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Biomedical subjects

Eric S Daar

Publications and source records attributed to Eric S Daar.

At least 19 recordsLinked to original sources
PubMed2026

Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution.

Interferon resistance has been implicated in SARS-CoV-2 escape from innate immunity, but exogenous interferon's impact on viral evolution and diversity is unknown. SNG001, an inhaled interferon-β1a treatment, was evaluated in the ACTIV-2/A5401 randomized controlled trial of therapeutics for COVID-19. We measured viral kinetics and performed whole-genome sequencing on longitudinal nasal swabs collected from ACTIV-2 participants who received either SNG001 or placebo to assess viral sequence diversity. No difference in nasal viral load decay was detected between study arms when stratifying by SARS-CoV-2 variant or by viral culture conversion. Compared to placebo participants, the SNG001-treated participants displayed significantly lower nonsynonymous amino acid average pairwise distance, indicating lower sequence diversity. Similarly, SNG001-treated individuals also developed numerically fewer nonsynonymous mutations during their infection in ORF1a, ORF1b, Spike, and Nucleocapsid. No specific emerging SARS-CoV-2 nonsynonymous amino acid changes indicating signatures of viral escape were enriched in those receiving SNG001. These in vivo data provide an intriguing signal that exogenous interferon-β1a may restrict SARS-CoV-2 viral diversity and add to growing evidence that interferon levels play a critical role in antiviral responses during COVID-19.IMPORTANCESARS-CoV-2 encodes several genes which can antagonize the interferon signaling cascade, preventing it from activating antiviral responses and thereby facilitating viral establishment and dissemination. It is unknown how the administration of exogenous interferon might affect viral evolution and immune escape. ACTIV-2/A5401 represents a unique opportunity to study the virologic effects of interferon treatment in a rigorous randomized, placebo-controlled clinical trial setting. Our characterization of longitudinal nasal samples shows that interferon-treated individuals had lower viral diversity and no evidence of viral escape mutations.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04518410.

Humans↗
PubMed2007

Unprotected anal intercourse and substance use before and after HIV diagnosis among recently HIV-infected men who have sex with men.

OBJECTIVE: The objective of this study was to assess associations between unprotected anal intercourse (UAI) and substance use before and after HIV diagnosis among recently HIV-infected MSM. STUDY DESIGN: Two hundred seven MSM completed computer-assisted self-interviews regarding type and timing of sexual activity and substance use with their last 3 partners. Date of HIV diagnosis was extracted from medical records. Generalized estimating equations, including interaction terms, were used to assess associations between substance use and UAI before and after HIV diagnosis. RESULTS: Among partners with whom sexual activity occurred before diagnosis, UAI was associated with methamphetamine use alone (odds ratio = 7.12) and a combination of methamphetamine and other substances (odds ratio = 4.06). However, after HIV diagnosis, UAI was associated with use of substances other than methamphetamine (odds ratio = 3.36), but not methamphetamine alone. CONCLUSIONS: Use of illicit substances may be differentially associated with UAI based on knowledge of HIV status and could have implications for prevention of HIV transmission.

Adolescent↗
PubMed2006

Characteristics of recently HIV-infected men who use the Internet to find male sex partners and sexual practices with those partners.

OBJECTIVE: To examine (1) characteristics of recently HIV-infected men who have sex with men (MSM) who find sex partners through the Internet and (2) differences in characteristics of and sexual behaviors practiced with Internet partners as compared to other partner types. METHODS: From May 2002 to 2005, a computer-assisted self-interview was administered to 194 recently HIV-infected MSM in southern California. MSM who used the Internet to find sex partners were compared with those who did not report Internet use, and partners found from the Internet were compared with those who were found from other venues using chi analyses, t tests, logistic regression, and generalized estimating equations. RESULTS: Seventy percent of participants reported using the Internet to find partners in the prior 3 months. In multivariate analysis, Internet users as compared to non-Internet users reported higher education levels (some college vs. high school: odds ratio [OR] = 5.04; P < 0.01 and college or greater vs. high school: OR = 9.61; P = 0.01), were more likely to be white (OR = 2.16; P = 0.04), reported more partners in the prior 3 months (OR = 1.05; P = 0.04), were more likely to have had sexual contact with all their last 3 partners after HIV diagnosis (OR = 3.43; P < 0.01), and were more likely to report that all their last 3 partners were HIV-negative (OR = 3.35; P = 0.02), but none were main partners (OR = 2.36; P = 0.02). When compared with partners who were found in other venues, Internet partners were less likely to be main partners (OR = 0.52; P < 0.01) and were more likely to be younger (OR = 0.98; P = 0.05), to be HIV-negative (OR = 1.88; P = 0.02), and to become sex partners after HIV diagnosis (OR = 1.58; P = 0.03). CONCLUSIONS: The Internet is a popular venue for recently HIV-infected MSM to find partners, many of whom are HIV-negative. Because finding sex partners through the Internet occurs after HIV diagnosis, the Internet could be a valuable target for new HIV prevention strategies.

Adult↗
PubMed2006

Unprotected anal intercourse and substance use among men who have sex with men with recent HIV infection.

OBJECTIVES: To examine within-subjects and combined between- and within-subjects associations between substance use and unprotected anal intercourse (UAI) among men who have sex with men (MSM) with recent HIV infection. METHODS: One hundred ninety-four MSM who were recently infected with HIV completed a computer-assisted questionnaire regarding sexual behaviors and substance use with their last 3 partners. Associations between UAI and substance use were assessed using conditional logistic regression (CLR) to assess associations among the 116 MSM reporting UAI with some but not all partners and generalized linear mixed effects models (GLMMs) to examine a combination of within- and between-subjects associations in the entire sample (N = 194). RESULTS: In multivariate CLR models and GLMMs, UAI was associated with the use of methamphetamine (odds ratio [OR] = 4.9 and OR = 3.5, respectively), marijuana (OR = 4.0 and OR = 2.2, respectively) and erectile dysfunction medications (EDMs) when used with a main partner (OR = 13.8 and OR = 10.1, respectively). CONCLUSIONS: Results indicate that a direct association may exist between specific substances and UAI and provide evidence that the use of methamphetamine and EDMs may contribute to HIV transmission.

Adult↗
PubMed2006

Greater CD4 T-cell gains after one year of antiretroviral therapy are associated with lower HIV-1 pol replication capacity.

We sought to determine whether pretreatment low pol replication capacity (polRC) is associated with CD4 T-cell count gains during antiretroviral therapy (ART). Patients were recruited at north American and Australian sites. Viral polRC was measured before starting ART in all subjects. We examined 243 individuals for a median 260 days after initiating ART. Low baseline polRC was associated with greater CD4 T-cell gains independent of virological responses.

Anti-HIV Agents↗
PubMed2006

Hepatitis C infection in dialysis patients: a link to poor clinical outcome?

Among the 350,000 maintenance dialysis patients in the USA, the mortality rate is high (20-23% per year) as is the prevalence of hepatitis C virus (HCV) infection (5-15%). An additional same number of dialysis patients in the USA may be infected with HCV but have undetectable HCV antibodies. Almost half of all deaths in dialysis patients, including HCV-infected patients, are due to cardiovascular disease. Since over two-thirds of dialysis patients die within 5 years of initiating dialysis and because markers of malnutrition-inflammation complex syndrome (MICS), rather than traditional cardiovascular risk factors, are among the strongest predictors of early death in these patients, the impact of HCV infection on nutritional status and inflammation may be a main cause of poor survival in this population. Based on data from our cross-sectional and limited longitudinal studies, we hypothesize that HCV infection confounds the association between MICS and clinical outcomes in dialysis patients and, by doing so, leads to higher short-term cardiovascular events and death. Understanding the natural history of HCV and its association with inflammation, nutrition and outcomes in dialysis patients may lead to testing more effective anti-HCV management strategies in this and other similar patient populations, providing benefits not only for HCV infection but the detrimental consequences associated with this infection. In this article, we review the link between the HCV infection and mortality in dialysis patients and compare HCV antibody to molecular methods to detect HCV infection in these individuals.

Cachexia↗
PubMed2006

Lack of neutralizing antibody response to HIV-1 predisposes to superinfection.

Occurrences of HIV-1 superinfection offer a unique opportunity to investigate the correlates of immune protection. Here we describe the neutralizing antibody responses of a cohort of recently infected individuals who were screened for HIV superinfection. Three individuals identified with HIV superinfection had less cross-protective and autologous neutralizing antibody response than their non-superinfected case-controls. Neutralizing antibody may be crucial in the protection against superinfection and may explain why superinfection has only been documented following recent infection or treatment interruption. These data have considerable implications for vaccine development.

Adult↗
PubMed2006

Cognitive-behavioral intervention to enhance adherence to antiretroviral therapy: a randomized controlled trial (CCTG 578).

OBJECTIVE: We conducted a randomized, multi-site, controlled trial of a cognitive-behavioral adherence intervention for patients initiating or changing an antiretroviral (ART) regimen. DESIGN: A 3 x 2 factorial design was used with the primary randomization assigning patients (1: 1: 1) to one of two adherence interventions or usual care. METHODS: The five-session adherence interventions consisted of cognitive-behavioral and motivational components, with or without a 2-week pre-treatment placebo practice trial. Intent-to-treat analysis used probability weights and regression tree analysis to account for missing data. RESULTS: A total of 230 patients were randomized; 199 started ART, of whom 74% completed the 48-week study. Electronic monitored adherence outcomes between the two intervention groups did not differ significantly and were thus pooled in analyses. At week 4, 82% of intervention patients had taken at least 90% of their prescribed ART doses, compared with 65% of controls (P < 0.01); this group difference dropped to 12% at week 12 (72 versus 60%; P = 0.15) and 11% at week 24 (66 versus 55%; P = 0.28). Mean adherence in the intervention group was significantly higher than the control group at week 24 (89 versus 81%; P < 0.05) only. There were no group differences with respect to HIV-1 RNA throughout the study. CONCLUSIONS: The effects of the cognitive-behavioral intervention on adherence were modest and transient, and no effects were observed on viral load or CD4 cell count. More robust effects may require a more intense intervention that combines ongoing adherence monitoring and individualized intervention "dosage" that matches the need and performance of each patient.

Adult↗
PubMed2006

Molecular analysis of HIV strains from a cluster of worker infections in the adult film industry, Los Angeles 2004.

OBJECTIVES: In April 2004, 13 susceptible women were exposed to a single acutely HIV-1-infected man while employed to perform various sex acts for the production of adult films; three women were subsequently found to have acquired HIV infection (23% attack rate). As part of the investigation of this infection cluster, we evaluated whether viral strains collected from infected individuals were significantly related. METHODS: We determined nucleotide sequences from the C2V3C3 and gp41 region of env and the p17 region of gag in viruses from the three infected individuals from whom specimens were available. We then compared these sequences phylogenetically to comparable sequences from available reference strains. Genotypic and phenotypic antiretroviral drug resistance was determined for plasma virus from the male index case and one female contact at a separate commercial laboratory. RESULTS: The env and gag sequences of the HIV strains from the male index case and two of the infected women were 100% similar. Genotyping of the male index case's virus identified 12 mutations, which represented known naturally occurring polymorphisms in the subtype B consensus sequence that are not associated with antiretroviral drug resistance. Genotyping of the virus from the female contact identified 10 mutations, all of which were shared by the virus from the male index case. Phenotyping demonstrated that both viruses were susceptible to all antiretroviral drugs tested. CONCLUSION: Molecular and virological data strongly support the epidemiological conclusion that these women were infected with an identical strain of HIV through occupational exposure to an individual with an acute HIV infection.

Cluster Analysis↗
PubMed2006

Novel antiretroviral agents in HIV therapy.

There are many promising new agents in development for the treatment of HIV type 1 (HIV-1). The targets of antiretroviral drugs include the three major HIV-1 enzymes (reverse transcriptase, protease, and integrase), final packaging and export of mature virions, and entry mediated by the CD4 receptor and the CCR5 and CXCR4 coreceptors. Drugs in development in existing classes are primarily designed to provide new options for those with resistance to existing agents. Novel agents such as those targeting integrase, entry inhibitors, and those targeting viral processing likely will be useful the treatment of antiretroviral-experienced patients. Depending on safety, efficacy, tolerability, and convenience of dosing, new agents may also alter the current treatment paradigms for first-line therapy. This review summarizes data on several drugs that could move forward into the clinical arena and affect the lives of those infected with HIV-1.

Journal Article↗
PubMed2006

Human immunodeficiency virus and fertility care: embarking on a path of knowledge and access.

The convergence of medical and social factors in the HIV-infected community has produced a growing interest in procreation with the aid of assisted reproductive technologies. Meeting the needs of fertile and infertile, concordant and discordant couples will require the establishment of multidisciplinary treatment centers and research programs to define and provide the safest and most effective therapy possible.

HIV Infections↗
PubMed2006

Transmission behaviors of recently HIV-infected men who have sex with men.

OBJECTIVES: Analyze postdiagnosis behaviors of recently HIV-infected men who have sex with men (MSM). METHODS: Recently HIV-infected MSM were interviewed at 6 weeks (n = 153) and 3 months (n = 113) after diagnosis. Behaviors from baseline to follow-up were compared; multivariate logistic regression identified associations between baseline characteristics and behavior at follow-up. RESULTS: At follow-up, MSM reported a significantly lower mean of partners (7.9 vs. 5.2) and lower means of 1-time (1.9 vs. 0.8), unknown (3.7 vs. 2.6), and acquaintance (1.1 vs. 0.5) partners than at baseline. In multivariate analyses, unprotected anal intercourse (UAI) with the last partner at follow-up was more likely if the last partner at baseline was a main partner (odds ratio [OR] = 2.94, 95% confidence interval [CI]: 1.04 to 8.33) or HIV-positive partner (OR = 3.36, 95% CI: 1.27 to 8.88) but less likely if, at follow-up, the last partner was HIV-negative (OR = 0.28, 95% CI: 0.08 to 1.00) or of unknown HIV status (OR = 0.23, 95% CI: 0.08 to 0.71), the participant had a history of nonconsensual sex (OR = 0.25, 95% CI: 0.09 to 0.72), or the participant had more than 1 partner (OR = 0.28, 95% CI: 0.09 to 0.86). More than 1 partner at follow-up was associated with no main partner at baseline or follow-up (OR = 2.76, 95% CI: 1.12 to 6.78), more partners in the last 12 months (OR = 1.02, 95% CI: 1.01 to 1.04), and UAI with the last partner (OR = 0.36, 95% CI: 0.14 to 0.90). CONCLUSIONS: After diagnosis, some but not all recently HIV-infected MSM reduced risky sexual behavior permitting potential HIV transmission.

California↗
PubMed2005

Stromal cell-derived factor-1 genotype, coreceptor tropism, and HIV type 1 disease progression.

This study used a well characterized cohort of human immunodeficiency virus type 1 (HIV-1)-infected hemophiliacs to define the relationship between the SDF1-3'A allele, the plasma HIV-1 coreceptor tropism, and the natural history of HIV-1 disease. Subjects heterozygous or homozygous for the SDF1-3'A allele experienced higher rates of decline in CD4+ T cell counts over time than did those without the allele (P=.009). Moreover, they had an increased risk of progression to acquired immunodeficiency syndrome and death, a relationship that persisted even when baseline plasma HIV-1 RNA levels and CD4+ T cell counts or CCR5 Delta 32 and CCR2-64I genotype were controlled for. This relationship was even stronger in a subgroup of subjects for whom tropism data were available. Subjects with the SDF1-3'A allele were also more likely to have detectable X4-tropic viruses (P=.012), and, when tropism was included in the survival analyses, the effect of the SDF1-3'A allele on disease progression was no longer significant. Therefore, the increased frequency of X4-tropic viruses in subjects carrying the SDF1-3'A allele may explain the observed adverse effect that this allele has on the natural history of HIV-1 disease.

Adolescent↗
PubMed2005

Longitudinal analysis of CD8 T-cell responses to HIV and hepatitis C virus in a cohort of co-infected haemophiliacs.

OBJECTIVE: To investigate CD8 T-cell responses to HIV and hepatitis C virus (HCV) over time in a group of co-infected children with haemophilia to assess the influence of the virus infections on each other and on clinical outcome. DESIGN: The HIV and HCV CD8 T-cell response of HLA-A2 co-infected individuals in the cohort were analysed at two time points, looking at the frequency and phenotype of HIV-specific T cells and assessing overall responses to the two viruses. METHODS: Peripheral blood mononuclear cells (PBMC) from 72 HLA-A2 co-infected individuals were analysed using an HIV HLA-A2 tetramer and by IFN-gamma ELISpot using a panel of HIV and HCV antigens. PBMC from a group of 26 HLA-A2 HIV mono-infected adults were also analysed as a comparison. RESULTS: We identified two distinct patterns of response: some patients had a limited response to either virus whilst others made responses to a range of HIV epitopes. HCV responses were detected only in those who made multiple responses to HIV epitopes (P<0.0001). HCV infection had an influence on the phenotype of HIV-specific CD8 T cells, with a reduction in relative perforin and CD57 expression. Lack of functional or tetramer-positive HIV-specific T cells was associated with a decline in absolute CD4 T-cell counts between the time points (up to 7 years; P = 0.005). CONCLUSION: HCV infection has an impact on the phenotype of HIV-specific CD8 T cells. In this well-defined cohort, failure to maintain effective CD8 T-cell responses against HIV may contribute to disease progression.

Adolescent↗
PubMed2005

HIV-1 pol replication capacity predicts disease progression.

OBJECTIVE: To determine the influence of pol replication capacity on the natural history of HIV-1 infection. DESIGN: Pol replication capacity was measured using a recombinant virus single cycle assay on baseline plasma specimens from subjects enrolled in the Hemophilia Growth and Development Study. SETTING: Children and adolescents with hemophilia and HIV-1 infection were enrolled at multiple sites across the USA into a natural history study. PARTICIPANTS: The Hemophilia Growth and Development Study enrolled 207 HIV-1-infected hemophiliacs between 6 and 19 years of age in 1989 and 1990. Subjects were followed every 6 months through 1997 with pol replication capacity measurements available from 128 of the subjects. MAIN OUTCOME MEASURES: A univariate model defined the relationship between pol replication capacity and HIV-1 RNA and CD4 T-cell number. A random effects model assessed the ability of this measure to predict CD4 T-cell decline over time and a Cox proportional hazards model and Kaplan-Meier analyses defined how it predicts clinical progression. RESULTS: Pol replication capacity measures correlated with baseline HIV-1 RNA, R = 0.189 (P = 0.03) and CD4 T-cell number, -0.197 (P = 0.03). It also independently predicted CD4 T-cell decline over time and progression to AIDS. CONCLUSIONS: This study demonstrates that pol replication capacity independently influences the natural history of HIV-1 infection.

Adolescent↗
PubMed2005

Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1.

Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatment.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Primary human immunodeficiency virus type 1 infection.

Primary human immunodeficiency virus type 1 (HIV-1) infection represents the initial stage of disease that immediately follows viral entry into the body. Primary infection is frequently accompanied by an acute retroviral syndrome with associated high levels of plasma HIV-1 RNA and the development of host immune responses. The identification of subjects during this period requires a high index of suspicion and an understanding of how to make the diagnosis, as standard HIV-1 antibody tests can initially be negative. Identifying these people provides a unique opportunity for early counseling to reduce further transmission, facilitates entry into care, and allows for further study of the immunopathogenesis of disease and the potential role of early antiretroviral therapy.

Anti-Retroviral Agents↗