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

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

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

Association of ‘(tropical) ataxic neuropathy’ with HTLV-II

Jamaican Neuropathy of the ataxic type (tropical ataxic neuropathy [TAN] and spastic type (tropical spastic paraparesis [TSP]) have been recognized for over a century in Jamaica. The recent association of TSP with HTLV-I (TSP/HAM) is now well established. We now present evidence for a possible association between a TAN-like illness with HTLV-II in four females aged 34–49. All presented with ataxic gait and all four have prominent mental changes. Three of the four also have minor motor deficits with urinary frequency and two have nocturnal leg cramps. All have serum antibody and all had PCR evidence of HTLV-II infection. Antibody to HTLV-II is present in CSF from two subjects. The distinctive picture of prominent ataxia and altered mental status in these subjects contrasts with a predominantly myelopathic picture seen in TSP/HAM

Demographic and clinical characteristics of the study population (N = 112).

<p>Note: HAART: highly active antiretroviral therapy. IQR: interquartile range. CD4+ lymphocyte count nadir: the lowest CD4+ lymphocyte count while in care. ADE: AIDS-defining event. IDU: history of injection drug use as a risk factor for HIV infection acquisition. HCV: hepatitis C virologic status prior to first HAART initiation. NA: not available. ART: antiretroviral therapy. PI: protease inhibitor. NNRTI: non-nucleoside reverse transcriptase inhibitor.</p>*<p>The reference group.</p>a<p>Continuous data were compared by Kruskal-Wallis test. Categorical data were compared by 2-sided Fisher's exact test.</p

Flow chart for patient selection.

<p>HAART: Highly active antiretroviral therapy.</p

Unadjusted HIV-1 RNA change.

<p>Unadjusted HIV-1 RNA following first HAART initiation for each woman (gray lines) and average decline (solid black line) by timing of HAART initiation.</p

Estimated rate of HIV-1 RNA and CD4+ lymphocyte change.

<p>The estimated rate of HIV-1 RNA decline and CD4+ lymphocyte increase (small circles) and 95% confidence interval (vertical bars) by pregnancy group over the 6 months following HAART initiation, adjusted for baseline CD4+ lymphocyte count and HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, prior ADE, prior use of non-HAART ART, HAART type, prior pregnancies, and date of HAART start. Horizontal lines represent <i>p-</i>values in a pair-wise comparison (women who started HAART during pregnancy as a reference). Left panel: The estimated rate of HIV-1 RNA decline: −0.32 log₁₀ copies/mL (95% CI −1.45, 0.81) in women who started HAART before pregnancy, −0.35 log₁₀ copies/mL (95% CI −0.57, −0.13) in women who started HAART during pregnancy, and 0.10 log₁₀ copies/mL (95% CI −0.46, 0.66) in women who started HAART after pregnancy. Right panel: The estimated rate of CD4+ lymphocyte increase: estimates were 155.8 cells/mm³ (95% CI −107.6, 419.2) in women who started HAART before pregnancy, 183.8 cells/mm³ (95% CI 110.8, 256.9) in women who started HAART during pregnancy, and −70.8 cells/mm³ (95% CI −326.8, 185.3) in women who started HAART after pregnancy.</p

Unadjusted CD4+ lymphocyte count change.

<p>Unadjusted CD4+ lymphocyte count following first HAART initiation for each woman (gray lines) and average increase (solid black line) by timing of HAART initiation.</p