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Biomedical subjects

F M Hecht

Publications and source records attributed to F M Hecht.

At least 19 recordsLinked to original sources
PubMed2005

Longitudinal analysis of B cell repertoire and antibody gene rearrangements during early HIV infection.

In chronically HIV infected individuals, a number of functional B cell abnormalities have been described. However, the immediate changes that occur in the B cell compartment following viral exposure and how they affect the long-term course of infection are not well understood. We report the longitudinal analysis of B cell repertoires during early infection in untreated and treated individuals receiving highly active antiretroviral therapy (HAART). Analysis was based on IgG heavy chain gene utilization and CDR3 length measurement and relationship with CD4/CD8 counts, viral load, and total serum IgG, and anti-HIV antibodies levels. Repertoires were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. The findings indicate a stable peripheral B cell repertoire during the first 72 weeks following infection, particularly in the HAART treated patients. A modest association between B cell repertoire integrity and viremia levels as well as treatment was detected.

Adult↗
PubMed2004

Effect of IL-2 therapy on CD8+ cell noncytotoxic anti-HIV response during primary HIV-1 infection.

Early treatment intervention during human immunodeficiency virus (HIV) infection is a strategy aimed to preserve and/or enhance the developing anti-HIV immune responses. We report the effect of highly active antiretroviral therapy (HAART) combined with intermittent subcutaneous doses of Interleukin 2 (IL-2) on CD8(+) cell noncytotoxic anti-HIV responses (CNAR), as well as on viral loads and CD4(+) cell/CD8(+) cell numbers in subjects with primary HIV-1 infection. Twenty-four patients received HAART, 24 received a combination of HAART plus IL-2, and 12 elected no-therapy. In comparison to HAART alone, IL-2 treatment led to significant increases in CD4(+) cell numbers through week 48 of the study. No effect was observed on viral loads or the CD8(+) cell population. The first cycle of IL-2 enhanced CNAR; later cycles showed no substantial effect. This study suggests that HAART combined with IL-2 could provide an immunologic benefit in the treatment of early HIV infection.

Adult↗
PubMed2002

What happened to home HIV test collection kits? Intent to use kits, actual use, and barriers to use among persons at risk for HIV infection.

Through sequential cross-sectional surveys, we examined intent to use home HIV test collection kits, actual use and barriers to use among persons at high risk for HIV infection. Interest in kits was assessed in the 1995-96 HIV Testing Survey (HITS, n=1683). Kit use, knowledge of kits and barriers to use were assessed in the 1998-99 HITS (n=1788), after kits had become widely available. When asked to choose among future testing options, 19% of 1995-96 participants intended to use kits. Untested participants were more likely than previously tested HIV-negative participants to choose kits for their next HIV test (p < 0.001). Among 1998-99 participants, only 24 (1%) had used kits; 46% had never heard of kits. Predictors of not knowing about kits included never having been HIV tested and black or Latino race. Common reasons for not using kits among participants aware of home test kits were concerns about accuracy, lack of in-person counselling and cost. Despite high rates of anticipated use, kits have had minimal impact on the testing behaviour of persons at high risk for HIV infection. Increasing awareness of kits, reducing price and addressing concerns about kit testing procedures may increase kit use, leading to more HIV testing by at-risk individuals.

Cross-Sectional Studies↗
PubMed2001

Provider assessment of adherence to HIV antiretroviral therapy.

BACKGROUND: Adherence assessment is an essential component of monitoring HIV antiretroviral therapy. Prior studies suggest that medical providers frequently estimate individual patient adherence inaccurately. OBJECTIVE: We compared provider estimates of nonadherence to antiretroviral therapy with unannounced pill counts and structured patient interviews to determine the accuracy of adherence information obtained by providers and patients. DESIGN, SETTING, AND PARTICIPANTS: Comparison of three adherence measures in homeless or marginally housed persons receiving HIV antiretroviral therapy (n = 45) and their providers (n = 35). MEASUREMENTS: Provider estimate of percentage of pills taken; three successive patient structured reports of number of doses missed in the last 3 days; and three successive unannounced pill counts. RESULTS: 13% (95% confidence interval [CI], 4%-22%) of patients were not following their regimen as directed. Provider-adherence estimate explained only 26% (95% CI, 6%-47%) of the variation in pill count adherence, whereas patient report explained 72% (95% CI, 52%-96%). The sensitivity and specificity of provider estimates of nonadherence, defined as <80% of pills taken by pill count, were 40% and 85%, respectively. The sensitivity and specificity of patient interview were 72% and 95%, respectively. CONCLUSIONS: Provider estimate of adherence was inaccurate whereas structured patient report was more closely related to pill count. Structured assessment over several short intervals may improve accuracy of adherence assessment in clinical practice.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection.

Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection.

Acute Disease↗
PubMed2001

Reduction in CD8+ cell noncytotoxic anti-HIV activity in individuals receiving highly active antiretroviral therapy during primary infection.

Recent advances in the ability to detect people at the early stages of HIV infection now permit the initiation of antiretroviral treatment before the full complement of antiviral immune responses has evolved. However, the influence of early treatment interventions on the developing anti-HIV immune response is unknown. This study investigates the impact of standard highly active antiretroviral therapy (HAART) during the primary stages of HIV infection on the plasma HIV-1 RNA level, CD4(+) and CD8(+) lymphocyte counts, and the CD8(+) cell anti-HIV response. Individuals treated with HAART within 6 months of infection showed dramatic and rapid reductions in HIV-1 RNA levels along with modest increases in CD4(+) cell number and decreases in CD8(+) cell numbers. A significant reduction in the level of CD8(+) cell noncytotoxic suppression of HIV replication was observed over time in most participants receiving HAART. Importantly, those individuals choosing not to receive therapy maintained low but detectable HIV-1 RNA levels and showed no reduction in their CD8(+) cell antiviral response. These results suggest that either continued antigenic challenge is required to sustain CD8(+) cell-mediated anti-HIV activity, or that HAART has some inhibitory effect on this important immunologic function during the early stages of infection.

Adult↗
PubMed2001

Longitudinal analysis of T-cell receptor gene use by CD8(+) T cells in early human immunodeficiency virus infection in patients receiving highly active antiretroviral therapy.

The effects of early antiretroviral therapy on the peripheral CD8(+) T-cell population were assessed by sequentially determining the T-cell receptor (TCR) repertoire complexity in a cohort of 15 individuals recently diagnosed with human immunodeficiency virus infection. Analysis was based on quantitative TCR variable B gene (TCRBV) usage and complementary-determining region 3 length assessment. Repertories were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. Early administration of highly active antiretroviral therapy has a positive effect on the preservation and homeostasis of the CD8(+) cell repertoire. Nevertheless, differences from average baseline and control TCR profiles and initial development of repertoire perturbations were observed. The findings suggest that additional therapeutic protocols will be required during primary infection to significantly prevent long-term erosion of the T-cell-mediated immune response.

Adult↗
PubMed2001

Evaluating HIV-infected patients with headache: who needs computed tomography?

OBJECTIVE: To empirically test a clinical prediction rule for evaluating HIV-infected patients complaining of headache and to identify those at low risk for intracranial mass lesion who do not need immediate computed tomography of the head. DESIGN: Two retrospective clinical cohorts of HIV-infected patients clinically evaluated for headache. METHODS: To describe the headache clinical outcomes, medical records were abstracted from all HIV-infected patients evaluated for headache with computed tomography of the head at two urban hospitals. Patients were categorized as low, intermediate, or high risk based on clinical criteria (focal neurological signs, altered mental status, history of seizure) and immune status (CD4 lymphocytes < or =200 microL). Records were abstracted from a second unselected cohort of HIV-infected outpatients with headache who were all treated and followed in primary care (N=101). RESULTS: Of 101 unselected HIV-infected outpatients followed in primary care after headache, 1% (95% confidence interval [CI], 0% to 6%) had a treatable intracranial lesion. Of 364 HIV-infected patients with headache sent for evaluation with computed tomography of the head, the rate of any abnormality was zero in the low-risk group (95% CI, 0% to 10%; n=35); 9% in the intermediate-risk group (95% CI, 2% to 16%; n=242); and 21% in the high-risk group (95% CI, 12% to 29%; n=87). CONCLUSION: Most HIV-infected patients with headache may be treated with analgesics and followed up clinically. Those without focal neurological signs, altered mental status, seizure, or decreased CD4 lymphocytes are unlikely to have intracranial mass lesions.

Adult↗
PubMed2001

Relative dominance of epitope-specific cytotoxic T-lymphocyte responses in human immunodeficiency virus type 1-infected persons with shared HLA alleles.

Cytotoxic T lymphocytes (CTL) target multiple epitopes in human immunodeficiency virus (HIV)-infected persons, and are thought to influence the viral set point. The extent to which HLA class I allele expression predicts the epitopes targeted has not been determined, nor have the relative contributions of responses restricted by different class I alleles within a given individual. In this study, we performed a detailed analysis of the CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A2, A3, and B7. The eight HIV-1-infected subjects studied included two subjects with acute HIV infection, five subjects with chronic HIV infection, and one long-term nonprogressor. Responses were heterogeneous with respect to breadth and magnitude of CTL responses in individuals of the same HLA type. Of the 27 tested epitopes that are presented by A2, A3, and B7, 25 were targeted by at least one person. However, there was wide variation in the number of epitopes targeted, ranging from 2 to 17. The A2-restricted CTL response, which has been most extensively studied in infected persons, was found to be narrowly directed in most individuals, and in no cases was it the dominant contributor to the total HIV-1-specific CTL response. These results indicate that HLA type alone does not predict CTL responses and that numerous potential epitopes may not be targeted by CTL in a given individual. These data also provide a rationale for boosting both the breadth and the magnitude of HIV-1-specific CTL responses by immunotherapy in persons with chronic HIV-1 infection.

Alleles↗
PubMed2000

Does HIV reporting by name deter testing? MESH Study Group.

OBJECTIVE: Name-based HIV reporting is controversial in the United States because of concerns that it may deter high-risk persons from being tested. We sought to determine whether persons at risk of HIV infection knew their state's HIV reporting policy and whether they had delayed or avoided testing because of it. DESIGN: A cross-sectional anonymous survey. METHODS: We interviewed 2404 participants in one of three high-risk groups: men who have sex with men (MSM), heterosexuals attending a sexually transmitted disease (STD) clinic, and street-recruited injection drug users (IDU). Participants were asked standardized questions about their knowledge of reporting policies and reasons for having delayed or avoided testing. We recruited in eight US states: four with name-based reporting and four without; all offered anonymous testing at certain sites. RESULTS: Fewer than 25% correctly identified their state's HIV reporting policy. Over 50% stated they did not know whether their state used name-based reporting. Of the total, 480 participants (20%) had never been tested. Of these, 17% from states with name-based reporting selected concern about reporting as a reason for not testing compared with 14% from states without name-based reporting (P = 0.5). Comparing previously tested participants from states with name-based reporting to those from states without, concern about HIV reporting was given as a reason for delaying testing by 26% compared with 13% of IDU (P < 0.001), and for 26% compared with 19% of MSM (P = 0.06). CONCLUSION: Most participants did not know their state's HIV reporting policy. Name-based reporting policies were not associated with avoiding HIV testing because of worry about reporting, although they may have contributed to delays in testing among some IDU.

AIDS Serodiagnosis↗
PubMed2000

Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population.

OBJECTIVE: To examine the relationship between adherence, viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor (PI) therapy. DESIGN AND SETTING: A cross-sectional analysis of subjects in an observational prospective cohort systematically sampled from free meal lines, homeless shelters and low-income, single-room occupancy (SRO) hotels. PARTICIPANTS: Thirty-four HIV-infected people with a median of 12 months of PI therapy. MAIN OUTCOMES: Adherence measured by periodic unannounced pill counts, electronic medication monitoring, and self-report; HIV RNA viral load; and HIV-1 genotypic changes associated with drug resistance. RESULTS: Median adherence was 89, 73, and 67% by self-report, pill count, and electronic medication monitor, respectively. Thirty-eight per cent of the population had over 90% adherence by pill count. Depending on the measure, adherence explained 36-65% of the variation in concurrent HIV RNA levels. The three adherence measures were closely related. Of 20 genotyped patients who received a new reverse transcriptase inhibitor (RTI) when starting a PI, three had primary protease gene substitutions. Of 12 genotyped patients who received a PI without a new RTI, six had primary protease gene substitutions (P < 0.03). CONCLUSION: A substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy. A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression. PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence.

Adult↗
PubMed2000

Quantitative and cost comparison of ultrasensitive human immunodeficiency virus type 1 RNA viral load assays: Bayer bDNA quantiplex versions 3.0 and 2.0 and Roche PCR Amplicor monitor version 1.5.

Quantification of human immunodeficiency virus type 1 (HIV-1) RNA as a measure of viral load has greatly improved the monitoring of therapies for infected individuals. With the significant reductions in viral load now observed in individuals treated with highly active anti-retroviral therapy (HAART), viral load assays have been adapted to achieve greater sensitivity. Two commercially available ultrasensitive assays, the Bayer Quantiplex HIV-1 bDNA version 3.0 (bDNA 3.0) assay and the Roche Amplicor HIV-1 Monitor Ultrasensitive version 1.5 (Amplicor 1.5) assay, are now being used to monitor HIV-1-infected individuals. Both of these ultrasensitive assays have a reported lower limit of 50 HIV-1 RNA copies/ml and were developed from corresponding older generation assays with lower limits of 400 to 500 copies/ml. However, the comparability of viral load data generated by these ultrasensitive assays and the relative costs of labor, disposables, and biohazardous wastes were not determined in most cases. In this study, we used matched clinical plasma samples to compare the quantification of the newer bDNA 3.0 assay with that of the older bDNA 2.0 assay and to compare the quantification and costs of the bDNA 3.0 assay and the Amplicor 1.5 assay. We found that quantification by the bDNA 3.0 assay was approximately twofold higher than that by the bDNA 2.0 assay and was highly correlated to that by the Amplicor 1.5 assay. Moreover, cost analysis based on labor, disposables, and biohazardous wastes showed significant savings with the bDNA 3.0 assay as compared to the costs of the Amplicor 1.5 assay.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Name-based surveillance and public health interventions for persons with HIV infection. Multistate Evaluation of Surveillance for HIV Study Group.

Name-based surveillance of HIV infection is the law in 31 U.S. states but remains controversial. This policy can be advocated solely to support surveillance of the epidemic, but a frequent argument is that it also provides a public health benefit by allowing follow-up of HIV-infected persons. These persons can then receive timely medical care and can be assisted with notifying sex and needle-sharing partners. Few comparative data are available to evaluate the outcomes of these interventions. In five states with name-based surveillance of HIV infection, the Multistate Evaluation of Surveillance for HIV Study Group surveyed a cross-sectional probability sample of persons with AIDS who tested positive for HIV before the date of their AIDS diagnosis. Health department follow-up of a reported HIV infection was not associated with more timely receipt of medical care after a positive HIV test result. Only 8.6% of persons who delayed medical care after their first positive HIV test result gave concern about being reported by name as a reason; no person gave it as the main reason. Persons who were tested anonymously and those who were tested confidentially did not differ in the mean number of sex and needle-sharing partners notified: Those tested anonymously reported personally notifying 3.85 sex and needle-sharing partners, and those tested confidentially reported notifying-personally and through the health department-3.80 partners. Many researchers and policymakers believe that name-based surveillance of HIV infection will have positive or negative effects on partner notification and access to health care. These results suggest that the potential for such effects has been exaggerated.

Anonymous Testing↗
PubMed1999

Optimizing care for persons with HIV infection. Society of General Internal Medicine AIDS Task Force.

Treatment advances and outcomes data have raised new concerns about how to optimize care for patients with HIV infection. This paper reviews evidence on 1) the relation between experience and type of training and patient outcomes, 2) the relation between the components of primary care and patient outcomes, and 3) primary care physicians' basic HIV knowledge and skills in screening and prevention. Several studies indicate that greater experience in HIV care leads to improved patient outcomes. The relation between outcomes and type of training (subspecialist or generalist) is less clear, and studies have not distinguished between type of training and experience. Less experienced physicians may be able to provide high-quality care if appropriate consultation from expert physicians is available. Components of primary care, including accessibility, continuity, coordination, and comprehensiveness, are associated with better patient outcomes. Optimal care of HIV infection requires a combination of disease-specific expertise and primary care skills and organization. Criteria for expertise in HIV management should focus on actual patient care experience and HIV expertise rather than on subspecialty training per se. The management of HIV has become sufficiently complex that primary care physicians cannot be routinely expected to have extensive specialized knowledge in this area. However, many primary care physicians have weaknesses in the basic HIV-related skills that are needed in most settings, such as HIV test counseling and recognition of important HIV-related symptom complexes. Primary care physicians need to strengthen these basic HIV-related medical skills.

Clinical Competence↗
PubMed1999

HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy.

OBJECTIVE: To determine the HIV RNA and CD4 cell response to both initial and salvage therapy with protease inhibitor-based therapy, and to examine the relationship between the virological response and pre-therapy characteristics. DESIGN: Observational cohort. SETTING: University-based public hospital AIDS clinic. PATIENTS: HIV-infected adults who received at least 16 continuous weeks' therapy with a potent protease inhibitor (indinavir, ritonavir or nelfinavir)-based regimen, and who have had at least 48 weeks of follow-up. MAIN OUTCOME MEASURES: Plasma HIV RNA and CD4 cell count response at week 48 of therapy for patients receiving their first protease inhibitor-containing regimen, and at week 24 of therapy with a salvage regimen. RESULTS: Of the 337 patients analysed, 170 (50.2%) had a successful outcome (HIV RNA <500 copies/ml after 48 weeks of treatment). Independent predictors of virological failure were higher baseline HIV RNA level, lower baseline CD4 cell count and failure to initiate at least one new nucleoside analog simultaneously at the time protease inhibitor therapy was initiated. The risk of failure increased incrementally across most HIV RNA and CD4 cell strata, with significant increases as the HIV RNA increased above 4.5 log10 copies/ml and the CD4 cell count fell below 100 cells/mm3 (P< or =0.01). The CD4 cell count remained above baseline to week 48 in most patients, regardless of the HIV RNA response. Of the 99 patients who experienced virological failure and switched to a salvage regimen, only 22 (22%) achieved an undetectable HIV RNA level 24 weeks after initiating salvage therapy. Independent predictors of failure with salvage therapy included an HIV RNA greater than 4.0 log10 RNA copies/ml at the time of the switch and failure to use a non-nucleoside reverse transcriptase inhibitor (NNRTI) in the salvage regimen. CONCLUSION: Failure of potent protease inhibitor therapy to suppress HIV RNA levels below detectable levels is common in clinical practice, and can often be explained by their suboptimal use. CD4 T cell counts remain above baseline for at least one year in most patients experiencing virological failure. Successful salvage therapy, which was uncommon, was associated with a low plasma HIV RNA at the time of the switch and the use of a new class of antiretroviral agents (NNRTI) in the salvage regimen.

Adult↗