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M L Kalish

Publications and source records attributed to M L Kalish.

At least 37 records · Page 2Linked to original sources

Sensitivity and specificity of a qualitative RNA detection assay to diagnose HIV infection in young infants. Perinatal AIDS Collaborative Transmission Study.

OBJECTIVE: To evaluate the sensitivity and specificity of an RNA detection assay for diagnosing perinatal HIV infection. METHODS: Plasma and serum specimens taken during the first 3 months of life from HIV-infected and uninfected children enrolled in a cohort study were assayed for HIV RNA using the qualitative nucleic acid sequence-based amplification (NASBA) kit. Sensitivity, specificity, and predictive values were calculated. NASBA results from infected children were compared with DNA PCR results from the same blood samples. Autoantibody patterns of suspected false-positive specimens were compared with those of subsequent specimens from the same child to exclude specimen labelling errors. RESULTS: Amongst 131 specimens from 105 HIV-infected children, the sensitivity of the qualitative NASBA assay was 13 out of 34 [38%; 95% confidence interval (CI), 22-56] at < 7 days, 56 out of 58 (97%; 95% CI, 88-100) at 7-41 days, and 37 out of 39 (95%; 95% CI, 83-99) at 42-93 days of life. Of 252 specimens from 206 uninfected children, six tested positive and one tested indeterminate by NASBA. Four of these positive specimens had discordant autoantibody patterns suggesting mislabelling; excluding these, the test specificity was 245 out of 248 (99%; 95% CI, 97-100). Amongst 128 paired specimens from infected children, NASBA results were more often positive than those from DNA PCR (103 versus 92; P=0.01). Amongst infants with specimens drawn in the first week of life, the proportion born after > 4 h of membrane rupture was greater amongst those testing negative (81%) than those testing positive (46%; P=0.05). CONCLUSIONS: The qualitative NASBA RNA assay is highly specific and more sensitive than DNA PCR. Qualitative RNA assays may be useful for diagnosing and excluding perinatal HIV infection in children after the first week of life for such purposes as initiating antiretroviral therapy and other treatment, resolving parental uncertainty, determining timing of transmission, and providing endpoints for intervention trials.

Cohort Studies↗

Genetic evaluation of suspected cases of transient HIV-1 infection of infants.

Detection of human immunodeficiency virus-type 1 (HIV-1) on only one or a few occasions in infants born to infected mothers has been interpreted to indicate that infection may be transient rather than persistent. Forty-two cases of suspected transient HIV-1 viremia among 1562 perinatally exposed seroreverting infants and one mother were reanalyzed. HIV-1 env sequences were not found in specimens from 20; in specimens from 6, somatic genetic analysis revealed that specimens were mistakenly attributed to an infant; and in specimens from 17, phylogenetic analysis failed to demonstrate the expected linkage between the infant's and the mother's virus. These findings argue that transient HIV-1 infection, if it exists, will only rarely be satisfactorily documented.

DNA, Viral↗

HIV type 1 in Thailand, 1994-1995: persistence of two subtypes with low genetic diversity.

Extensive transmission of human immunodeficiency virus type 1 (HIV-1) in Thailand began in 1988, resulting in an estimated 800,000 cumulative infections by 1994. During 1994 and 1995, we collected blood specimens from 215 asymptomatic HIV-1-infected people with various risk behaviors from nine locations in all four regions of Thailand. HIV-1 subtypes and genetic heterogeneity were determined for 214 strains by a combination of direct DNA sequencing (n = 95), subtype-specific oligonucleotide probe testing (n = 201), and V3-loop peptide enzyme immunoassay (PEIA) (n = 214). All strains were either env subtype E (175; 81.8%) or B (39; 18.2%). Of the subtype B isolates, 37 (94.9%) were B' and 2 (5.1%) were more typical North American-like B strains (most subtype B strains in Thailand are part of a distinct subcluster within the subtype B branch on phylogenetic trees, termed B'; formerly Thai B or BB). Of 149 viruses from people with sexual risk behaviors from all regions, 146 (98.0%) were subtype E. Of 65 viruses from injecting drug users (IDUs), 29 (44.6%) were subtype E and 36 (55.4%) were subtype B, including 35 B' strains. There was regional variation in the proportions of subtypes E and B' among IDUs. The intrasubtype nucleotide divergence within the V3 and flanking regions of the env gene (mid-C2 to the start of the V4 region) was low (5.7% for subtype E and 3.1% for subtype B') compared with other HIV-1 group M subtypes from different countries. These findings of two subtypes with low heterogeneity indicate that Thailand may be a desirable setting for evaluating candidate HIV-1 vaccines. The mix of subtype E and B' strains among IDUs also offers the opportunity to study phenotypic differences between the two subtypes.

Adolescent↗

Association of human immunodeficiency virus (HIV) load early in life with disease progression among HIV-infected infants. New York City Perinatal HIV Transmission Collaborative Study Group.

The utility of RNA virus load to predict progression of human immunodeficiency virus (HIV)-1 disease was assessed in 89 HIV-1-infected children. Of 22 virus load values during week 1 of life, 17 were below the detection threshold. Geometric mean virus load increased to approximately 7 x 10(5) copies/mL by week 4, was sustained throughout the first 6 months of life, and then declined to 1.6 x 10(5) copies/mL during the third year. Samples from week 1 of life had little predictive value, but virus load during days 7-30 strongly predicted progression to CDC-3 classification or death (P = .024; risk ratio = 1.6), and virus load during months 2-3 predicted progression to CDC-C or death within the first 6 months of life (P = .002, risk ratio = 11). Virus load was highly associated with imminent vulnerability to CDC-C or death (P = .002) during the first 18 months of life. Except for values from the first week of life, virus load at any age through 18 months is strongly associated with risk of HIV disease progression.

Child, Preschool↗

The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the effect of maternal viral load at delivery on the risk of perinatal transmission of HIV-1. DESIGN: A nested case-control study within a prospectively followed cohort of HIV-1-infected pregnant women and their infants. SETTING: The multicenter New York City Perinatal HIV Transmission Collaborative Study. PARTICIPANTS: Fifty-one women who gave birth to HIV-1 infected infants were frequency-matched within CD4+ cell count quintiles with 54 non-transmitting mothers. MAIN OUTCOME MEASURES: Maternal quantity of HIV-1 viral RNA was assayed in plasma obtained near delivery using the nucleic acid sequence-based amplification assay system. RESULTS: Viral RNA was detected in 73 (70%) out of 105 women and the median viral load was 16,000 RNA copies/ml in transmitters and 6,600 in non-transmitters (P < 0.01). When adjusted for maternal CD4+ count near delivery, women with measurable viral load were nearly sixfold more likely to transmit HIV-1 than women with viral load below detection [adjusted odds ratio (AOR), 5.8; 95% confidence interval (CI), 2.2 15.5]. The odds ratio for perinatal transmission of log10 viral load, adjusted for CD4 count was 2.7 (95% CI, 1.5-5.1). When stratified by the stage of HIV-1 disease, the only group with significant association between log10 viral load and transmission were AIDS-free women with CD4+ count > 500 x 10(6)/l (AOR, 9.1; 95% CI, 2.6-31.5). CONCLUSIONS: High maternal viral load increases the likelihood of perinatal transmission of HIV-1 in women without AIDS and advanced immunosuppression. HIV-1 infected pregnant women without advanced disease, shown by others to have the lowest risk of perinatal transmission, may benefit the most from efforts to identify and decrease viral load at delivery.

Adult↗

Effect of maternal CD4+ cell count, acquired immunodeficiency syndrome, and viral load on disease progression in infants with perinatally acquired human immunodeficiency virus type 1 infection. New York City Perinatal HIV Transmission Collaborative Study Group.

Among a cohort of 152 infants perinatally infected with human immunodeficiency virus type 1, and their mothers, we correlated infant outcome with material CD4+ lymphocyte count and the presence of maternal acquired immunodeficiency syndrome near delivery. In a subset of 50 mother-infant pairs, we also correlated infant outcome with maternal quantitative viral burden as measured by the nucleic acid sequence based amplification system. We found that low maternal CD4+ cell count and high viral burden were associated with decreased time to category C disease or death in infants infected with human immunodeficiency virus type 1. In a multivariate analysis, high maternal viral load and maternal acquired immunodeficiency syndrome were independently associated with shorter time to category C disease or death in infants with human immunodeficiency virus type 1 infection. High viral load in pregnant women, independent of the presence of advanced maternal disease, appears to increase the risk of rapidly progressive disease in their infected offspring.

Acquired Immunodeficiency Syndrome↗

Decision boundaries in one-dimensional categorization.

Decision-boundary theories of categorization are often difficult to distinguish from exemplar-based theories of categorization. The authors developed a version of the decision-boundary theory, called the single-cutoff model, that can be distinguished from the exemplar theory. The authors present 2 experiments that test this decision-boundary model. The results of both experiments point strongly to the absence of single cutoff in most participants, and no participant displayed use of the optimal boundary. The range of nonoptimal solutions shown by individual participants was accounted for by an exemplar-based adaptive-learning model. When combined with the results of previous research, this suggests that a comprehensive model of categorization must involve both rules and exemplars, and possibly other representations as well.

Decision Making↗

Diagnosis of perinatal human immunodeficiency virus infection by polymerase chain reaction and p24 antigen detection after immune complex dissociation in an urban community hospital.

Results of polymerase chain reaction (PCR) and p24 antigen detection after immune complex dissociation (p24-ICD) were compared with antibody results after 18 months of age for human immunodeficiency virus (HIV) diagnosis in 345 prospectively followed, perinatally exposed infants. Of 59 infected and 286 uninfected infants tested at 1-6 months of age, sensitivity and specificity were, respectively, 100% and > 97% for PCR and 90% and > 97% for p24-ICD. Testing was done on > or = 2 occasions in the first 6 months of life in 43 infected infants; 77% had > or = 2 positive results with the same test. Of these infants, 68% had 2 positive p24-ICD tests. In uninfected infants, 96% had only negative tests; none had > 1 positive. By 6 months, all uninfected infants with > or = 2 PCR results could have been diagnosed. HIV status can be determined by PCR by age 6 months in most HIV-exposed infants. p24-ICD should not be used alone, because of its lower sensitivity, but may be useful in areas without advanced laboratory support.

Antigen-Antibody Complex↗

Early detection of perinatal human immunodeficiency virus (HIV) type 1 infection using HIV RNA amplification and detection. New York City Perinatal HIV Transmission Collaborative Study.

Early diagnosis of perinatally transmitted human immunodeficiency virus type 1 (HIV) infection can guide early interventions. HIV coculture and DNA polymerase chain reaction (DNA-PCR) detect few HIV-infected infants at birth and 90%-100% by age 3 months. Because extracellular HIV RNA may appear soon after infection, a plasma HIV RNA assay was compared with DNA-PCR for early detection of perinatally infected infants. Blood-draw specimens (108) obtained at the same time from 49 HIV-infected infants and 10 specimens from 8 uninfected infants were tested. HIV RNA and DNA-PCR positivity rates were 56% and 33%, respectively, in 36 specimens from 36 infants <28 days of age (binomial test, P = .001). Among 81 specimens obtained after age 14 days, 79 (98%) were positive by HIV RNA testing. No HIV-infected infant specimens were DNA-PCR-positive and HIV RNA-negative. All specimens from 8 uninfected infants were HIV RNA-negative. These results suggest that plasma HIV RNA was detectable earlier and more reliably than HIV DNA in perinatal infection.

Female↗

The associations between cervicovaginal HIV shedding, sexually transmitted diseases and immunosuppression in female sex workers in Abidjan, Côte d'Ivoire.

OBJECTIVE: To measure the frequency and associated factors of cervicovaginal HIV shedding and to determine the impact of sexually transmitted disease (STD) treatment on HIV shedding. DESIGN: Cross-sectional study with 1-week follow-up. SETTING: Confidential clinic for female sex workers in Abidjan, Côte d'Ivoire. PARTICIPANTS: A total of 1201 female sex workers. INTERVENTIONS: STD treatment based on clinical signs. MAIN OUTCOME MEASURES: HIV serostatus; cervicovaginal HIV shedding at enrollment and at 1-week follow-up; STD status at enrollment and at 1-week follow-up. RESULTS: Cervicovaginal shedding of HIV-1 in HIV-1-seropositive women was more frequent (96 out of 404, 24%) than shedding of HIV-2 in HIV-2-seropositive women [one out of 21, 5%; odds ratio (OR), 6.2; 95% confidence interval (CI), 1.0-261]. Among 609 HIV-1-seropositive or dually seroreactive women, HIV-1 shedding was significantly more frequent in immunosuppressed women [adjusted OR (AOR), 6.3; 95% CI, 3.4-11.9; and AOR, 2.9; 95% CI, 1.6-5.0 for CD4 < 14% and CD4 14-28%, respectively, versus CD4 > 28%], and in women with Neisseria gonorrhoeae (AOR, 1.9; 95% CI, 1.2-3.0), those with Chlamydia trachomatis (AOR, 2.5; 95% CI, 1.1-5.8), and with a cervical or vaginal ulcer (AOR, 3.9; 95% CI, 2.1-7.4). HIV-1 shedding decreased from 42 to 21% (P < 0.005) in women whose STD were cured. CONCLUSIONS: These data help to explain the difference in transmissibility between HIV-1 and HIV-2 and the increased infectiousness of HIV in the presence of immunosuppression and STD. In addition, they lend biological plausibility to arguments for making STD control an integral part of HIV prevention strategies in Africa.

Adolescent↗

Titration of a vaccine stock preparation of human immunodeficiency virus type 1SF2 in cultured lymphocytes and in chimpanzees.

A large stock preparation of the HIV-1SF2 isolate has been derived after serial passage in human peripheral blood mononuclear cells (PBMCs). This viral stock has a titer of 10(4.9) TCID50 in human PBMCs and 10(4.2) TCID50 in chimpanzee PBMCs. By inoculation into animals the 50% chimpanzee infectious dose titer was found to be about 10(2.3). Virus isolation from animals was achieved on most occasions within 1-4 weeks after inoculation and then became transient. Viral RNA and DNA PCR analyses confirmed the virus infection of the chimpanzees. Anti-HIV antibody levels in the inoculated animals ranged from 1:400 to 1:6400 as measured by ELISA. About 680 vials of this stock preparation, frozen at -190 degrees C, are available for future studies of vaccines and antiviral therapies.

AIDS Vaccines↗

The emerging genetic diversity of HIV. The importance of global surveillance for diagnostics, research, and prevention.

The discovery of highly divergent strains of human immunodeficiency virus (HIV) not reliably detected by a number of commonly used diagnostic tests has underscored the need for effective surveillance to track HIV variants and to direct research and prevention activities. Pathogens such as HIV that mutate extensively present significant challenges to effective monitoring of pathogens and to disease control. To date, relatively few systematic large-scale attempts have been made to characterize and sequence HIV isolates. For most of the world, including the United States, information on the distribution of HIV strains among different population groups is limited. We describe herein the implications resulting from the rapid evolution of HIV and the need for systematic surveillance integrated with laboratory science and applied research. General surveillance guidelines are provided to assist in identifying population groups for screening, in applying descriptive epidemiology and systematic sampling, and in developing and evaluating efficient laboratory testing algorithms. Timely reporting and dissemination of data is also an important element of surveillance efforts. Ultimately, the success of global surveillance network depends on collaboration and on coordination of clinical, laboratory, and epidemiologic efforts.

AIDS Vaccines↗

Identification of single and dual infections with distinct subtypes of human immunodeficiency virus type 1 by using restriction fragment length polymorphism analysis.

The simultaneous presence of multiple HIV-1 subtypes has become common in communities with the growth of the pandemic. As a consequence, the potentiality for an increased frequency of HIV-1 mixed infections caused by viruses of distinct subtypes could be expected. Thus, there is a need to estimate the prevalence and geographic distribution of infections caused by viruses of a singular subtype as well as coinfections caused by two or more HIV-1 strains of distinct subtypes. To address this need, we have developed a genetic method based on restriction fragment length polymorphism (RFLP) to screen for these two types of infections within infected populations. In this assay, restriction enzymes may be used to predict the phylogroup of HIV-1 infected samples. A 297 bp pol fragment spanning the entire viral protease gene and a 311 bp fragment of the p24 gag region are used for this analysis. The viral regions are amplified by nested PCR using DNA templates from uncultured peripheral blood mononuclear cells (PBMC) or virus culture. Classification of HIV-1 strains to well defined subtypes B, D, F, and A/C is done by sequential endonuclease restriction analysis of a PCR amplified-protease gene followed by analysis of the p24 gag region. The electrophoretic migration patterns visualized by ethidium bromide staining or by radiolabeled probes are then determined on a 10% polyacrylamide gel. In infections caused by viruses of a singular subtype, a single restriction pattern is detected, whereas in multiple infections caused by two or more viral strains of different subtypes, the combination of different digestion patterns are observed in infected individuals. Using this methodology we have screened for genetic variations in HIV-1 proviral DNA from thirty-three Brazilian samples. Our RFLP procedure classified thirty-two samples as single infections caused by viruses of subtypes B (31) and F (1), and one sample as dual infection caused by distinct viral strains. Subsequent sequence and phylogenetic analysis of the viral protease gene in lymphocytes of all these patients confirmed our RFLP findings in single infections, and demonstrated the existence of two distinct HIV-1 strains of subtypes F and D in a patient which lymphocytes showed the simultaneous presence of two different digestion patterns. As up to now, single infections caused by subtype D variants were not identified in Brazil, our data provide the first evidence of subtype D HIV-1 in this country. Because sequencing of HIV proviral DNA is not particularly practical for large-scale molecular epidemiological studies, the protease/gag-based RFLP screening method will be useful to predict the phylogroup of HIV-1, and to identify multiple infections caused by HIV-1 strains of distinct subtypes. We believe that this information is crucial for both evaluation of the HIV-1/AIDS pandemic and intervention strategies.

Adult↗

Rapid molecular epidemiology of human immunodeficiency virus transmission.

Close sequence homology between strains of HIV-1 have been used to corroborate cases of epidemiologically identified transmission. As an alternative to extensive DNA sequence analysis, genetic relateness between pairs of HIV quasispecies was estimated using the reduced electrophoretic mobilities of HIV-1 envelope DNA heteroduplexes through polyacrylamide gels. All six infections acquired in a dental practice in the late 1980s and four of six infections acquired through blood product transfusions and sexual contact in 1984-1985 could be rapidly identified. A rising level of genetic diversity within HIV-1 subtype B facilitated the detection of later transmission events. Transmission linkages could be detected up to 4 years following infection. The simple and rapid technique of DNA heteroduplex tracking can therefore assist epidemiological investigations of HIV transmission and potentially of other genetically variable infectious agents.

Base Sequence↗