag, and env genes. These data, together with available epidemiologic information, may indicate that the husband's high-risk sexual behavior was the source of dual infections. Because his wife did not report such activities, it was likely that he passed HIV-1 strains to his spouse, who subsequently transmitted them to their child.

Adult↗
PubMed1998

Upstairs downstairs: vertical integration of a pediatric service.

BACKGROUND: The combined effects of recent changes in health care financing and training priorities have compelled academic medical centers to develop innovative structures to maintain service commitments yet conform to health care marketplace demands. In 1992, a municipal hospital in the Bronx, New York, affiliated with a major academic medical center reorganized its pediatric service into a vertically integrated system of four interdependent practice teams that provided comprehensive care in the ambulatory as well as inpatient settings. One of the goals of the new system was to conserve inpatient resources. OBJECTIVE: To describe the development of a new vertically integrated pediatric service at an inner-city municipal hospital and to test whether its adoption was associated with the use of fewer inpatient resources. DESIGN: A descriptive analysis of the rationale, goals, implementation strategies, and structure of the vertically integrated pediatric service combined with a before-and-after comparison of in-hospital resource consumption. METHODS: A before-and-after comparison was conducted for two periods: the period before vertical integration, from January 1989 to December 1991, and the period after the adoption of vertical integration, from July 1992 to December 1994. Four measures of inpatient resource use were compared after adjustment for case mix index: mean certified length of stay per case, mean number of radiologic tests per case, mean number of ancillary tests per case, and mean number of laboratory tests per case. Difference-in-differences-in-differences estimators were used to control for institution-wide trends throughout the time period and regional trends in inpatient pediatric practice occurring across institutions. Results. In 1992, the Department of Pediatrics at the Albert Einstein College of Medicine reorganized the pediatric service at Jacobi Medical Center, one of its principal municipal hospital affiliates, into a vertically integrated pediatric service that combines ambulatory and inpatient activities into four interdependent practice teams composed of attending pediatricians, allied health professionals, house officers, and social workers. The new vertically integrated service was designed to improve continuity of care for patients, provide a model of practice for professional trainees, conserve scarce resources, and create a clinical research infrastructure. The vertically integrated pediatric service augmented the role of attending pediatricians, extended the use of allied health professionals from the ambulatory to the inpatient sites, established interdisciplinary practice teams that unified the care of pediatric patients and their families, and used less inpatient resources. Controlling for trends within the study institution and trends in the practice of pediatrics across institutions throughout the time period, the vertical integration was associated with a decline in 0.6 days per case, the use of 0.62 fewer radiologic tests per case, 0.21 fewer ancillary tests per case, and 2.68 fewer laboratory tests per case. CONCLUSIONS: We conclude that vertical integration of a pediatric service at an inner-city municipal hospital is achievable; conveys advantages of improved continuity of care, enhanced opportunities for primary care training, and increased participation of senior clinicians; and has the potential to conserve significant amounts of inpatient resources.

Academic Medical Centers↗
PubMed1997

HIV viral load and CD4+ lymphocyte counts in subjects coinfected with HTLV-I and HIV-1.

Reports indicate that there is a dissociation between markers of HIV disease progression and clinical stage among subjects coinfected with human T-cell lymphotropic virus type I (HTLV-I) and HIV. HTLV-I coinfection does not appear to affect HIV viral load, currently considered to be the best marker of HIV disease progression. We measured HIV RNA levels in stored serum samples from 23 subjects with coinfection and 92 subjects with HIV single infection and examined the correlation with the CD4+ lymphocyte count. Subjects were recruited from an ongoing HIV cohort study in Rio de Janeiro, Brazil. In both groups, CD4+ lymphocyte counts declined with increasing levels of HIV RNA. In a linear regression analysis adjusting for HIV RNA serum level, coinfected individuals had an estimated 78% higher CD4+ lymphocyte count than those with single infection. Simultaneous adjustment for beta2-microglobulin level increased the difference, with coinfected individuals having 146% (p = 0.005, 95% CI: 32% to 359%) higher CD4+ counts. These data suggest that the higher CD4+ lymphocyte counts associated with coinfection do not provide immunologic benefit and may reflect HTLV-I-associated nonspecific lymphocyte proliferation. The results of this and other studies suggest that the CD4+ count cutoff values used in making clinical decisions in HIV infection may not be appropriate in coinfection. As with HIV single infection, HIV virus load may be the optimal surrogate marker for subjects with coinfection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Human T cell lymphotropic virus type I does not increase human immunodeficiency virus viral load in vivo.

Human T lymphotropic virus type I (HTLV-I) can increase human immunodeficiency virus (HIV) replication in vitro, and several studies suggest that HTLV-I accelerates the progression of HIV infection. To determine whether HTLV-I enhances HIV replication in vivo, a case-control study was done of serum HIV viral load, using polymerase chain reaction, in 23 subjects with HTLV-I/HIV coinfection and 92 control subjects with HIV single infection. The geometric mean serum RNA level was 11,482 copies/mL in the coinfected group and 13,804 in the single-infection group (P = .57), a result that did not change after adjustment for zidovudine use and CD4 cell count. Among subjects with advanced HIV infection, there was a trend toward higher viral load among singly infected subjects. HTLV-I did not appear to increase HIV plasma RNA levels in subjects with coinfection. These results do not provide a biologic basis for the hypothesis that HTLV-I accelerates the course of HIV infection.

Adult↗
PubMed1997

Detection of genetically diverse human immunodeficiency virus type 1 group M and O isolates by PCR.

A panel of 136 genetically diverse group M and 5 group O adult isolates from outside the United States and Europe were evaluated by PCR with the Roche AMPLICOR HIV-1 test, a modified version of the AMPLICOR HIV-1 test, and a new primer pair/probe system. Detection of some of these isolates was less efficient with the AMPLICOR HIV-1 test; however, the assay was significantly improved by reducing the sample input and lowering the annealing temperature. The new primer pair/probe set detected 140 of 141 isolates, including the 5 group O isolates that were not detected with either of the AMPLICOR HIV-1 test formats.

Adult↗