Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy

Background Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)–based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens. Methods Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)–, and nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals. Results Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/μL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant. Conclusions Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens

Coumermycin inhibition of murine retro virus replication in cultured cells

The effect of coumermycin A, activity on the infection and replication of murine type C retroviruses was studied in vitro. The infectivity of five prototype ecotropic retroviruses was reduced by 50 to 94%, with viral titres decreased up to seven-fold. These values were substantiated by progeny production studies. Similar results were obtained with five strains of xenotropic retroviruses. Delayed inhibition of growth kinetics in mouse SC-1 cells was observed with 7-5 and 10mg/l of coumermycin A,. This effect was markedly reduced after three cycles of freezing and thawing of the drug. Changes in the absorption spectra of coumermycin A, were observed after eight cycles of freezing and thawing

Sex and Race Disparities in Mortality and Years of Potential Life Lost Among People With HIV: A 21-Year Observational Cohort Study

BACKGROUND: Since the availability of antiretroviral therapy, mortality rates among people with HIV (PWH) have decreased; however, this does not quantify premature deaths among PWH, and disparities persist. METHODS: We examined all-cause and premature mortality among PWH receiving care at the Vanderbilt Comprehensive Care Clinic from January 1998 to December 2018. Mortality rates were compared by demographic and clinical factors, and adjusted incidence rate ratios (aIRRs) were calculated using multivariable Poisson regression. For individuals who died, age-adjusted years of potential life lost (aYPLL) per total person-years living with HIV were calculated from US sex-specific life tables, and sex and race differences were examined using multivariable linear regression. RESULTS: Among 6531 individuals (51% non-Hispanic [NH] White race, 40% NH Black race, 21% cis-gender women, 78% cis-gender men) included, 956 (14.6%) died. In adjusted analysis, PWH alive in the most recent calendar era (2014-2018) had decreased risk of mortality compared with those in the earliest calendar era (1998-2003; aIRR, 0.22; 95% CI, 0.17-0.29), and women had increased risk of death compared with men (aIRR, 1.31; 95% CI, 1.12-1.54). Of those who died, Black women had the highest aYPLL (aIRR, 592.5; 95% CI, 588.4-596.6), followed by Black men (aIRR, 470.7; 95% CI, 468.4-472.9), White women (aIRR, 411.5; 95% CI, 405.6-417.4), then White men (aIRR, 308.6; 95% CI, 308.0-309.2). In adjusted models, higher YPLL remained associated with NH Black race and cis-gender women, regardless of HIV risk factor. CONCLUSIONS: Despite marked improvement over time, sex disparities in mortality as well as sex and race disparities in YPLL remained among PWH in this cohort

The relationship between adverse neighborhood socioeconomic context and HIV continuum of care outcomes in a diverse HIV clinic cohort in the Southern United States

Retention in care and viral suppression are critical to delaying HIV progression and reducing transmission. Neighborhood socioeconomic context (NSEC) may affect HIV care receipt. We therefore assessed NSEC's impact on retention and viral suppression in a diverse HIV clinical cohort. HIV-positive adults with ≥1 visit at the Vanderbilt Comprehensive Care Clinic and 5-digit ZIP code tabulation area (ZCTA) information between 2008 and 2012 contributed. NSEC z-score indices used neighborhood-level socioeconomic indicators for poverty, education, labor-force participation, proportion of males, median age, and proportion of residents of black race by ZCTA. Retention was defined as ≥2 HIV care visits per calendar year, >90 days apart. Viral suppression was defined as an HIV-1 RNA <200 copies/mL at last measurement per calendar year. Modified Poisson regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI). Among 2272 and 2541 adults included for retention and viral suppression analyses, respectively, median age and CD4 count at enrollment were approximately 38 (1st and 3rd quartile: 30, 44) years and 351 (176, 540) cells/μL, respectively, while 24% were female, and 39% were black. Across 243 ZCTAs, median NSEC z-score was 0.09 (-0.66, 0.48). Overall, 79% of person-time contributed was retained and 74% was virally suppressed. In adjusted models, NSEC was not associated with retention, though being in the 4th vs. 1st NSEC quartile was associated with lack of viral suppression (RR = 0.88; 95% CI: 0.80-0.97). Residing in the most adverse NSEC was associated with lack of viral suppression. Future studies are needed to confirm this finding

Psychosocial Characteristics and Sexual Behaviors of People in Care for HIV Infection: An Examination of Men Who Have Sex with Men, Heterosexual Men and Women

Few studies have examined the psychosocial factors associated with sexual transmission behaviors among HIV-positive men who have sex with men (MSM), heterosexual men (MSW) and women. We enrolled 1,050 sexually active HIV-positive patients at seven HIV clinics in six US cities as part of a clinic-based behavioral intervention. We describe the sexual transmission behaviors and examine demographic, clinical, psychosocial, and clinic prevention variables associated with unprotected anal or vaginal intercourse (UAVI). Twenty-three percent of MSM, 12.3% of MSW and 27.8% of women engaged in UAVI with partners perceived to be HIV-negative or of unknown serostatus. Among MSM and MSW, having multiple partners and lower self-efficacy were associated with increased odds of UAVI. Self-rating one’s health status as excellent/very good was a risk factor for UAVI among MSM. Among women, binge drinking and stressful life events were associated with UAVI. These findings identify variables that warrant attention in targeted interventions

Keck Planet Finder: design updates

The Keck Planet Finder (KPF) is a fiber-fed, high-resolution, high-stability spectrometer in development at the UC Berkeley Space Sciences Laboratory for the W.M. Keck Observatory. KPF is designed to characterize exoplanets via Doppler spectroscopy with a goal of a single measurement precision of 0.3 m s-1 or better, however its resolution and stability will enable a wide variety of astrophysical pursuits. Here we provide post-preliminary design review design updates for several subsystems, including: the main spectrometer, the fabrication of the Zerodur optical bench; the data reduction pipeline; fiber agitator; fiber cable design; fiber scrambler; VPH testing results and the exposure meter

Keck Planet Finder: design updates

The Keck Planet Finder (KPF) is a fiber-fed, high-resolution, high-stability spectrometer in development at the UC Berkeley Space Sciences Laboratory for the W.M. Keck Observatory. KPF is designed to characterize exoplanets via Doppler spectroscopy with a goal of a single measurement precision of 0.3 m s-1 or better, however its resolution and stability will enable a wide variety of astrophysical pursuits. Here we provide post-preliminary design review design updates for several subsystems, including: the main spectrometer, the fabrication of the Zerodur optical bench; the data reduction pipeline; fiber agitator; fiber cable design; fiber scrambler; VPH testing results and the exposure meter

Antiretroviral Therapy Initiation Before, During, or After Pregnancy in HIV-1-Infected Women: Maternal Virologic, Immunologic, and Clinical Response

Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.We conducted a retrospective cohort study from 1997–2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30).0.01). There were no statistical differences in rates of HIV disease progression between groups.HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy

CD4+/CD8+ ratio, age, and risk of serious noncommunicable diseases in HIV-infected adults on antiretroviral therapy

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