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Biomedical subjects

D A Katzenstein

Publications and source records attributed to D A Katzenstein.

At least 37 records · Page 2Linked to original sources
PubMed1999

Detection of Kaposi's sarcoma-associated herpesvirus in peripheral blood cells in human immunodeficiency virus infection: association with Kaposi's sarcoma, CD4 cell count, and HIV RNA levels.

Kaposi's sarcoma-associated herpesvirus (KSHV) DNA, consistently found in Kaposi's sarcoma (KS) tissues, was sought in peripheral blood mononuclear cells (PBMCs) of HIV-infected individuals. To determine quantitative relationships between the presence of KSHV DNA in PBMCs, CD4 cell counts, plasma HIV RNA levels, and the development of KS, we designed a cross-sectional study of prospectively collected PBMC samples from ongoing cohort studies. PBMCs were collected from 142 HIV-seropositive individuals in California, 7 of whom had a clinical diagnosis of KS. KSHV sequences were detected in extracted PBMC DNA by nested polymerase chain amplification using two nonoverlapping primer sets. KSHV DNA was detected in PBMCs of 5 of 7 (71%) subjects with KS and in 18 of 135 (13%) HIV-infected subjects without KS. Among HIV-seropositive individuals without KS, detection of KSHV was more common in men than women (19 versus 4%, p = 0.01) and was associated with lower mean CD4 percent (14.8 versus 20.7% CD4 cells, p = 0.03), lower mean CD4 cell count (244 versus 334 CD4 cells/microl, p = 0.05), and higher geometric mean plasma HIV RNA (4.83 versus 4.03 1og10 copies/ml, p = 0.0002). Semiquantitative analysis found 5 to 15,625 copies of KSHV per microgram of PBMC DNA with increased plasma HIV RNA levels and a trend toward increased subsequent development of KS in subjects with higher KSHV loads. The association of the presence of KSHV DNA in PBMCs with lower CD4 cell counts and higher plasma HIV RNA provides evidence of a relationship between immunosuppression, HIV replication, and KSHV expression.

Adult↗
PubMed1999

Serum level of maternal human immunodeficiency virus (HIV) RNA, infant mortality, and vertical transmission of HIV in Zimbabwe.

Maternal human immunodeficiency virus (HIV) RNA load, vertical transmission of subtype C HIV, and infant mortality were examined in 251 HIV-seropositive women and their infants in Zimbabwe. Demographic characteristics, health and medical histories, serum HIV RNA loads, and CD4+ lymphocyte counts for mothers were examined by logistic regression analysis to determine significant risk factors and their odds ratios for transmission and infant mortality. Tenfold (1 log10) incremental increases in maternal HIV RNA were associated with a 1.9-fold increase (95% confidence interval [CI], 1.2-2.9) in transmission and a 2.1-fold increase (95% CI, 1.3-3.5) in infant mortality (P<.01). Maternal CD4 cell counts and demographic and medical characteristics were not significant predictors of transmission. However, maternal CD4 cell counts below the median (400/mm3) were significantly associated with infant mortality (P=. 035, Fisher's exact test). The maternal level of serum HIV is an important determinant of vertical transmission and infant mortality in subtype C infection in Zimbabwe.

CD4 Lymphocyte Count↗
PubMed1999

Syphilis serology and HIV infection in Harare, Zimbabwe.

OBJECTIVE: To determine the reliability of serological tests in detecting syphilis in a factory worker cohort and examine the impact of concurrent HIV infection on serological tests for syphilis. METHOD: Reactions to non-treponemal and treponemal antigens were tested using sera from a cohort of 3401 factory workers in Harare, Zimbabwe. The participants consented to regular testing for syphilis, by VDRL, and HIV using two ELISAs. All sera from men who were VDRL positive, and a random sample of VDRL negative sera, were tested by RPR, TPHA, and where appropriate FTA-Abs. From the results, men were defined as having no syphilis, active syphilis, incident syphilis, historic syphilis, or giving biological false positive reactions. RESULTS: 709 sera were examined from 580 men. There were 78 cases of active syphilis in the cohort, giving a prevalence of 2.3%, and the seroincidence was 0.25 per 100 person years of follow up. The prevalence of HIV in the cohort was 19.8%. There was a strong association between syphilis, whether active, incident or historic, and HIV seropositivity. With both HIV positive and negative sera the negative predictive values of VDRL and RPR were > 99.9% while the positive predictive value for VDRL (30%) was lower than for RPR (39%). Biological false positive reactions were detected in 0.5% of the cohort, with in most cases a transient rise in VDRL titres up to < 1/16. Higher false positive titres occurred in five men, each of whom was HIV positive. CONCLUSIONS: The VDRL is reliable in detecting possible cases of syphilis even in a community with a high prevalence of heterosexually transmitted HIV. There is need, however, for confirmatory tests. The prevalence of syphilis in this cohort is very low in comparison with other countries in southern Africa, but is consistent with recent data from Harare. Despite a strong association between syphilis and HIV it was clear that syphilis could not be counted as a major factor fueling the HIV epidemic in Zimbabwe.

Cohort Studies↗
PubMed1998

Neuromuscular function in HIV infection: analysis of a placebo-controlled combination antiretroviral trial. AIDS Clinical Group 175/801 Study Team.

OBJECTIVE: To determine the frequency of peripheral neuropathy and myopathy in HIV-infected subjects enrolled in a combination antiretroviral treatment trial. DESIGN AND METHODS: AIDS Clinical Trial Group (ACTG) protocol 175 was a multicenter, double-blind, placebo-controlled, clinical trial. A total of 2467 subjects were randomized to one of four single or combination regimens, containing zidovudine (ZDV), didanosine (ddl), zalcitabine (ddC), and their respective placebos. Site investigators reported peripheral neuropathy, and the diagnosis of distal symmetrical neuropathy (DSP) was established by the study authors. Myalgia, muscle weakness and creatine phosphokinase (CPK) were prospectively assessed in a subset of the antiretroviral-naive cohort (n = 1067). RESULTS: Of 222 site diagnoses of neuropathy, 109 (49%) were DSP. There was a significant difference between treatment arms for rate of DSP and time to first grade 2 or higher DSP (ZDV-ddC, 6%; ZDV, 4%; ZDV-ddl, 4%; ddl, 3%; P = 0.029). Age and Karnofsky score were significant predictors of DSP. Fifty-six (54%) out of 104 patients with DSP remained on study medication at full (n = 29) or reduced (n = 27) dose within 6 months of developing neuropathy. There was no significant difference between treatment arms in the rate of myalgia or muscle weakness. The median CPK of subjects on ZDV-ddC was significantly higher than other study treatments, although CPK levels did not correlate with symptoms of myopathy. Only six subjects were diagnosed with myopathy during the study (one ZDV-ddl, one ZDV-ddC, and four ddl). CONCLUSIONS: DSP and myopathy may occur with current dosing regimens of combination antiretroviral therapy, and should be diagnosed using stringent criteria. ZDV-ddC was associated with the highest rate of DSP, although features of myopathy were not significantly different between treatment regimens.

Adult↗
PubMed1998

A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type 1 confers resistance to multiple nucleoside inhibitors.

While many point mutations in the HIV-1 reverse transcriptase (RT) confer resistance to antiretroviral drugs, inserts or deletions in this gene have not been previously characterized. In this report, 14 RT inhibitor-treated patients were found to have HIV-1 strains possessing a 6-basepair insert between codons 69 and 70 of the RT gene. Known drug resistance mutations were also observed in these strains, with T215Y appearing in all strains. Genotypic analysis indicated that the inserts had substantial nucleotide variability that resulted in relatively restricted sets of amino acid sequences. Linkage of patients' treatment histories with longitudinal sequencing data showed that insert strains appeared during drug regimens containing ddI or ddC, with prior or concurrent AZT treatment. Drug susceptibility tests of recombinant patient isolates showed reduced susceptibility to nearly all nucleoside RT inhibitors. Site- directed mutagenesis studies confirmed the role of the inserts alone in conferring reduced susceptibility to most RT inhibitors. The addition of AZT-associated drug resistance mutations further increased the range and magnitude of resistance. These results establish that inserts, like point mutations, are selected in vivo during antiretroviral therapy and provide resistance to multiple nucleoside analogs.

Amino Acid Sequence↗
PubMed1998

Estimating HIV incidence from age-specific prevalence data: comparison with concurrent cohort estimates in a study of male factory workers, Harare, Zimbabwe.

OBJECTIVE: To compare HIV incidence estimates from cross-sectional age-specific prevalence data with concurrent cohort estimates and to examine the sensitivity of the estimates to changes in age-categorization and survivorship assumptions. METHODS: Two previously described methods of estimating HIV incidence from cross-sectional prevalence data - the cumulative incidence and survival (CIS) and constant prevalence (CP) methods - are applied using data from a study of male factory workers in Harare, Zimbabwe. The methods are applied under two alternative groupings of the HIV prevalence data and under alternative survivorship assumptions: (a) Weibull distribution providing the best fit to the HIV prevalence data using the CIS method; (b) Weibull distribution matching data from an HIV natural history cohort study in Uganda; and (c) survivorship pattern as in (b) with survival periods reducing with increasing age at infection. Age-specific, age-standardized and cumulative HIV incidence estimates are calculated. The results are compared with concurrent longitudinal estimates from 3 years of follow-up of the Harare cohort (1993-1995). RESULTS: Age-standardized HIV incidence was estimated at 2.02 per 100 man years (95% CI, 1.57-2.47) in the cohort study. There was evidence of recent variability in HIV incidence in these data. Estimates from the cross-sectional methods ranged from 1.98 to 2.74 per 100 man years and were sensitive to changes in age-categorization of the HIV prevalence data and changes in survivorship assumptions. The cross-sectional estimates were higher at central ages and lower at older ages than the cohort estimates. The age-specific estimates from the CIS method were less sensitive to changes in age grouping than those from the CP method. CONCLUSIONS: HIV incidence remains high in Harare. Incidence estimates broadly consistent with cohort estimates can be obtained from single-round cross-sectional HIV prevalence data in established epidemics - even when the underlying assumption of stable endemic prevalence is not fully met. Estimates based on cross-sectional surveys should therefore be explored when reliable longitudinal estimates cannot be obtained. More data on post-HIV infection survivorship distributions in sub-Saharan Africa would facilitate the improvement of estimates of incidence based on cross-sectional surveys.

Adolescent↗
PubMed1998

Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society-USA Panel.

OBJECTIVE: To provide recommendations for antiretroviral therapy based on information available in mid-1998. PARTICIPANTS: An international panel of physicians with expertise in antiretroviral research and care of patients with human immunodeficiency virus (HIV) infection, first convened by the International AIDS Society-USA in December 1995. EVIDENCE: The panel reviewed available clinical and basic science study results (including phase 3 controlled trials; clinical, virologic, and immunologic end point data; data presented at research conferences; and studies of HIV pathophysiology); opinions of panel members were also considered. Recommendations were limited to drugs available in mid-1998. CONSENSUS PROCESS: Panel members monitor new clinical research reports and interim results. The full panel meets regularly to discuss how the new information may change treatment recommendations. Updated recommendations are developed through consensus of the entire panel at each stage of development. CONCLUSIONS: Accumulating data from clinical and pathogenesis studies continue to support early institution of potent antiretroviral therapy in patients with HIV infection. A variety of combination regimens show potency, expanding choices for initial regimens for individual patients. Plasma HIV RNA assays with increased sensitivity are important in monitoring therapeutic response; however, more data are needed to determine precisely the HIV RNA levels that define treatment failure. Long-term adverse drug effects are beginning to emerge, requiring ongoing attention. Some issues regarding optimal long-term approaches to antiretroviral management are unresolved. The increased complexity in HIV management requires ongoing monitoring of new data for optimal treatment of HIV infection.

Anti-HIV Agents↗
PubMed1998

HIV-1 reverse transcriptase codon 215 mutation in plasma RNA: immunologic and virologic responses to zidovudine. The AIDS Clinical Trials Group Study 175 Virology Team.

Treatment of HIV infection with zidovudine (ZDV) may select for changes in the genetic sequence of the viral reverse transcriptase (RT) that imparts drug resistance. The presence of a 2-bp mutation at codon 215 of RT (from threonine to phenylalanine or tyrosine) was assessed in plasma viral RNA in 85 subjects treated with ZDV in the AIDS Clinical Trials Group (ACTG) 175 virology substudy. Median CD4 cell numbers, HIV plasma RNA levels, and infectious titers of virus were significantly different over 56 weeks of treatment among 58 subjects with the wild-type threonine at codon 215 virus at study entry compared with the 27 subjects with mutations to phenylalanine or tyrosine (MUT) virus. Thirty percent (13 of 44 subjects) with wild-type virus at study entry developed a new codon 215 mutation. Genotypic resistance at codon 215 in plasma HIV RNA is associated with the subsequent immunologic and virologic failure of ZDV monotherapy in subjects with 200 to 500 CD4 cells/mm3.

Anti-HIV Agents↗
PubMed1998

Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy.

Data from 1330 human immunodeficiency virus type 1 (HIV-1)-infected patients enrolled in seven antiretroviral treatment trials were analyzed to characterize the clinical benefit of treatment-mediated reductions in plasma HIV-1 RNA levels. The risk of a new AIDS-defining event or death was reduced proportionally to the magnitude of the reduction of the HIV-1 RNA level during the first 6 months of therapy. Pretherapy HIV-1 RNA levels were prognostic independently of on-therapy levels. In addition, the reduction in risk associated with any given reduction of the level of HIV-1 RNA did not vary by pretherapy level. Having either a reduction in HIV-1 RNA level or an increase in CD4+ lymphocyte count, or both, was associated with a delay in clinical disease progression. This indicates that patient prognosis should be assessed using both HIV-1 RNA and CD4+ lymphocyte responses to therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Changes in virologic markers as predictors of CD4 cell decline and progression of disease in human immunodeficiency virus type 1-infected adults treated with nucleosides. AIDS Clinical Trials Group Protocol 175 Team.

The associations of CD4 cell count, plasma human immunodeficiency virus (HIV) type 1 RNA, infectious HIV titer in peripheral blood mononuclear cells, immune complex-disrupted (ICD) p24 antigen, and MT-2 assays with measures of disease progression after drug treatment were assessed in a subset of patients enrolled in AIDS Clinical Trials Group Study 175. Baseline plasma RNA levels and changes in RNA values at weeks 8 or 56 were more important predictors of disease progression than were baseline or changes in CD4 cell counts. Each 10-fold lower HIV RNA concentration at baseline and each 10-fold decrease in HIV RNA between baseline and week 8 was associated with increases of 49-61 CD4 cells/mm3 at weeks 56 and 104. In multivariate analyses, neither baseline values nor changes in infectious HIV titer nor ICD p24 antigen concentrations were associated with long-term changes in CD4 cell count. Plasma HIV-1 RNA appears to be the best predictor of long-term CD4 cell count responses and disease progression.

Adult↗
PubMed1998

Variability and prognostic values of virologic and CD4 cell measures in human immunodeficiency virus type 1-infected patients with 200-500 CD4 cells/mm(3) (ACTG 175). AIDS Clinical Trials Group Protocol 175 Team.

Virologic measurements are increasingly used to evaluate prognosis and treatment responses in human immunodeficiency virus (HIV) type 1 infection. Markers of HIV-1 replication, including infectious HIV-1 titer from peripheral blood mononuclear cells, serum HIV-1 p24 antigen, plasma HIV-1 RNA, CD4 cell numbers, and viral syncytium-inducing (SI) phenotype, were determined in 391 virology substudy participants in AIDS Clinical Trials Group study 175. The subjects had 200-500 CD4 cells/mm3. All markers of viral replication significantly correlated with one another and were inversely related to CD4 cell number. Disease progression to an AIDS-defining event or death or loss of >50% of CD4 cells was associated with infectious HIV-1 titer (P < .001), HIV-1 RNA (P < .001), and HIV-1 p24 antigen (P = .007). In multivariate proportional hazards models, p24 antigen was never significant when HIV-1 RNA level was included. In a model containing infectious HIV-1 titer (P = .038), HIV-1 RNA (P < .001), SI phenotype (P < .001), and CD4 cell number (P = .18), only the virologic parameters remained significantly associated with progression.

CD4 Lymphocyte Count↗
PubMed1998

Polymerase chain reaction detection of Haemophilus ducreyi DNA.

OBJECTIVES: To develop a polymerase chain reaction (PCR) method to detect Haemophilus ducreyi DNA in cultured isolates and clinical material. METHODS: Primers specific to the H ducreyi 16s rRNA gene were synthesised. PCR conditions were optimised and products were verified by restriction endonuclease digestion and agarose gel electrophoresis. RESULTS: The method was able to detect all 28 H ducreyi strains tested; specificity was demonstrated using lysates of 12 related organisms. Applied to clinical samples from genital ulcer swabs obtained in Harare, Zimbabwe, H ducreyi DNA was detected in repeated assays in 35 clinical samples. CONCLUSION: PCR amplification using primers from the 16s rRNA gene may be a useful alternative to culture for the detection of H ducreyi and the diagnosis of chancroid.

Chancroid↗
PubMed1997

Antiretroviral therapy for HIV infection in 1997. Updated recommendations of the International AIDS Society-USA panel.

OBJECTIVE: To provide current recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease. PARTICIPANTS: The original International AIDS Society-USA 13-member panel representing international expertise in antiretroviral research and care of patients with HIV infection. EVIDENCE: The following were considered: Newly available clinical and basic science study results, including phase 3 controlled trials; clinical, virological, and immunologic end-point data; interim analyses of studies presented at national and international research conferences; studies of HIV pathophysiology; and expert opinions of panel members. Recommendations were limited to the drugs available in mid 1997. PROCESS: The full panel met on a regular basis (July 1996, September 1996, November 1996, January 1997, and April 1997) since the publication of its initial recommendations in mid 1996 to review new research reports and interim results. The panel discussed whether and how new information changed its initial recommendations. The recommendations contained herein were determined by group consensus. CONCLUSIONS: New data have provided a stronger rationale for earlier initiation of more aggressive therapy than previously recommended and reinforce the importance of careful selection of initial drug regimen for each patient for optimal long-term clinical benefit and adherence. The plasma viral load is a crucial element of clinical management for assessing prognosis and the effectiveness of therapy, and such testing must be done properly. Treatment failure is most readily indicated by a rising plasma HIV RNA level and should be confirmed prior to a change of treatment. Therapeutic approaches must be updated as new data, particularly on the long-term clinical effect of aggressive antiretroviral treatment, continue to emerge.

Anti-HIV Agents↗
PubMed1997

Antimicrobial resistance in gonococci isolated from patients and from commercial sex workers in Harare, Zimbabwe.

The objective is to compare antibiotic resistance amongst gonococci isolated from different patient groups in Harare, Zimbabwe. Antimicrobial susceptibilities of Neisseria. gonorrhoeae were determined by disc sensitivity tests. The MICs for penicillin, kanamycin, ceftriaxone, norfloxacin and ciprofloxacin were determined using E-test strips. There were 147 isolates from symptomatic men, 47 isolates from symptomatic women, 29 isolates from asymptomatic women and 41 isolates from female commercial sex workers. A total of 119 (45%) isolates were PPNG and 23 (16%) non-PPNG isolates had a penicillin MIC > 0.64 mg/l. Over 90% of isolates were resistant to TMP/SMX and 16% were resistant to tetracycline. Resistance was uncommon against kanamycin (6%), erythromycin (2%) or ceftriaxone ( < 1%). For kanamycin, the MIC90 was 32 mg/l, for ceftriaxone the MIC90 was < 0.032 mg/l for non-PPNG and < 0.064 mg/l for PPNG. For norfloxacin and ciprofloxacin the MIC90 was < 0.064 mg/l for both PPNG and non-PPNG. Isolates from the commercial sex workers showed a significantly increased prevalence of PPNG, of penicillin-tolerant non-PPNG and of tetracycline resistance. Four of the 41 isolates from sex workers showed multiple resistance (to penicillin, TMP/SMX, tetracycline and kanamycin) compared to 1/223 isolates from other groups (OR = 24.0). Antimicrobial resistance is common amongst gonococci in Harare, especially with isolates from commercial sex workers. In order for STD treatment to be implemented as an effective strategy in HIV control, continued monitoring of resistance patterns is essential.

Anti-Bacterial Agents↗
PubMed1997

Adherence as a particular issue with protease inhibitors.

Suboptimal therapeutic doses of HIV protease inhibitors lead to the emergence of drug resistance and reduced drug efficacy. It is imperative, then, that patients and clinicians alike are fully educated about the importance of patients taking all the pills in these new, admittedly complex, antiretroviral regimens. With protease inhibitors especially, missing doses and/or taking drug holidays or partial doses will mean the rapid emergence of HIV isolates that are resistant to these drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1997

An evaluation of dipstick-dot immunoassay in the detection of antibodies to HIV-1 and 2 in Zimbabwe.

There is a need, in many developing countries, for simple and inexpensive HIV serology tests for use at the district level of health care. The Programme for Appropriate Technology in Health has developed a simple dipstick ELISA to detect antibodies to HIV-1 and 2, at a cost considerably lower than current ELISAs, which requires no specialized washing or reading equipment. In order to evaluate this dipstick under local conditions we used a panel of 546 sera selected from frozen stocks maintained by the Zimbabwe AIDS Prevention Project in Harare, Zimbabwe. Prior to storage, the sera had been tested by Abbott recombinant peptide HIV-1 and 2 ELISA and Enzygnost synthetic peptide HIV-1 and 2 ELISA. The panel included sera that were positive by both (including symptomatics and asymptomatics), negative by both, and sera showing discrepant test results. The panel was not representative of a "normal' batch of sera in Zimbabwe, and in particular included an abnormally high number of sera showing discrepant results. Thawed sera were retested using the Abbott recombinant peptide HIV-1 and 2 ELISA and concurrently with the synthetic peptide ICL-Dipstick ELISA. Both the sensitivity and specificity of the ICL Dipstick exceeded 99% when using sera that were positive or negative in all 3 plate ELISAs as the gold standard. When using sera that gave discrepant results between the two pre-storage ELISAs, most results with the ICL Dipstick concurred with findings from other test systems, including Western blot and p24 antigen detection. Considering the accuracy, low cost and case of operation of the ICL Dipstick ELISA, this test can be recommended for use for the rapid detection of antibodies to HIV at district level in developing countries.

Enzyme-Linked Immunosorbent Assay↗