A new frailty syndrome: Central obesity and frailty in older adults with the human immunodeficiency virus

Objectives To evaluate the relationships between body composition and physical frailty in community-dwelling older adults with the human immunodeficiency virus (HIV) (HOA). Design Cross-sectional. Setting Academic hospital-based infectious disease clinic in Rochester, New York. Participants Forty community-dwelling HOA aged 50 and older undergoing antiretroviral therapy who were able to ambulate without assistive devices with a mean age of 58, a mean BMI of 29.0 kg/m , mean CD4 count of 569 cells/mL, and a mean duration since HIV diagnosis of 17 years; 28% were female and 57% Caucasian. Measurements Subjective and objective measures of functional status were evaluated using the Physical Performance Test (PPT), the graded treadmill test, knee strength, gait speed, balance, and the Functional Status Questionnaire (FSQ). Body composition was evaluated using dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). Results Sixty percent (25/40) of the participants met standard criteria for physical frailty. Frail (FR) and nonfrail (NF) participants were comparable in age, sex, CD4 count, and viral load. FR HOA had greater impairments in PPT, peak oxygen uptake, FSQ, walking speed, balance, and muscle quality than NF HOA. FR HOA had a greater body mass index (BMI), fat mass, and truncal fat with lipodystrophy. Moreover, PPT score was inversely related to trunk fat (correlation coefficient (r) = -0.34; P =.04) and ratio of intermuscular fat to total fat (r = -0.60; P =.02) after adjusting for covariates. Conclusion HOA represent an emerging cohort of older adults who frequently experience frailty at a much younger age than the general older population. Central obesity and fat redistribution are important predictors of frailty in community-dwelling HOA. These findings suggest that physical frailty in HOA may be amenable to lifestyle interventions, especially exercise and diet therapy. © 2012, The American Geriatrics Society.

Depot Medroxyprogesterone Acetate in Combination with a Twice-Daily Lopinavir-Ritonavir-Based Regimen in HIV-Infected Women Showed Effective Contraception and a Lack of Clinically Significant Interactions, with Good Safety and Tolerability: Results of the ACTG 5283 Study

We conducted an open-label, steady-state pharmacokinetic (PK) study of drug-drug interactions between depot medroxyprogesterone acetate (DMPA) and twice-daily lopinavir (LPV) plus low-dose ritonavir (RTV) (LPV/r) among 24 HIV-infected women and compared the results to those for HIV-infected women receiving DMPA while on no antiretroviral therapy or on nucleosides only (n = 14 subjects from the control arm of AIDS Clinical Trials Group [ACTG] study 5093). The objectives of the study were to address the effect of LPV/r on DMPA and to address the effect of DMPA on LPV/r therapy. PK parameters were estimated using noncompartmental analysis with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of LPV and RTV PKs before and 4 weeks after DMPA dosing. Plasma progesterone concentrations were measured every 2 weeks after DMPA dosing through week 12. Although the MPA area under the concentration-time curve and maximum concentration of drug in plasma were statistically significantly increased in the study women on LPV/r compared to those in the historical controls, these increases were not considered clinically significant. There were no changes in LPV or RTV exposure after DMPA. DMPA was well tolerated, and suppression of ovulation was maintained. (This study has been registered at ClinicalTrials.gov under registration no. NCT01296152.)

Associations Between Genital Tract Infections, Genital Tract Inflammation, and Cervical Cytobrush HIV-1 DNA in US Versus Kenyan Women

Cervical shedding of HIV-1 DNA may influence HIV-1 sexual transmission. HIV-1 DNA was detected in 250 (80%) of 316 and 207 (79%) of 259 cervical cytobrush specimens from 56 US and 80 Kenyan women, respectively. Plasma HIV-1 RNA concentration was associated with increased HIV-1 DNA shedding among US and Kenyan women. Kenyan women had higher cervicovaginal concentrations of proinflammatory interleukins (IL)-1β, IL-6, IL-8, and anti-inflammatory secretory leukocyte protease inhibitor compared with US women (all P < 0.01). HIV-1 DNA shedding was associated with increased concentrations of IL-1β and IL-6 and lower secretory leukocyte protease inhibitor among US women but not Kenyan women

The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy

ObjectiveTo assess whether CD8 T-cell activation predicts risk of AIDS and non-AIDS morbidity during suppressive antiretroviral treatment (ART).DesignPost-hoc analyses of ART-naive participants in prospective ART studies. Participants with HIV-RNA levels 200 copies/ml or less and CD8 T-cell activation data (%CD38HLA-DR) at year-1 of ART were selected to determine years 2-5 incidence of AIDS and non-AIDS events.MethodsWe censored data at time of ART interruption or virologic failure. Inverse probability of censoring-weighted logistic regression was used to correct for informative censoring.ResultsWe included 1025 participants; 82% were men, median age 38 years, pre-ART CD4 cell count 255 cells/μl, and year-1-activated CD8 T cells 24%. Of these, 752 had 5 years of follow-up; 379 remained on ART and had no confirmed plasma HIV-RNA more than 200 copies/ml. The overall probability of an AIDS or non-AIDS event in years 2-5 was estimated at 13% [95% confidence interval (CI) 10-15%] had everyone remained on suppressive ART. Higher year-1-activated CD8 T-cell percentage increased the probability of subsequent events [odds ratio 1.22 per 10% higher (95% CI 1.04-1.44)]; this effect was not significant after adjusting for age. Among those age 50 years at least (n=108 at year 1), the probability of an event in years 2-5 was 37% and the effect of CD8 T-cell activation was more apparent (odds ratio=1.42, P=0.02 unadjusted and adjusted for age).ConclusionCD8 T-cell activation is prognostic of clinical events during suppressive ART, although this association is confounded by age. The consequences of HIV-associated immune activation may be more important in patients 50 years and older

Antiretroviral Resistance and Pregnancy Characteristics of Women with Perinatal and Nonperinatal HIV Infection

Objective. To compare HIV drug resistance in pregnant women with perinatal HIV (PHIV) and those with nonperinatal HIV (NPHIV) infection. Methods. We conducted a multisite cohort study of PHIV and NPHIV women from 2000 to 2014. Sample size was calculated to identify a fourfold increase in antiretroviral (ARV) drug resistance in PHIV women. Continuous variables were compared using Student’s t-test and Wilcoxon rank-sum tests. Categorical variables were compared using χ2 and Fisher’s exact tests. Univariate analysis was used to determine factors associated with antiretroviral drug resistance. Results. Forty-one PHIV and 41 NPHIV participants were included. Women with PHIV were more likely to have drug resistance than those with NPHIV ((55% versus 17%, p=0.03), OR 6.0 (95% CI 1.0–34.8), p=0.05), including multiclass resistance (15% versus 0, p=0.03), and they were more likely to receive nonstandard ARVs during pregnancy (27% versus 5%, p=0.01). PHIV and NPHIV women had similar rates of preterm birth (11% versus 28%, p=0.08) and cesarean delivery (47% versus 46%, p=0.9). Two infants born to a single NPHIV woman acquired HIV infection. Conclusions. PHIV women have a high frequency of HIV drug resistance mutations, leading to nonstandard ARVs use during pregnancy. Despite nonstandard ARV use during pregnancy, PHIV women did not experience increased rates of adverse pregnancy outcomes

Interaction Between Lactobacilli, Bacterial Vaginosis-Associated Bacteria, and HIV Type 1 RNA and DNA Genital Shedding in U.S. and Kenyan Women

Bacterial vaginosis has been associated with genital HIV-1 shedding; however, the effect of specific vaginal bacterial species has not been assessed. We tested cervicovaginal lavage from HIV-1-seropositive women for common Lactobacillus species: L. crispatus, L. jensenii, and seven BV-associated species: BVAB1, BVAB2, BVAB3, Leptotrichia, Sneathia, Megasphaera, and Atopobium spp. using quantitative PCR. We used linear and Poisson regression to evaluate associations between vaginal bacteria and genital HIV-1 RNA and DNA. Specimens from 54 U.S. (310 visits) and 50 Kenyan women (137 visits) were evaluated. Controlling for plasma viral load, U.S. and Kenyan women had similar rates of HIV-1 RNA (19% of visits vs. 24%; IRR=0.95; 95% CI 0.61, 1.49) and DNA shedding (79% vs. 76%; IRR=0.90; 0.78, 1.05). At visits during antiretroviral therapy (ART), the likelihood of detection of HIV-1 RNA shedding was greater with BVAB3 (IRR=3.16; 95% CI 1.36, 7.32), Leptotrichia, or Sneathia (IRR=2.13; 1.02, 4.72), and less with L. jensenii (IRR=0.39; 0.18, 0.84). At visits without ART, only L. crispatus was associated with a lower likelihood of HIV-1 RNA detection (IRR=0.6; 0.40, 0.91). Vaginal Lactobacillus species were associated with lower risk of genital HIV-1 shedding, while the presence of certain BV-associated species may increase that risk

Cervicovaginal Shedding of HIV Type 1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota

We examined the relationship of proinflammatory vaginal cytokines and secretory leukocyte protease inhibitor (SLPI) with genital HIV-1 shedding after controlling for genital coinfections. Fifty-seven HIV-1-infected women in Seattle, WA (n = 38) and Rochester, NY (n = 19) were followed every 3–4 months for a total of 391 visits. At each visit, plasma and cervicovaginal lavage (CVL) were tested for HIV-1 RNA using qPCR. Vaginal samples were tested for bacterial vaginosis, yeast, hydrogen peroxide-producing Lactobacillus colonization, Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, CMV, and HSV shedding. CVL interleukins (IL)-1β, IL-6, IL-8, and SLPI were measured using ELISA. Linear regression with generalized estimating equations examined effects of cytokine concentrations on CVL HIV-1 RNA, adjusted for plasma HIV RNA, and measured coinfections. CVL IL-1β and IL-8 were significantly associated with CVL HIV-1 RNA. This persisted after adjusting for plasma HIV-1 RNA. Higher levels of IL-1β were associated with higher concentrations of HIV-1 RNA in CVL (β = 0.25, 95% CI 0.09, 0.42), as were higher levels of IL-8 (β = 0.34, 95% CI 0.17, 0.50). Adjusting for the presence of the coinfections described, this relationship was attenuated for IL-1β (β = 0.16; 95% CI –0.01, 0.33) but still significant for IL-8 (β = 0.29; 95% CI 0.13, 0.45). The proinflammatory cytokines IL-1β and IL-8 are associated with higher cervicovaginal HIV-1 RNA concentrations, even after controlling for plasma viral load and vaginal microbial cofactors. This association suggests that there may be additional, noninfectious causes of inflammation that increase cervicovaginal HIV-1 shedding

Lipid-Lowering Therapy in HIV-Infected Patients: Relationship with Antiretroviral Agents and Impact of Substance-Related Disorders

The use of combination antiretroviral therapy (cART) has significantly decreased the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. Lipid disorders, including lipodystrophy, hypertriglyceridemia, and hypercholesterolemia, remain the most commonly reported metabolic disorders among those treated with long-term cART. Mounting evidence suggests an association between drug abuse and poor glycemic control and diabetes complications. Substance related disorders (SRD) may increase the risk of metabolic syndrome. The aim of this retrospective cohort study was to examine the relationship between SRD, cART, and lipid-lowering agent use in an HIV infected population. Patients received efavirenz or protease inhibitor-based cART for at least 6 months. Prescription information was retrieved from the medical records. The primary outcome was the use of lipid-lowering agents including statins, fibrates and fish oil. The impact of SRD and cART was assessed on the lipid-lowering agent use. A total of 276 subjects with HIV infection were included, 90 (33%) received lipid-lowering agents, and 31 (34%) had SRD. Smoking was prevalent among subjects with SRD (84 vs 15%, p<0.001). Statins were the mainstay for the management of dyslipidemia (66%), followed by the fibrates (24%), omega-3 fatty acids (5%), nicotinic acid (3%) and the cholesterol absorption inhibitors (3%). Use of statins or fibrates was significantly higher among subjects without SRD than those with (40 vs 23%, p=0.005). The type of cART, including efavirenz and protease inhibitors, appeared to have no significant impact on the use pattern of lipid-lowering agents. Lopinavir/ritonavir (lopinavir/r) was mostly prescribed for subjects with SRD (25 vs 8%, p=0.02). Among HIV-infected patients, statins remain the mainstay for the management of dyslipidemia in routine clinical care, followed by fibrates. A significant high risk of metabolic disorders among patients with SRD is implicated by heavy tobacco use and prevalent lopinavir/r-based treatment. Significantly low rate of lipid-lowering agent use in this population underscores the importance of lipid disorder scrutiny and cART treatment optimization for HIV-infected patients with SRD