Association Between Mid-arm Muscle Circumference and Cognitive Function: A Longitudinal Study of Chinese Adults.

BACKGROUND: Dementia affects 55 million people worldwide and low muscle mass may be associated with cognitive decline. Mid-arm muscle circumference (MAMC) correlates with dual-energy Xray absorptiometry and bioelectrical impedance analyses, yet are not routinely available. Therefore, we examined the association between MAMC and cognitive performance in older adults. METHODS: We included community-dwelling adults ≥55 years from the China Health and Nutrition Survey. Cognitive function was estimated based on a subset of the modified Telephone Interview for Cognitive Status (0-27, low-high) during years (1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, 2018). A multivariable linear mixed-effects model was used to test whether MAMC was associated with rate of cognitive decline across age groups and cognitive function overall. RESULTS: Of 3702 adults (53% female, 63.2 ± 7.3 years), mean MAMC was 21.4 cm ± 3.0 and baseline cognitive score was 13.6 points ±6.6. We found no evidence that the age-related rate of cognitive decline differed by MAMC (P = .77). Declines between 5-year age groups ranged from -.80 [SE (standard error) .18] to -1.09 [.22] for those at a mean MAMC, as compared to -.86 [.25] to -1.24 [.31] for those at a 1 MAMC 1 standard deviation above the mean. Higher MAMC was associated with better cognitive function with .13 [.06] higher scores for each corresponding 1 standard deviation increase in MAMC across all ages. CONCLUSION: Higher MAMC at any age was associated with better cognitive performance in older adults. Understanding the relationship between muscle mass and cognition may identify at-risk subgroups needing targeted interventions to preserve cognition.

III. TESTING FOR QUALITY THRESHOLDS AND FEATURES IN EARLY CARE AND EDUCATION.

In this chapter, we report on the analyses focusing on both quality thresholds and quality features. First, we address questions about quality thresholds, using two analytic approaches. The analyses ask whether there is evidence suggesting thresholds in the association between a specific quality measure and a specific child outcome. Second, we extend these analyses to ask whether each child outcome is more strongly related to global quality measures or to quality measures that measure teacher-child interactions or quality of instruction in a given content area. The research to date provides the basis for the articulation of two hypotheses related to quality thresholds and features: (1) the quality of ECE is a stronger predictor of residualized gains in child outcomes in classrooms with higher quality than in classrooms with lower quality and (2) more specific measures of quality are stronger predictors of residualized gains in child outcomes than are global measures. We turn now to analyses intended to address these hypotheses by using data from several data sets.

Association Between Weight Status and Rate of Cognitive Decline: China Health and Nutrition Survey 1997-2018.

BACKGROUND: There is a close relationship between weight status and cognitive impairment in older adults. This study examined the association between weight status and the trajectory of cognitive decline over time in a population-based cohort of older adults in China. METHODS: We used data from adults aged ≥55 years participating in the China health and nutrition survey (1997-2018). Underweight (body mass index [BMI] ≤ 18.5 kg/m2), normal weight (18.5-23 kg/m2), overweight (23-27.5 kg/m2), and obesity (BMI ≥ 27.5 kg/m2) were defined using the World Health Organization Asian cutpoints. Global cognition was estimated every 2-4 years through a face-to-face interview using a modified telephone interview for cognitive status (scores 0-27). The association between BMI and the rate of global cognitive decline, using a restricted cubic spline for age and age category, was examined with linear mixed-effects models accounting for correlation within communities and individuals. RESULTS: We included 5 992 adults (53% female participants, mean age of 62 at baseline). We found differences in the adjusted rate of global cognitive decline by weight status (p = .01 in the cubic spline model). Models were adjusted for sex, marital status, current employment status, income, region, urbanization, education status, birth cohort, leisure activity, smoking status, and self-reported diagnosis of hypertension, diabetes, or Myocardial Infarction (MI)/stroke. In addition, significant declines by age in global cognitive function were found for all weight status categories except individuals with obesity. CONCLUSIONS: In a cohort of adults in China, cognitive decline trajectory differed by weight status. A slower rate of change was observed in participants classified as having obesity.

Modeling the impact of Trichomonas vaginalis infection on HIV transmission in HIV-infected individuals in medical care.

BACKGROUND: To assess factors associated with having a Trichomonas vaginalis (TV) infection among persons receiving care for human immunodeficiency virus (HIV) and estimate the number of transmitted HIV infections attributable to TV. METHODS: HIV clinic patients were recruited from 2 secondary prevention studies, screened by urine nucleic-acid amplification tests for sexually transmitted infections, and interviewed about risk factors (baseline, 6, and 12 months). We conducted mathematical modeling of the results to estimate the number of transmitted HIV infections attributable to TV among a cohort of HIV-infected patients receiving medical care in North Carolina. RESULTS: TV was prevalent in 7.4%, and incident in 2% to 3% of subjects at follow-up. Individuals with HIV RNA <400 copies/mL (odds ratio, 0.32; 95% CI: 0.14-0.73) and at least 13 years of education (odds ratio, 0.24; 95% CI: 0.08-0.70) were less likely to have TV. Mathematical modeling predicted that 0.062 HIV transmission events occur per 100 HIV-infected women in the absence of TV infection and 0.076 HIV infections per 100 HIV- and TV-infected women (estimate range: 0.070-0.079), indicating that 23% of the HIV transmission events from HIV-infected women may be attributable to TV infection when 22% of women are coinfected with TV. CONCLUSIONS: The data suggest the need for improved diagnosis of TV infection and suggest that HIV-infected women in medical care may be appropriate targets for enhanced testing and treatment.

Genital tract, cord blood, and amniotic fluid exposures of seven antiretroviral drugs during and after pregnancy in human immunodeficiency virus type 1-infected women.

The objective of the study was to measure antiretroviral exposures in four physiological compartments during pregnancy, delivery, and postpartum. This prospective, open-label, longitudinal study collected paired blood plasma (BP) and genital tract (GT) aspirates antepartum, at delivery, and up to 12 weeks postpartum. Antiretroviral cord BP and amniotic fluid concentrations were also measured. Drug concentrations were analyzed by validated high-performance liquid chromatography/UV and liquid chromatography/tandem mass spectrometry methods, with secondary compartment concentrations presented as the percentage of BP. Fourteen women taking lamivudine plus zidovudine and either lopinavir-ritonavir (n = 7), nelfinavir (n = 6), or nevirapine (n = 1) were enrolled; four also received tenofovir. GT penetration relative to BP was highest for the nucleoside reverse transcriptase inhibitors compared to the protease inhibitors and nevirapine. Only antepartum nelfinavir GT penetration was significantly higher than in the second trimester (geometric mean ratio [GMR], 179.3) or third trimester (GMR, 41.9). Compared to nonpregnant historical controls, antepartum GT penetration was significantly lower (P < 0.05) for zidovudine (GMR, 0.25) and lopinavir (GMR, 0.03); postpartum lopinavir GT penetration continued to be significantly lower (GMR, 0.27). Cord BP exposures were highest for lamivudine and tenofovir (> or = 100%), with cord BP levels of the remaining drugs ranging from 49 to 86% of that of the respective BP level. Amniotic exposures for lamivudine, zidovudine, tenofovir, and nelfinavir were > or = 100%, nevirapine exposure was 53%, and lopinavir and ritonavir exposures were < or = 6% that of BP. We conclude that GT, cord BP, and amniotic fluid exposures vary within and between antiretroviral drug classes and biologic sites. Measurement of antiretroviral exposure in maternal genital secretions, cord BP, and amniotic fluid may be needed to identify signals of subtherapeutic or supratherapeutic drug exposure.

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.

Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyceridemia.

BACKGROUND: Omega-3 fatty acids (fish oils) reduce fasting serum triglyceride levels and cardiovascular disease risk in individuals without HIV infection. Whether omega-3 fatty acid supplementation can reduce hypertriglyceridemia associated with antiretroviral therapy is not known. METHODS: We conducted an open-label, randomized trial that enrolled 52 patients receiving > or =3 active antiretrovirals who had fasting triglyceride levels of >200 mg/dL and were randomized to receive nutritionist-administered dietary and exercise counseling with or without fish oil supplementation for 16 weeks. RESULTS: Patients assigned to receive fish oil experienced a 25% mean decline in fasting triglyceride levels at week 4 (95% CI, -34.6% to -15.7% change), compared with a 2.8% mean increase among patients assigned to receive counseling alone (95% CI, -17.5% to +23.1% change) (P=.007). By week 16, the mean reduction in triglyceride levels in the fish oil arm remained significant, at 19.5% (95% CI, -34.9% to -4.0% change), whereas the mean decrease in the diet and exercise only arm was 5.7% (95% CI, -24.6% to +13.2% change); however, the difference between study arms was no longer statistically significant (P=.12). Low-density lipoprotein cholesterol levels had increased by 15.6% (95% CI, +4.8% to +26.4% change) at week 4 and by 22.4% (95% CI, +7.91% to +36.8% change) at week 16 in the fish oil arm but did not change in the diet and exercise only group. Fish oil was well tolerated; only 1 patient experienced treatment-limiting toxicity. Patients assigned to receive fish oil experienced a 25% mean decline in fasting triglyceride levels at week 4 (95% CI, -34.6% to -15.7% change), compared with a 2.8% mean increase in patients assigned to receive counseling alone (95% CI, -17.5% to 23.1% change) (P=.007). By week 16, the mean reduction in triglyceride levels in the fish oil arm remained significant, at 19.5% (95% CI, -34.9% to -4.0% change), whereas the mean decrease in the diet and exercise only arm was 5.7% (95% CI, -24.6% to 13.2% change); however, the difference between study arms was no longer statistically significant (P=.12). Low-density lipoprotein cholesterol levels had increased by 15.6% (95% CI, 4.8%-26.4% change) at week 4 and by 22.4% (95% CI, 7.91%-36.8% change) at week 16 in the fish oil arm but did not change in the diet and exercise only group. Fish oil was well tolerated; only 1 patient experienced treatment-limiting toxicity. CONCLUSIONS: Supplementation with omega-3 fatty acids in combination with dietary and exercise counseling was well tolerated and reduced fasting triglyceride levels in patients receiving antiretrovirals. To what extent the increase in low-density lipoprotein cholesterol levels observed in patients assigned this intervention is attributable to omega-3 fatty acid supplementation and whether this increase attenuates any benefit in lowering triglyceride levels is unclear. Given these results, further investigation of omega-3 fatty acid supplementation for the treatment of hypertriglyceridemia in HIV-infected patients is warranted.

Effect of release from prison and re-incarceration on the viral loads of HIV-infected individuals.

OBJECTIVES: The purpose of this study was to determine the effect of release from prison and subsequent re-incarceration on the viral loads of HIV-infected individuals receiving highly active antiretroviral therapy (HAART). METHODS: Fifteen re-incarcerated HIV-infected prisoners on HAART were identified from a retrospective cohort of HIV-infected prison inmates released from January 1, 1997, to August 31, 1999. The re-incarcerated prisoners were matched (1:2) to 30 HIV-infected incarcerated prisoners on HAART who remained incarcerated during the re-incarcerated participants' release time period. The outcomes measured were plasma HIV RNA levels, CD4+ lymphocyte counts, percentage of re-incarcerated and incarcerated participants with plasma HIV RNA levels <400 copies/mL, and the median change in plasma HIV RNA levels of the re-incarcerated and incarcerated participants at the end of the study. RESULTS: At the beginning of the study, 8/15 re-incarcerated participants had plasma HIV RNA levels <400 copies/mL, compared with 15/30 incarcerated participants. At the end of the study, only three of those eight re-incarcerated participants had plasma HIV RNA levels <400 copies/mL, compared with 14/15 incarcerated participants (p=0.0086). The median change in plasma HIV RNA levels of the re-incarcerated participants was 1.29 log10 copies/mL (interquartile range 0.04 to 1.70), compared with -0.03 log10 copies/mL (interquartile range -0.65 to 0.09) in the incarcerated participants (p=0.0183). CONCLUSIONS: Release from prison was associated with a deleterious effect on virological and immunological outcomes. These data suggest that comprehensive discharge planning efforts are required to make certain that HIV-infected inmates receive access to quality care following incarceration.

Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians.

AIM: Genetic polymorphisms have the potential to influence drug metabolism and vary among ethnic groups. This study evaluated the correlation of genetic polymorphisms with nevirapine pharmacokinetics exposure in Malawians. MATERIALS & METHODS: CYP450 2B6, 2D6, 3A4 and 3A5, ABCB1 and constitutive androstane receptor and pregnane X receptor, were analyzed for polymorphisms in 26 subjects. RESULTS: Allele frequencies (variant) were: CYP2B6 514G>T (0.31) CYP2D6*4 (0.02); CYP2D6*17 (0.35); CYP3A4*1B (0.77); CYP3A5*3 (0.25); ABCB1 2677G>T (0.0), ABCB1 3435C>T (0.21), NR1I3 13711152T>C (0.02), NR1I2 44477T>C (0.10), NR1I2 63396C>T (0.33), NR1I2 6-bp indel (del: 0.17). CYP2B6 516G>T (non-wild-type/wild-type) correlated with nevirapine pharmacokinetic parameters; geometric mean ratios (95% CI): 1.75 (1.27-2.40) for area under the concentration time curve (AUC)(0-12 h), 1.58 (1.03-2.42) for C(0), and 0.53 (0.31-0.91) for clearance. In a multivariable model, nevirapine AUC increased by 1.5% per year of age (p < 0.0001), CYP2B6 516 T allele increased AUC by 92% (p < 0.0001), and CYP3A5*3 decreased AUC by 31% (p = 0.0027). CONCLUSION: Allele frequencies were similar to other sub-Saharan African populations. The T allele for CYP2B6 516 was significantly associated with nevirapine exposure.

Plasma bile acid concentrations in patients with human immunodeficiency virus infection receiving protease inhibitor therapy: possible implications for hepatotoxicity.

STUDY OBJECTIVES: To evaluate whether patients with human immunodeficiency virus (HIV) infection who were receiving protease inhibitor therapy had altered bile acid concentrations compared with noninfected control subjects, and whether bile acid concentrations could predict the onset of hepatotoxicity caused by protease inhibitors. DESIGN: Retrospective sample analysis from a prospectively conducted clinical trial. SETTING: Academic research center. PATIENTS: Eleven adults with advanced HIV disease who were taking protease inhibitor-based antiretroviral therapy, one of whom had developed protease inhibitor-induced hepatotoxicity. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), and taurocholic acid (TC) were analyzed by using a novel high-performance liquid chromatography with tandem mass spectrometry detection method. Comparisons of the relative contribution of each bile acid to the total bile acid pool were made with previously published values and with bile acid concentrations contained in two pooled plasma samples from healthy, non-HIV-infected volunteers analyzed in our laboratory. Each pooled plasma sample used for this analysis contained contributions from three non-HIV-infected volunteers. The LCA and TC concentrations in HIV-infected patients were 3-4-fold higher than those previously reported for non-HIV-infected subjects; concentrations of other bile acids were similar to those of previous reports. The relative contribution of CDCA to the total bile acid pool was 9% in HIV-infected patients compared with 30-50% in noninfected subjects. Total and individual bile acid concentrations in the HIV-infected patient who developed hepatotoxicity were similar to the bile acid concentrations from the other study patients who did not develop hepatotoxicity. CONCLUSION: These data suggest that bile acid concentrations may be altered by HIV infection and/or protease inhibitor therapy. However, further investigations should be performed to assess whether antiretroviral-associated hepatotoxicity can be predicted by alterations in individual bile acid concentrations.

Effect of omeprazole on the plasma concentrations of indinavir when administered alone and in combination with ritonavir.

PURPOSE: The effects of omeprazole on indinavir when administered alone or in combination with ritonavir were evaluated. METHODS: Fourteen men and women age 18-55 years not infected with human immunodeficiency virus who met study qualifications were randomized to receive placebo, 20 mg of omeprazole, or 40 mg of omeprazole daily. After seven days, the single-dose pharmacokinetic profile of an 800-mg dose of indinavir alone or in combination with 200 mg of ritonavir was evaluated. Study participants received each of four study regimens in one of four randomly assigned orders. Blood samples were collected, and plasma indinavir and ritonavir concentrations were analyzed using high-performance liquid chromatography. RESULTS: The coadministration of 20 or 40 mg of omeprazole with indinavir significantly reduced the mean indinavir area under the concentration-versus-time curve (AUC) from 30.0 mg x hr/L (95% confidence interval [CI], 21.9-41.1 mg x hr/L) to 19.7 mg x hr/L (95% CI, 14.6-26.8 mg x hr/L) or 16.0 mg x hr/L (95% CI, 11.8-21.7 mg x hr/L), respectively (p < 0.002). The addition of 200 mg of ritonavir to 800 mg of indinavir in combination with 40 mg of omeprazole significantly increased the mean indinavir AUC from 30.0 mg x hr/L (95% CI, 21.9-41.1 mg x hr/L) to 46.6 mg x hr/L (95% CI, 34.0-63.8 mg x hr/L), but it did not significantly affect mean omeprazole concentrations (p < or = 0.02). CONCLUSION: The AUC of indinavir was substantially decreased in healthy volunteers who received omeprazole 20 or 40 mg daily for seven days before the administration of a single 800-mg dose of indinavir. Concomitant administration of ritonavir 200 mg with indinavir in participants receiving omeprazole led to a significant increase in the AUC of indinavir.

A 2-arm, randomized, controlled trial of a motivational interviewing-based intervention to improve adherence to antiretroviral therapy (ART) among patients failing or initiating ART.

RATIONALE AND PURPOSE: Motivational interviewing (MI) is a counseling technique that has been used effectively to change a number of health-related behaviors. We sought to assess the impact on patients' antiretroviral therapy (ART) adherence of a multicomponent, MI-based ART adherence intervention compared with that of an HIV informational control program. STUDY DESIGN: Two-arm, randomized, controlled trial. SAMPLE: One hundred forty adult HIV-infected patients attending a large, academic center infectious diseases clinic who were either failing or newly initiating an ART regimen. STUDY ENDPOINTS: (1) Mean adherence level (% of prescribed doses take in the prior month) at the week 12 visit, (2) change in mean adherence, (3) percentage of patients achieving >95% adherence in the third 4-week block, and (4) change in viral load. MAIN FINDINGS: The MI group's mean adherence improved by 4.5% compared with a decrease in the control group's adherence by 3.83% (P = 0.10). In the treatment group, 29% achieved >95% adherence compared with only 17% in the control group (P = 0.13). When we controlled for ethnicity, the intervention group had 2.75 times higher odds of achieving more than 95% adherence than did the controls (P = 0.045; 95% confidence interval: 1.023, 7.398). Although a number of mediating variables (beliefs about ART, coping style, social support, and goals set) had statistically significant changes in the expected direction in the MI group compared with controls, in the intent-to-treat analysis, the mean adherence at study exit for the intervention group was 76% (SD = 27%) and 71% (SD = 27%) for the control group (P = 0.62). CONCLUSION: Although not definitive, this study provides some evidence that MI offers an effective approach to improving adherence. Future studies able to build MI into the intervention for longer than 3 months may have a greater impact.

Dose separation does not overcome the pharmacokinetic interaction between fosamprenavir and lopinavir/ritonavir.

Previous investigations have shown a significant negative two-way drug interaction between fosamprenavir (FPV) and lopinavir/ritonavir (LPV/RTV) in both human immunodeficiency virus (HIV)-infected patients and seronegative volunteers. This randomized, nonblinded, three-way crossover study of HIV-seronegative adult volunteers investigated dose separation and increased doses of RTV as a means to overcome the interaction between FPV and LPV/RTV. Eleven HIV-seronegative volunteers were given FPV plus LPV/RTV at 700 mg plus 400/100 mg every 12 hours (q12h) simultaneously for 10 days and then randomized to receive each of three 7-day treatments in one of six possible sequences, as follows: FPV plus LPV/RTV at 700 mg plus 400 mg/100 mg q12h simultaneously, FPV/RTV at 700 mg/100 mg q12h plus LPV/RTV at 400 mg/100 mg q12h, with doses separated by 4 h, and FPV/RTV at 1,400 mg/200 mg in the morning plus LPV/RTV at 800 mg/200 mg in the evening. Pharmacokinetic sampling was performed on day 8 of each treatment, and samples were analyzed for FPV, amprenavir (APV), LPV, and RTV concentrations by high-performance liquid chromatography-tandem mass spectrometry. Geometric mean ratios (GMR [with 95% confidence intervals]) for the 4- and 12-h dose separation strategies compared to simultaneous administration were calculated for the areas under the concentration-time curves from 0 to 24 h. Compared to simultaneous administration, RTV exposures increased with both 4-h and 12-h dose separation strategies (GMR, 5.30 [3.66 to 7.67] and 4.45 [3.09 to 6.41], respectively). LPV exposures also significantly increased with both 4-h and 12-h dose separation strategies (GMR, 1.76 [1.34 to 2.32] and 1.43 [1.02 to 2.01], respectively). However, both the 4- and 12-h strategies resulted in greater reductions in APV exposure (0.67 [0.54 to 0.83] and 0.77 [0.59 to 0.99], respectively) compared to simultaneous administration. Additional investigations are warranted to determine the optimal dosing of FPV with LPV/RTV.

Brief but efficient: acute HIV infection and the sexual transmission of HIV.

BACKGROUND: We examined whether viral dynamics in the genital tract during the natural history of acute human immunodeficiency virus type 1 (HIV-1) infection could explain efficient heterosexual transmission of HIV. METHODS: We measured HIV-1 concentration in blood and semen samples from patients with acute and long-term HIV-1 infection. We explored the effect of changes in viral dynamics in semen on the probability of transmission per coital act, using a probabilistic model published elsewhere. RESULTS: Considered over time from infection, semen HIV-1 concentrations, in men with acute infection, increase and decrease in approximate parallel with changes occurring in blood. Modeling suggests that these acute dynamics alone are sufficient to increase probability of heterosexual transmission by 8-10-fold between peak (day 20 after infection, based on the model) and virologic set points (day 54 and later after infection). Depending on the frequency of coitus, men with average semen HIV-1 loads and without sexually transmitted diseases (STDs) would be expected to infect 7%-24% of susceptible female sex partners during the first 2 months of infection. The predicted infection rate would be much higher when either partner has an STD. CONCLUSIONS: Empirical biological data strongly support the hypothesis that sexual transmission by acutely infected individuals has a disproportionate effect on the spread of HIV-1 infection. Acute hyperinfectiousness may, in part, explain the current pandemic in heterosexual individuals.