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Biomedical subjects

D Katzenstein

Publications and source records attributed to D Katzenstein.

At least 37 records · Page 2Linked to original sources
PubMed1998

Sexual behaviour and risk assessment of HIV seroconvertors among urban male factory workers in Zimbabwe.

Despite extensive HIV prevention programmes and knowledge of people dying of AIDS, people in Zimbabwe continue to be infected with HIV and other sexually transmitted infections (STIs). This paper presents selected case histories from interviews with 57 men who became HIV positive during follow up of 1678 seronegative male factory workers in Harare, and describes the circumstances in which they were exposed to infection. Youth was a major risk factor, with 47% of those who seroconverted aged between 18 and 24 yr. STIs were reported by 23% of the group in the seroconversion period, a marker of unprotected sex. Individuals did not recognise themselves or their partners as candidates for infection because of categorisation of high risk groups as "promiscuous" or clients of sex workers. Many were optimistic that they had changed sufficiently by using condoms more often or by avoiding sex workers. They made inaccurate assessments of who was safe for unprotected sex, based on judgements about their character, background and age. Over 40% of the seroconvertors had previously been counselled on staying HIV negative. Community approaches which nurture development of supportive group norms, respect for human rights and responsibilities, and safe environments for disclosure of HIV status, are vital for overcoming denial of risk at individual and societal levels. Special efforts targeted at youth are crucial since they have the highest risk of new infections and include use of media, drama, role models, advisory centres, peer education programmes. Health professionals need training and skills to enable people at risk of HIV infection to devise strategies based on more realistic personal risk assessment.

Adolescent↗
PubMed1998

Risk factors for HIV seropositivity among first-time blood donors in Zimbabwe.

BACKGROUND: Factors associated with an increased likelihood of HIV infection among newly recruited blood donors in Zimbabwe are identified. Their feasibility as criteria for exclusion from donation is assessed. STUDY DESIGN AND METHODS: A self-administered survey including demographic and behavioral questions was completed by 1199 first-time, volunteer blood donors in Harare, Zimbabwe. Methods for subject recruitment and laboratory screening followed usual blood bank protocols. RESULTS: Fifteen percent of subjects were HIV positive. Factors significantly associated with HIV seropositivity at the p<0.05 level included recruitment venue, age, marital status, donor residence, residence of primary partner, occupation, history of sexually transmitted disease, and condom use. An exclusion strategy based on donor age, condom use, recruitment venue, sexually transmitted disease history, and residence of primary partner would exclude a large proportion of HIV-infected donors without substantial loss of uninfected donors. CONCLUSIONS: Exclusion of donors who are likely to be infected with HIV is a sound policy for improving blood safety and reducing operating costs worldwide. Identification of efficient donor selection criteria requires knowledge of the local epidemiology of HIV infection and the asking of questions that are likely to be answered accurately.

Adult↗
PubMed1998

Mortality in the first 2 years among infants born to human immunodeficiency virus-infected women in Harare, Zimbabwe.

Transmission of human immunodeficiency virus (HIV) and mortality was studied among infants of infected women in Zimbabwe. Of 367 infants born to HIV-infected women, 72 (19.6%) died compared with 20 (5.4%) of 372 infants of uninfected women (P < .01). Infection by HIV DNA polymerase chain reaction among infants who survived >7 days and died within 2 years could be assessed in 87% (58/67) of infants of infected women and 83% (5/6) of infants of uninfected women; transmission occurred in 40 of 58 infants. Among 27 infected infants tested at birth, 19 (70%), 5 (19%), and 3 (11%) were apparently infected via in utero, intrapartum or early postpartum, and late postpartum transmission, respectively. The majority of HIV-infected infants who died in the first 2 years of life were likely to have acquired in utero infection.

Adult↗
PubMed1998

Association between human immunodeficiency virus and herpes simplex virus type 2 seropositivity among male factory workers in Zimbabwe.

To determine the seroprevalence of herpes simplex virus type 2 (HSV-2), to identify correlates of infection, and to describe the correlation with human immunodeficiency virus (HIV) seropositivity, 224 HIV-negative and 191 HIV-positive male factory workers in Zimbabwe were screened for HSV-2-specific antibodies. HSV-2 seroprevalence was 35.7% among HIV-negative subjects and 82.7% among HIV-positive subjects. The weighted estimate of HSV-2 seroprevalence in this population is 44.6%. The correlation between HIV and HSV-2 remained significant after controlling for multiple sex partners, paying for sex, and history of sexually transmitted disease (adjusted odds ratio, 8.0; 95% confidence interval, 4.8-13.1). If the association between HSV-2 and HIV is causal, then the high seroprevalence of HIV and HSV-2 suggests that suppressive HSV-2 treatment should be considered as a strategy to reduce HIV transmission in this population. HSV-2 seroconversion may be a suitable surrogate end point to evaluate HIV prevention interventions.

Adolescent↗
PubMed1998

Human immunodeficiency virus type 1 RNA shedding in the female genital tract.

Cervical and plasma samples obtained twice, at 2-week intervals, from 49 human immunodeficiency virus type 1 (HIV-1)-positive women were assayed for HIV-1 RNA. More than 100 copies of HIV-1 RNA were detected in cervical swab supernatants (CSS) from 24 (49%) of 49 women. HIV-1 RNA in CSS was detected in younger women with higher levels of plasma HIV-1 RNA (median, 31,984 vs. 2880 copies/mL; P = .0004), lower CD4 cell counts (median, 190 vs. 390 per mm3; P = .012), and lower CD4 cell percents (median, 16% vs. 25%; P = .03). In multiple logistic regression analysis, only plasma HIV-1 RNA was significantly associated with CSS HIV-1 RNA, with an odds ratio of 4.79/log10 increase in plasma HIV-1 RNA (95% confidence interval, 1.4-16; P = .01). Detection of HIV-1 RNA in cervical secretions is primarily associated with increased plasma HIV-1 RNA.

Adult↗
PubMed1998

Human immunodeficiency virus type 1 populations in blood and semen.

Transmission of human immunodeficiency virus type 1 (HIV-1) usually results in outgrowth of viruses with macrophage-tropic phenotype and consensus non-syncytium-inducing (NSI) V3 loop sequences, despite the presence of virus with broader host range and the syncytium-inducing (SI) phenotype in the blood of many donors. We examined proviruses in contemporaneous peripheral blood mononuclear cells (PBMC) and non-spermatozoal semen mononuclear cells (NSMC) of five HIV-1-infected individuals to determine if this preferential outgrowth could be due to compartmentalization and thus preferential transmission of viruses of the NSI phenotype from the male genital tract. Phylogenetic reconstructions of approximately 700-bp sequences covering the second constant region through the fifth variable region (C2 to V5) of the viral envelope gene revealed distinct variant populations in the blood versus the semen in two patients with AIDS and in one asymptomatic individual (patient 613), whereas similar variant populations were found in both compartments in two other asymptomatic individuals. Variants with amino acids in the V3 loop that predict the SI phenotype were found in both AIDS patients and in patient 613; however, the distribution of these variants between the two compartments was not consistent. SI variants were found only in the PBMC of one AIDS patient but only in the NSMC of the other, while they were found in both compartments in patient 613. It is therefore unlikely that restriction of SI variants from the male genital tract accounts for the observed NSI transmission bias. Furthermore, no evidence for a semen-specific signature amino acid sequence was detected.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Impact of HIV counselling and testing on HIV seroconversion and reported STD incidence among male factory workers in Harare, Zimbabwe.

OBJECTIVES: To assess the impact of HIV counselling and testing on HIV seroconversion and incidence of reported sexually transmitted diseases (STDs) among male factory workers in Harare, Zimbabwe. DESIGN: Prospective, observational study among men recruited to participate in a future workplace based AIDS prevention intervention. METHODS: Participants provided STD histories and blood for HIV antibody testing at enrolment and six month intervals during visits to factories. Participants received HIV test results, post test counselling, and free STD services at the project clinic. RESULTS: Between March 1993 and June 1995, 2,414 men were enrolled with 85% follow up. Overall HIV sero-incidence was 2.60 per 100 person-years; the incidence of reported STDs was 10.19 per 100 person-years. Men who obtained their HIV test results had significantly higher HIV sero-incidence and incidence of reported STDs compared to men who did not obtain their results (IRRs: 1.87, 3.47, respectively). Among men who obtained their HIV test results, a non-significant 40% decrease in HIV sero-incidence was observed after obtaining test results compared to before obtaining results (p = 0.18). The incidence of reported STDs, however, increased by 30% after obtaining HIV test results (p = 0.10). CONCLUSIONS: Decreased HIV sero-incidence in the face of increased reported STD incidence suggests that timely treatment of STDs may decrease the risk of acquiring HIV even in the absence of behaviour change. In populations with high rates of HIV and STDs, the greatest benefit of HIV counselling and testing may be achieved by simultaneously offering STD screening and treatment services.

AIDS Serodiagnosis↗
PubMed1997

Effect of therapeutic immunization with recombinant gp160 HIV-1 vaccine on HIV-1 proviral DNA and plasma RNA: relationship to cellular immune responses.

Therapeutic vaccination has been proposed as a strategy to augment immune mechanisms to control viral replication and slow clinical progression of HIV infection to disease. Following recombinant gp160 (r-gp160) immunization in three clinical trials, plasma HIV-1 RNA and cellular proviral DNA were assessed by quantitative polymerase chain reaction (PCR) in 76 HIV-seropositive subjects with CD4+ T cell counts > or = 300/mm3. Immunization increased HIV-specific cellular immune responses (e.g., cytotoxic T lymphocyte [CTL] activities, lymphocyte proliferative responses); however, there were no significant effects of immunization or cellular immune responses on measures of plasma RNA or cellular DNA viral load.

AIDS Vaccines↗
PubMed1997

Measuring quality of life in early HIV disease: the modular approach.

RATIONALE: to examine the reliability and validity of the General Health Self-assessment, a modular questionnaire for self-assessment of quality of life (QoL) in human immunodeficiency virus (HIV) clinical trials and to describe the baseline QoL of participants in a large HIV clinical trial. DESIGN: the domains assessed include health perceptions, physical, psychological and role/social functioning, health care utilization and symptom distress. METHOD: 1,694 subjects with early HIV infection enrolled in the AIDS Clinical Trials Group Protocol 175 completed the scale at baseline. RESULTS: the domains demonstrated reliability, construct and discriminant validity. A worse QoL was associated with recent hospitalization and symptomatic status. Prior antiretroviral therapy was associated with higher health perceptions and well-being. The presence of symptom distress was related to lower QoL on the other scales. There was no relationship between QoL scales and the baseline CD4 count. Women showed a lower QoL than men on all scales, while ethnicity was related to differences in health perceptions and physical and psychological functioning. CONCLUSIONS: the General Health Self-assessment shows excellent potential as a measure of QoL for HIV-infected patients in clinical trials. Further research is necessary to determine the responsiveness of the scale to clinical and immunological changes in HIV-infected individuals.

Adolescent↗
PubMed1997

Risk factors for prevalent and incident HIV infection in a cohort of volunteer blood donors in Harare, Zimbabwe: implications for blood safety.

OBJECTIVES: To compare risk factors for HIV seropositivity with risk factors for HIV seroconversion in a population of volunteer blood donors in Harare, Zimbabwe, and to assess the impact of risk factor exclusion strategies on the safety of the blood supply. DESIGN: A secondary analysis of a longitudinal cohort study was performed. SUBJECTS AND METHODS: The subjects were volunteer blood donors who were also taking part in a prospective cohort study in Harare, Zimbabwe. They were tested for HIV antibodies upon enrollment and at 6-month intervals. Their donation history, age, marital status and the presence or absence of multiple sex partners and paying for sex were assessed as predictors of HIV seropositivity and HIV seroconversion. The impact of exclusion strategies on blood safety was modeled by estimating the number of HIV-infected units that would escape detection by antibody screening if blood donors with these risk factors were excluded. RESULTS: The HIV seroprevalence among persons accepted for blood donation was 8.8%; the HIV seroincidence was 2.1 per 100 person-years. Significant risk factors for HIV seropositivity were being a new donor (odds ratio 7.3, 95% confidence interval 4.4-1 2.1), age over 25 years (odds ratio 1.6, confidence interval 1.1-2.4), being married (odds ratio 1.7, confidence interval 1.2-2.6), paying for sex (odds ratio 2.6, confidence interval 1.7-3.9) and multiple sex partners (odds ratio 2.1, confidence interval 1.4-2.9). Significant risk factors for HIV seroconversion were age under 25 years (hazard ratio 2.5, confidence interval 1.4-5.0) and being unmarried (hazard ratio 2.5, confidence interval 1.4-5.0). Of note, age and marital status reversed their direction of association with respect to HIV seropositivity and HIV seroconversion. Exclusion strategies based on strong predictors of HIV seroconversion were the most effective in improving the safety of the blood supply. CONCLUSIONS: A distinction between risk factors for HIV seropositivity and HIV seroconversion is necessary in order to develop strategies to reduce the residual risk of transfusion-associated HIV transmission. Because window-period donations are the most important source of residual HIV contamination and arise from incident infections, research to develop risk factor exclusion strategies must focus on predictors of HIV seroconversion.

Adolescent↗
PubMed1997

HIV seroconversion among factory workers in Harare: who is getting newly infected?

OBJECTIVE: Zimbabwe, like other countries in sub-Saharan Africa, is experiencing a rapidly growing HIV/AIDS epidemic. It is crucial to determine risk events and socio-demographic characteristics associated with incident infections in order to tailor prevention messages accordingly. A cohort was established among factory workers with the objectives of estimating HIV incidence, seroprevalence, correlates of infection and subsequently evaluating the impact of prevention interventions. SETTING: 40 factories in Harare, Zimbabwe. DESIGN AND METHODS: HIV seroindicence [total new infections over person time (years) follow up] was estimated in a longitudinal cohort of male factory workers before and during a randomised peer education intervention. Correlates of seroconversion were identified using Cox regression analysis. RESULTS: Of 2,992 subjects enrolled there were 129 seroconversions during 1993 to 1996 follow up, yielding a 2.96 per 100 person year (PY) seroconversion incidence (95% CI = 2.47 to 3.52). Reporting a genital ulcer during follow up (Hazard ratio [HR] = 4.9, p = 0.001) having multiple sexual partners (HR = 1.9, p = 0.04), having a urethral discharge (HR = 2.1, p = 0.001), being single (HR = 2.3, p = 0.001), widowed or married but not residing with wife were independent factors significantly associated with risk of HIV seroconversion. CONCLUSIONS: Incidence of HIV identified in this economically productive sector is unacceptably high, and, disturbingly, is increasing in some age groups. Although the impact of the present intervention remains to be evaluated, the high incidence of HIV infection, points to the need for a more aggressive prevention effort in the general population.

Adult↗
PubMed1996

A randomized, placebo-controlled study of the immunogenicity of human immunodeficiency virus (HIV) rgp160 vaccine in HIV-infected subjects with > or = 400/mm3 CD4 T lymphocytes (AIDS Clinical Trials Group Protocol 137).

Immune responses provoked by human immunodeficiency virus (HIV) infection ultimately are insufficient to control the disease and do not include strong lymphocyte-proliferative responses to HIV antigens or antibodies to many viral epitopes. A randomized double-blind, placebo-controlled trial evaluated the immunogenicity of recombinant HIV envelope vaccine (rgp160) in HIV-infected subjects with > or = 400/mm3 CD4 T cells. Controls received hepatitis B vaccine. Of subjects receiving rgp160, 98% developed lymphocyte-proliferative responses to the immunogen, 33% to a different envelope protein, and 56% and 60% to p24 and p66, respectively. All doses of vaccine (20, 80, 320, 1280 microgram) induced new responses. New antibodies to epitopes on rgp160 developed only in recipients of higher doses of rgp160. CD4 T cell percentages declined less rapidly in recipients of rgp160 than in controls. Vaccination of HIV-infected subjects with rgp160 results in cellular and humoral immune responses to HIV that infection itself had not stimulated.

AIDS Vaccines↗
PubMed1996

Human immunodeficiency virus reverse transcriptase codon 215 mutations diminish virologic response to didanosine-zidovudine therapy in subjects with non-syncytium-inducing phenotype.

Eight zidovudine-experienced subjects received zidovudine and didanosine for 30 weeks followed by 30 weeks of didanosine monotherapy. At study entry, plasma from 4 subjects had human immunodeficiency virus RNA pol T215Y/F mutant and 4 had codon 215 wild type. All 8 subjects had non-syncytium-inducing virus phenotype. Sustained 10-fold decreases in plasma RNA levels were seen only in subjects who initially had 215 wild type RNA, despite the development of a T215Y/F mutation during combination therapy. Virologic and immunologic benefits were maintained in this group with didanosine monotherapy. No subject developed a pol L74V codon mutation. Significant differences in plasma virus load and CD4 cell responses were seen in this zidovudine-didanosine combination pilot study relative to codon 215 genotype.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Human immunodeficiency virus in plasma and genital secretions during the menstrual cycle.

Six human immunodeficiency virus (HIV)-positive women were studied weekly over 8 weeks to detect HIV RNA in plasma and cervical secretions and proviral DNA in cervical, vaginal, and cervicovaginal lavage samples by polymerase chain reaction (PCR) amplification techniques. In cervical swab samples, cell-free HIV RNA was detected more frequently than cell-associated HIV proviral DNA (22/48 vs. 7/48, respectively). Cervical HIV RNA was consistently detected in 2 women with plasma HIV RNA > 100,000 copies/mL but was not detected in 2 women with plasma HIV RNA < 10,000 copies/mL, regardless of menstruation status. HIV-specific IgA was detected in the plasma of 2 women and in at least 1 cervicovaginal lavage sample from all 6 women. Thus, quantitation of cervical HIV RNA can be accomplished by PCR techniques and may be useful in evaluation genital viral shedding.

Adult↗
PubMed1996

HIV seroincidence and correlates of seroconversion in a cohort of male factory workers in Harare, Zimbabwe.

OBJECTIVES: Given that health promotion messages on transmission of HIV and other sexually transmitted diseases (STD) have been widely publicized in Zimbabwe and elsewhere in the late 1980s, it is vital to analyse which risk events still expose individuals to infection. A cohort was established with the objectives of estimating HIV seroincidence, behavioural and biological determinants of infection, and ultimately, evaluating the impact of AIDS prevention interventions in the workplace. METHODS: HIV seroincidence was estimated in a prospectively followed cohort of male factory workers recruited in Harare, Zimbabwe during the period prior to a workplace AIDS prevention intervention. Correlates of HIV seroconversion were identified using Cox regression analysis. RESULTS: There were 51 seroconversions among 1607 HIV-negative participants following 1738 person-years (PY) of observation [seroincidence, 2.93 per 100 PY; 95% confidence interval (CI), 2.18-3.86]. The prevalence of HIV in the cohort was 19.1%. HIV seroincidence was significantly increased among men who were younger [hazard ratio (HR) per year, 0.96; 95% CI, 0.93-0.99], were single (HR, 3.29; 95% CI, 1.56-6.96), were married but resided separately from their wives (HR, 2.18; 95% CI, 0.99-4.80), reported having any STD (HR, 3.00; 95% CI, 1.53-5.86), reported having a genital ulcer (HR, 4.87; 95% CI, 2.18-10.91), and reported paying for sex (HR, 2.01; 95% CI, 1.06-3.77). Seroincidence also increased with the number of sex partners reported in the year preceding enrolment (HR per partner, 1.10; 95% CI, 1.01-1.21). In multiple Cox regression analysis, three independent associations with HIV seroconversion were reporting a genital ulcer (adjusted HR, 3.55; 95% CI, 1.52-8.29), number of sex partners (adjusted HR, 1.10; 95% CI, 1.01-1.21), and being married but residing separately from one's wife (adjusted HR, 2.21; 95% CI, 1.00-4.89). CONCLUSIONS: Innovative and sustained workplace-based interventions are needed to address the high risk of HIV infection in this economically productive population. The predictors of HIV seroconversion described in this study underscore the need for public health efforts to simultaneously address the biological, socioeconomic and behavioural factors that continue to place individuals at risk of HIV in general populations of Africa.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS Clinical Trials Group virology laboratories.

A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log10 RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons.

Clinical Protocols↗
PubMed1995

Safety, pharmacokinetics, and antiviral response of CD4-immunoglobulin G by intravenous bolus in AIDS and AIDS-related complex.

To assess the safety, pharmacokinetics, and antiviral effects of intravenous recombinant CD4 immunoglobulin G (CD4-IgG), a 12-week Phase One study with an optional maintenance phase was performed. Twenty-two subjects with advanced human immunodeficiency virus (HIV) infection were enrolled; 15 subjects completed the initial 12 weeks. CD4-IgG doses were 30, 100, or 300 micrograms/kg weekly; 1,000 micrograms/kg once, twice, or three times per week; or 3,000 micrograms/kg twice weekly. Serum concentrations of CD4-IgG increased linearly with dose, with average peak serum concentrations of 22 micrograms/ml with 1,000 micrograms/kg. CD4-IgG was well tolerated; one patient had self-limited tachycardia and flushing associated with CD4-IgG therapy. No changes were seen in CD4 cell counts, hematologic or coagulation studies, serum chemistries, HIV p24 antigen titers, or plasma HIV titers. No subject developed anti-CD4 antibodies. HIV isolates from five patients had IC90 values that were higher than the peak concentrations of CD4-IgG achieved in those patients. Additional studies that achieve higher CD4-IgG concentrations are necessary to evaluate the antiviral activity of this compound.

AIDS-Related Complex↗