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Biomedical subjects

H Weinstock

Publications and source records attributed to H Weinstock.

11 recordsLinked to original sources
PubMed2001

Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naive persons.

Transmission of HIV-1 with reduced susceptibility to antiretroviral drugs raises public health concerns. Through surveillance of drug-resistant HIV-1 in 603 treatment-naive, recently diagnosed HIV-1-infected persons, we identified a distinct group of viruses that have mutations at codon 215 of the reverse transcriptase (RT) gene that are different from either the wild-type (WT) T or the zidovudine (AZT)-selected T215Y/F. These mutations included 215D/C/S and were found in 20 patients (3.3%). The 215D, 215C, and 215S mutations differ from 215Y by a 1-nt change compared with 2 nt for the WT T215 and likely represent revertants of 215Y. These viruses all were found to have WT susceptibility to AZT, and all replicated efficiently as WT HIV-1(T215). However, differences in fitness among HIV-1(215D), HIV-1(215C), and HIV-1(215S) were seen when RT backgrounds were changed, demonstrating a role of the RT background in the selection of these revertants. In vitro selection with AZT showed that HIV-1(215D) and HIV-1(215C) acquired 215Y more rapidly than did WT HIV-1(T215), likely reflecting the need for only 1-nt change to evolve to 215Y. Our study demonstrates that HIV-1 with unusual mutations at codon 215 replicate efficiently, have WT susceptibility, and are commonly found in treatment-naive persons. The increased ability for selecting resistance mutations defines this class of WT HIV-1 and highlights the higher potential of these viruses to compromise the efficacy of antiretroviral therapy.

Anti-HIV Agents↗
PubMed2001

HIV incidence among repeat HIV testers at a county hospital, San Francisco, California, USA.

OBJECTIVES: To estimate HIV incidence, characterize correlates of HIV seroconversion, and monitor temporal trends in HIV transmission among patients repeatedly tested for HIV by a county hospital in San Francisco. DESIGN: Retrospective longitudinal study. METHODS: HIV incidence was retrospectively calculated among persons voluntarily tested for HIV antibody more than once at San Francisco's county hospital or one of its affiliated satellite community clinics between 1993 and 1999. Linkage of HIV test results in computerized databases identified "seroconverters" as individuals who had a negative antibody test followed by a positive test. The interval between tests was used as the person-time at risk. Cox proportional hazards analysis identified correlates of HIV seroconversion. RESULTS: A total of 84 HIV seroconversions were identified among 2893 eligible patients repeatedly tested for HIV antibody over a cumulative 5860 person-years (PYs) (incidence of 1.4 per 100 PYs, 95% confidence interval [CI]: 1.2-1.7). The majority of seroconversions (71 [84.5%]) were among injection drug users (IDUs) (incidence of 2.0 per 100 PYs, CI: 1.6-2.4). HIV incidence was highest among men who have sex with men (MSM) who were also IDUs (incidence of 3.8 per 100 PYs, CI: 2.7-5.1) and lowest among non-IDUs, heterosexual men, and non-IDU women (incidence of 0.3 per 100 PYs, CI: 0.1-0.6). In multivariate analysis, correlates of HIV seroconversion were age 25 to 29 years (hazard ratio [HR] = 3.9, CI: 2.4-6.3), MSM (HR = 2.9, CI: 1.9-4.4), and IDU (HR = 3.2, CI: 1.8-5.8). Overall, no temporal trend in annual HIV incidence was noted during the study period; however, HIV incidence among MSM IDUs increased from 2.9 per 100 PYs in 1996 to 4.7 per 100 PYs in 1998. CONCLUSIONS: The rate of seroconversion in this hospital and affiliated clinic population is unexpectedly high. Moreover, HIV transmission among IDU patients has not decreased over the last several years. The San Francisco county hospital provides a high-risk sentinel population to monitor emerging trends in HIV transmission, especially among IDUs, and presents multiple opportunities for prevention interventions, because these patients are being seen repeatedly by clinicians.

AIDS Serodiagnosis↗
PubMed2001

Analysis of dynamic cohort data.

Left-truncated and interval-censored data, termed dynamic cohort data, arise in longitudinal studies with rolling admissions and only occasional follow-up. The authors compared four approaches for analyzing such data: a constant hazard model; maximum likelihood estimation with flexible parametric models; the midpoint method, in which the midpoint of the last negative and first positive test result is used in a Cox proportional hazards model that accounts for left truncation; and a semiparametric method that uses imputed failure times in the Cox model. By using a simulation study, they assessed the performance of these approaches under conditions that can arise in observational studies: changes in disease incidence and changes in the underlying population. The simulation results indicated that the constant hazard model and midpoint method were inadequate and that the flexible parametric model was useful when enough parameters were used in modeling the baseline hazard. The semiparametric method ensured correct parameter (odds ratio) estimation when the baseline hazard was misspecified, but the trade-off increased computational complexity. In this paper, a study of the incidence of human immunodeficiency virus in patients repeatedly tested for the virus at a sexually transmitted disease clinic in New Orleans, Louisiana, illustrates the methods used.

Cohort Studies↗
PubMed2001

Differences in the temporal trends of HIV seroincidence and seroprevalence among sexually transmitted disease clinic patients, 1989-1998: application of the serologic testing algorithm for recent HIV seroconversion.

The authors compared temporal trends in the prevalence and incidence of human immunodeficiency virus (HIV) infection based upon 34,866 specimens from patients who attended the San Francisco, California, municipal sexually transmitted disease clinic between 1989 and 1998. HIV infection data were collected during annual blinded HIV serologic surveys. Incidence was determined by applying a serologic testing algorithm for recent HIV seroconversion that uses both a sensitive and a less sensitive enzyme immunoassay to stored HIV positive sera. The HIV seroprevalence declined from 15.2% in 1989 to 7.2% in 1998 (odds ratio per year = 0.92, 95% confidence interval (CI): 0.91, 0.94). Among homosexual men, the HIV prevalence declined from 50.9% in 1989 to 19.9% in 1998 (odds ratio per year = 0.86, 95% CI: 0.85, 0.88). The pooled seroincidence was 1.6% and did not change significantly over time (odds ratio per year = 1.0, 95% CI: 0.98, 1.1). The pooled seroincidence among homosexual men was 6.6% per year and remained steady between 1989 and 1998 (odds ratio per year = 0.99, 95% CI: 0.92, 1.1). During a dramatic, 10-year decline in seroprevalence of HIV infection, the incidence of HIV infection remained remarkably stable.

Adult↗
PubMed2001

Substitution model of sequence evolution for the human immunodeficiency virus type 1 subtype B gp120 gene over the C2-V5 region.

Phylogenetic analyses frequently rely on models of sequence evolution that detail nucleotide substitution rates, nucleotide frequencies, and site-to-site rate heterogeneity. These models can influence hypothesis testing and can affect the accuracy of phylogenetic inferences. Maximum likelihood methods of simultaneously constructing phylogenetic tree topologies and estimating model parameters are computationally intensive, and are not feasible for sample sizes of 25 or greater using personal computers. Techniques that initially construct a tree topology and then use this non-maximized topology to estimate ML substitution rates, however, can quickly arrive at a model of sequence evolution. The accuracy of this two-step estimation technique was tested using simulated data sets with known model parameters. The results showed that for a star-like topology, as is often seen in human immunodeficiency virus type 1 (HIV-1) subtype B sequences, a random starting topology could produce nucleotide substitution rates that were not statistically different than the true rates. Samples were isolated from 100 HIV-1 subtype B infected individuals from the United States and a 620 nt region of the env gene was sequenced for each sample. The sequence data were used to obtain a substitution model of sequence evolution specific for HIV-1 subtype B env by estimating nucleotide substitution rates and the site-to-site heterogeneity in 100 individuals from the United States. The method of estimating the model should provide users of large data sets with a way to quickly compute a model of sequence evolution, while the nucleotide substitution model we identified should prove useful in the phylogenetic analysis of HIV-1 subtype B env sequences.

Evolution, Molecular↗
PubMed2000

Prevalence of mutations associated with reduced antiretroviral drug susceptibility among human immunodeficiency virus type 1 seroconverters in the United States, 1993-1998.

To assess the prevalence of mutations associated with decreased antiretroviral drug susceptibility, specimens were tested from persons infected with human immunodeficiency virus (HIV) during 1993-1998. Subjects were drug naive and were attending sexually transmitted disease clinics in 6 US cities. All were enrolled consecutively and had tested negative for HIV during the 2 years before enrollment. Plasma specimens from patients having >/=1 reverse transcriptase (RT) or primary protease mutation were tested phenotypically with a recombinant virus assay. Of 99 patients, 6 (6%) had mutations associated with zidovudine resistance, 2 (2%) had mutations associated with nonnucleoside RT inhibitor resistance, and 1 (1%) had a primary protease mutation. Overall, the prevalence of resistance-associated primary mutations was 5%, although high levels of decreased drug susceptibility (IC(50)s >/=10 times that of a reference virus) were observed in just 1%. These findings confirm the transmission of these mutations to drug-naive persons.

Adolescent↗
PubMed1998

HIV seroincidence and risk factors among patients repeatedly tested for HIV attending sexually transmitted disease clinics in the United States, 1991 to 1996. STD Clinic HIV Seroincidence Study Group.

To assess the incidence of HIV infection and risk factors associated with HIV seroconversion among patients attending clinics for sexually transmitted diseases (STD), medical record reviews were conducted in 12 clinics in 7 U.S. cities. The records of all patients who initially tested negative for HIV from 1991 through 1996 and who received at least one additional HIV test during the study period were reviewed. In each of 7 cities, 5 to 112 patients seroconverted. Of the 286 seroconverters identified in total, 53% (152 of 286) were heterosexual men and 28% (81 of 286) were women. HIV incidence rates among men who have sex with men (MSM) ranged by city from 0.81 to 7.0 new infections/100 person-years. Rates among heterosexual men and women ranged from 0.018 to 1.2 infections/100 person-years. Multivariate analyses showed that drug use was associated with HIV seroconversion only among heterosexuals. Most new HIV infections in these clinics are being transmitted heterosexually and are associated with drug use. Nevertheless, MSM, particularly young MSM, are at greatest risk for HIV in this population: 1 of 47 seroconvert/year. The effective use of targeted prevention efforts depends upon the continued ability to monitor the incidence of HIV infection.

Adult↗
PubMed1994

Chlamydia trachomatis infections.

Chlamydia trachomatis infections are the most common bacterial cause of sexually transmitted disease in the United States. Although precise incidence of infection is not known, it has been calculated that more than 4 million chlamydial infections occur each year. This article discusses the epidemiology of sexually transmitted chlamydial infections, the spectrum of clinical manifestations and their sequelae, the laboratory diagnosis of genital infections, and antibiotic treatment, emphasizing the significance of these issues for control efforts in the United States.

Adolescent↗
PubMed1977

Bancroftian filariasis in Puerto Limón, Costa Rica.

In four neighborhoods of Puerto Limón, a Caribbean coastal city in a tropical rainforest area of Costa Rica, examination of 1-ml samples of night blood from 1,142 randomly selected, and 1,196 associated, persons by the Knott and filter-chamber techniques revealed microfilariae of Wuchereria bancrofti in about 3% of the 2,338 samples. The frequency of infection was higher in males (3.9%) than in females (1.9%), higher in persons of black (4.1%) than of white (1.0%) race, and highest in persons aged 10-19 (4.0%) and over 50 years (4.8%), lowest in those under 10 years (1.1%). The median microfilaria density was 3.5, the highest 45, per 20 lambdas of blood. Microfilaremia was distinctly periodic. Dissection of 663 female Culex pipiens fatigans from 42 houses of infected persons revealed filarial larvae in 25; only 1 larva was third (infective) stage. Of 64 infected persons, 11 had clinical findings suggestive of filariasis. Elephantiasis was seen in 21 others. Other forms of symptomatic filariasis without microfilaremia, though presumed to be present, were not assessed specifically.

Adolescent↗