Biomedical subjects

Hillard Weinstock

Publications and source records attributed to Hillard Weinstock.

10 recordsLinked to original sources

PubMed2007

Characteristics of persons with recently acquired HIV infection: application of the serologic testing algorithm for recent HIV seroconversion in 10 US cities.

BACKGROUND: Information about the characteristics of persons whose HIV diagnosis was made soon after infection contributes to a better understanding of the HIV epidemic and to appropriate targeting of care and prevention efforts. METHODS: In 10 US cities from 1997 through 2001, specimens from consenting persons for whom a diagnosis of HIV was made within the past 12 months in were tested using the serologic testing algorithm for recent HIV seroconversion. The characteristics of those whose HIV diagnosis occurred within 170 days (on average) from seroconversion were identified. RESULTS: For 191 (20%) of the 964 participants, an HIV diagnosis was made during the period of recent infection. These diagnoses of recent infection were made more frequently among men (21.7%), whites (29.3%), men who have sex with men (25.5%), persons with a known HIV-infected partner (24.9%), and persons with a diagnosis of gonorrhea made in the 12 months before interview (27.0%). Recent infection was diagnosed less frequently among African Americans (15.5%), Latinos (15.5), and heterosexual men (14.7%) and women (14.4%). CONCLUSIONS: To increase early diagnosis of HIV, HIV testing should be more routinely offered to persons with a recent history of sexually transmitted diseases and to African Americans and Latinos in a variety of settings.

AIDS Serodiagnosis↗

PubMed2004

Early syphilis in the United States identified in corrections facilities, 1999-2002.

BACKGROUND: Corrections facilities offer public health practitioners an opportunity to gain access to large numbers of persons at risk for syphilis and other sexually transmitted diseases. GOALS: The goals of this study were to estimate the number of early syphilis cases (primary, secondary, early latent) identified from corrections facilities from 1999 to 2002 and to determine characteristics of persons likely to be identified with syphilis in corrections facilities. STUDY DESIGN: We determined the proportion of cases identified from corrections facilities for the entire United States using case reports by state health departments to the Centers for Disease Control and Prevention (CDC). We calculated the proportion of cases identified in corrections facilities in the 30 counties with the largest number of cases in 2002 and determined the male-to-female syphilis rate ratios. RESULTS: From 1999 to 2002, there were 63,293 cases of early syphilis reported to the CDC, of which 61,691 (97.5%) had a known source of report. Of these, 7725 (12.5%) noted corrections facilities as the source of information. Among men, 4747 (13.0%) cases were from corrections and in women 2974 (11.8%) of cases were. We found that counties with a higher proportion of cases from corrections facilities were likely to have lower male-to-female rate ratios (r = -0.66, P <0.001). CONCLUSIONS: A substantial proportion of early syphilis cases is identified from corrections facilities. Among counties with the largest number of cases, a higher proportion of syphilis cases was identified from corrections facilities in counties with higher rates of heterosexually transmitted syphilis.

Adolescent↗

PubMed2004

Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine.

Drug-naive patients infected with drug-resistant human immunodeficiency virus type 1 (HIV-1) who initiate antiretroviral therapy show a shorter time to virologic failure than patients infected with wild-type (WT) viruses. Resistance-related HIV genotypes not commonly seen in treated patients, which likely result from reversion or loss of primary resistance mutations, have also been recognized in drug-naive persons. Little work has been done to characterize the patterns of mutations in these viruses and the frequency of occurrence, their association with phenotypic resistance, and their effect on fitness and evolution of resistance. Through the analysis of resistance mutations in 1082 newly diagnosed antiretroviral-naive persons from the United States, we found that 35 of 48 (72.9%) persons infected with HIV-1 containing thymidine analog mutations (TAMs) had viruses that lacked a primary mutation (T215Y/F, K70R, or Q151M). Of these viruses, 9 (25.7%) had only secondary TAMs (D67N, K219Q, M41L, or F77L), and all were found to be sensitive to zidovudine (AZT) and other drugs. To assess the impact of secondary TAMs on the evolution of AZT resistance, we generated recombinant viruses from cloned plasma-derived reverse transcriptase sequences. Two viruses had D67N, three had D67N and K219Q/E, and three were WT. Four site-directed mutants with D67N, K219Q, K219E, and D67N/K219Q were also made in HIV-1(HXB2). In vitro selection of AZT resistance showed that viruses with D67N and/or K219Q/E acquired AZT resistance mutations more rapidly than WT viruses (36 days compared to 54 days; P = 0.003). To investigate the factors associated with the rapid selection of AZT mutations in these viruses, we evaluated fitness differences among HXB2(WT) and HXB2(D67N) or HXB2(D67N/K219Q) in the presence of AZT. Both HXB2(D67N/K219Q) and HXB2(D67N) were more fit than HXB2(WT) in the presence of either low or high AZT concentrations, likely reflecting low-level resistance to AZT that is not detectable by phenotypic testing. In the absence of AZT, the fitness cost conferred by D67N or K219Q was modest. Our results demonstrate that viruses with unique patterns of TAMs, including D67N and/or K219Q/E, are commonly found among newly diagnosed persons and illustrate the expanding diversity of revertant viruses in this population. The modest fitness cost conferred by D67N and K219Q supports persistence of these mutants in the untreated population and highlights the potential for secondary transmission. The faster evolution of these mutants toward AZT resistance is consistent with the higher viral fitness in the presence of AZT and shows that these viruses are phenotypically different from WT HIV-1. Our study emphasizes the need for clinical studies to better define the impact of these mutants on treatment responses and evolution of resistance.

Anti-HIV Agents↗

PubMed2003

Predicting demographic group structures based on DNA sequence data.

The ability to infer relationships between groups of sequences, either by searching for their evolutionary history or by comparing their sequence similarity, can be a crucial step in hypothesis testing. Interpreting relationships of human immunodeficiency virus type 1 (HIV-1) sequences can be challenging because of their rapidly evolving genomes, but it may also lead to a better understanding of the underlying biology. Several studies have focused on the evolution of HIV-1, but there is little information to link sequence similarities and evolutionary histories of HIV-1 to the epidemiological information of the infected individual. Our goal was to correlate patterns of HIV-1 genetic diversity with epidemiological information, including risk and demographic factors. These correlations were then used to predict epidemiological information through analyzing short stretches of HIV-1 sequence. Using standard phylogenetic and phenetic techniques on 100 HIV-1 subtype B sequences, we were able to show some correlation between the viral sequences and the geographic area of infection and the risk of men who engage in sex with men. To help identify more subtle relationships between the viral sequences, the method of multidimensional scaling (MDS) was performed. That method identified statistically significant correlations between the viral sequences and the risk factors of men who engage in sex with men and individuals who engage in sex with injection drug users or use injection drugs themselves. Using tree construction, MDS, and newly developed likelihood assignment methods on the original 100 samples we sequenced, and also on a set of blinded samples, we were able to predict demographic/risk group membership at a rate statistically better than by chance alone. Such methods may make it possible to identify viral variants belonging to specific demographic groups by examining only a small portion of the HIV-1 genome. Such predictions of demographic epidemiology based on sequence information may become valuable in assigning different treatment regimens to infected individuals.

Adolescent↗

PubMed2003

A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation.

Stavudine (d4T) and zidovudine (AZT) are thymidine analogs widely used in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected persons. Resistance to d4T is not fully understood, although the selection of AZT resistance mutations in patients treated with d4T suggests that both drugs have similar pathways of resistance. Through the analysis of genotypic changes in nine recombinant viruses cultured with d4T, we identified a new pathway for d4T resistance mediated by K65R, a mutation not selected by AZT. Passaged viruses were derived from treatment-naïve persons or HIV-1(HXB2) and had wild-type reverse transcriptase (RT) or T215C/D mutations. K65R was selected in seven viruses and was associated with a high level of enzymatic resistance to d4T-triphosphate (median, 16-fold; range, 5- to 48-fold). The role of K65R in d4T resistance was confirmed in site-directed mutants generated in three different RT backgrounds. Phenotypic assays based on recombinant single-cycle replication or a whole-virus multiple replication cycle were unable to detect d4T resistance in d4T-selected mutants with K65R but detected cross-resistance to other nucleoside RT inhibitors. Four of the six viruses that had 215C/D mutations at baseline acquired the 215Y mutation alone or in association with K65R. Mutants having K65R and T215Y replicated less efficiently than viruses that had T215Y only, suggesting that selection of T215Y in patients treated with d4T may be favored. Our results demonstrate that K65R plays a role in d4T resistance and indicate that resistance pathways for d4T and AZT may not be identical. Biochemical analysis and improved replication assays are both required for a full phenotypic characterization of resistance to d4T. These findings highlight the complexity of the genetic pathways of d4T resistance and its phenotypic expression.

Anti-HIV Agents↗

PubMed2002

HIV incidence in the United States, 1978-1999.

CONTEXT: HIV incidence measurements, which reflect recent or current transmission, are valuable for monitoring the epidemic and evaluating prevention programs. OBJECTIVES: To summarize HIV incidence patterns and trends in U.S. population groups. DATA SOURCES: Publications in English from 1980 through mid-2000. STUDY SELECTION AND STATISTICAL METHODS: We searched the literature for reports of HIV incidence in the United States. Locally weighted scatterplot smoothing was used to generate smooth curves to estimate trends in incidence. Spearman rank correlation was used to estimate the correlation coefficient between prevalence and incidence. DATA SYNTHESIS: In 74 eligible reports, HIV incidence varied widely (0.002-19.8 per 100 person-years [py]) depending on risk group. Among men who have sex with men (MSM), HIV incidence peaked in the early 1980s (5-20/100 py) and then declined but remained high during the 1990s (2-4/100 py). Among injection drug users (IDUs), incidence decreased since the mid-1980s but differed by geographic area; in the 1990s, incidence remained high in the East (1-3/100 py) but was lower in the West (<0.5/100 py). Throughout the late 1980s and 1990s, incidence was low and stable in broader populations (blood donors: <0.01/100 py; military personnel: 0.01-0.07/100 py). The correlation between HIV incidence and prevalence was strong in populations with a prevalence less than 1% (r = 0.94, p<.0001), moderate in populations with a prevalence from 1% to less than 10% (r = 0.57, p<.0001), and weak in populations with a prevalence at least 10% (r = 0.23, p=.09). CONCLUSIONS: HIV prevention in the United States should continue to focus on MSM and IDUs. HIV incidence measurements should be considered for monitoring HIV transmission in MSM, IDUs, and other populations in which seroprevalence is high.

Adolescent↗

PubMed2002

HIV seroincidence among patients at clinics for sexually transmitted diseases in nine cities in the United States.

Although the numbers of newly reported diagnoses of AIDS decreased in the 1990s, it is not clear whether they reflect a decreasing number of new HIV infections. Direct measurement of HIV incidence through follow-up cohort studies is difficult and costly. We estimated HIV incidence and trends in incidence among men who have sex with men (MSM) and heterosexual men and women at clinics for sexually transmitted diseases (STDs) by using a recently developed serologic testing algorithm that requires only a single blood specimen. Cross-sectional anonymous serosurveys were conducted at 13 STD clinics in nine cities in the United States from 1991 through 1997. Before anonymous HIV testing, demographic and clinical information was abstracted. Of 129,774 specimens tested, 362 (0.28%) were from persons estimated to be recently infected. Incidence among MSM was 7.1% (95% confidence interval (CI): 4.8-10.3), 14 times higher than that among heterosexuals, which was 0.5% (CI: 0.4- 0.7). Incidence among MSM and heterosexuals remained unchanged during the time studied. Decreasing rates of new AIDS diagnoses in the 1990s do not reflect stable rates of new HIV infections among MSM and heterosexual patients attending these clinics.

Adult↗

PubMed2002

Comparative analysis of two commercial phenotypic assays for drug susceptibility testing of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) isolates from 50 plasma specimens were analyzed for phenotypic susceptibility to licensed reverse transcriptase inhibitors and protease inhibitors by the Antivirogram and PhenoSense HIV assays. Twenty of these specimens were from recently seroconverted drug-naïve persons, and 30 were from patients who were the sources of occupational exposures to HIV-1; 16 of the specimens in the latter group were from drug-experienced patients. The phenotypic results of the Antivirogram and PhenoSense HIV assays were categorized as sensitive or reduced susceptibility on the basis of the cutoff values established by the manufacturers of each assay. Data for 12 to 15 drugs were available by both assays for 38 specimens and represented a total of 529 pairs of results. The two data sets had a 91.5% concordance by phenotypic category. The discordant results (n = 45) were distributed randomly among 26 specimens and included 28 results (62.2%) which were within a twofold difference of the assay cutoff values. None of the discordant results were associated with primary resistance mutations that predicted high-level (>20-fold) resistance. Discordant results were distributed equally among specimens from drug-experienced and drug-naïve individuals and were slightly higher for protease inhibitors than for nonnucleoside reverse transcriptase inhibitors or nucleoside reverse transcriptase inhibitors. The findings of the present study demonstrate that the results of the Antivirogram and PhenoSense HIV assays correlate well, despite the use of different testing strategies.

Anti-HIV Agents↗

PubMed2002

Unrecognized HIV infection among patients attending sexually transmitted disease clinics.

OBJECTIVES: This study examined voluntary HIV testing rates in sexually transmitted disease (STD) clinics. METHODS: Anonymous, unlinked surveys of HIV seroprevalence and medical chart abstractions were conducted in 28 STD clinics in 14 US cities in 1997. RESULTS: Among the 52 260 patients included in the anonymous HIV serosurveys, voluntary HIV testing rates by clinic ranged from 30% to 99% (median = 58%). Patients not tested were more likely to be HIV infected than were patients who were tested, even after those with documented HIV infection were excluded, regardless of demographic characteristics, risk group, or STD diagnosis. CONCLUSIONS: HIV infection is unrecognized in substantial numbers of patients with HIV infection visiting STD clinics. Efforts are needed to increase HIV testing and counseling of all patients visiting these clinics.

AIDS Serodiagnosis↗

PubMedDate not supplied

Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000.

CONTEXT: In the United States, young people aged 15-24 represent 25% of the sexually experienced population. However, the incidence and prevalence of sexually transmitted diseases (STDs) among this age-group are unknown. METHODS: Data from a variety of sources were used to estimate the incidence and prevalence of STDs among 15-24-year-olds in the United States in 2000. The quality and reliability of the estimates were categorized as good, fair or poor, depending on the quality of the data source. RESULTS: Approximately 18.9 million new cases of STD occurred in 2000, of which 9.1 million (48%) were among persons aged 15-24. Three STDs (human papillomavirus, trichomoniasis and chlamydia) accounted for 88% of all new cases of STD among 15-24-year-olds. CONCLUSIONS: These estimates emphasize the toll that STDs have on American youth. More representative data are needed to help monitor efforts at lowering the burden of these infections.

Adolescent↗