Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection

BACKGROUND: Among HIV infected youth, the role of renal disease (RD) and its management has become more important as children/adolescents age into young adulthood. Identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications.” METHODS: Data collected from HIV-infected children and youth followed for ≥48 months was analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. RESULTS: 428 of 1874 at risk children (23%) developed RLE, which persisted in 229 of 428(54%). CD4<25% (hazard ratio[HR] 0.63, p<0.002) and HIV viral load>100,000 copies/ml (HR 0.31, p<0.01) were associated with reduced rates of resolution. Exposure to HAART/nephrotoxic HAART prior to or subsequent to RLE in most cases were not. Persistence of RLE was 88% sensitive for identifying new RD. Negative predictive values for RD were >95% for both the at risk cohort and in those with RLE. CONCLUSIONS: Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD

Psychosocial health problems increase risk for HIV among urban young men who have sex with men: Preliminary evidence of a syndemic in need of attention

BACKGROUND: Young men who have sex with men (YMSM) experience disparities in HIV rates and potentially in mental health, substance abuse, and exposure to violence.\ud \ud PURPOSE: We assessed the extent to which these psychosocial health problems had an additive effect on increasing HIV risk among YMSM.\ud \ud METHODS: An urban sample of 310 ethnically diverse YMSM reported on psychosocial health problems, sexual risk behaviors, and HIV status. A count of psychosocial health problems was calculated to test the additive relationship to HIV risk.\ud \ud RESULTS: The prevalence of psychosocial health problems varied from 23% for regular binge drinking to 34% for experiencing partner violence. Rates of sexual risk behaviors were high and 14% of YMSM reported receiving a HIV+ test result. Psychosocial health problems cooccurred, as evidenced by significant bivariate odds ratios (ORs) between 12 of the 15 associations tested. Number of psychosocial health problems significantly increased the odds of having multiple anal sex partners (OR=1.24), unprotected anal sex (OR=1.42), and an HIV-positive status (OR 1.42), after controlling for demographic factors.\ud \ud CONCLUSIONS: These data suggest the existence of cooccurring epidemics, or "syndemic," of health problems among YMSM. Disparities exist not only in the prevalence of HIV among YMSM but also in research to combat the epidemic within this vulnerable population. Future research is needed to identify risk and resiliency factors across the range of health disparities and develop interventions that address this syndemic.\ud \u

Pharmacokinetics of tenofovir during pregnancy and postpartum

Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum. Methods: International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24h post dose (AUC) was ≥1.99μg h/mL (nonpregnant historical control 10th percentile). Results: The median tenofovir AUC was decreased during the second (1.9μg h/mL) and third (2.4μg h/mL; P=0.005) trimesters versus postpartum (3.0μg h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P&gt;0.05). Median second/third-trimester troughs were lower (39/54ng/mL) than postpartum (61ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2kg, respectively; P=0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected. Conclusions: This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (&gt;90kg) or inadequate HIV RNA response