Patterns of a Rectal Microbicide Placebo Gel Use in a Preparatory Stage for a Phase I Trial Among Young Men Who Have Sex with Men.

We examined young gay, bisexual, and other men who have sex with men's (YGBMSM) usage patterns of a pre-coital, applicator-administered rectal placebo gel. An ethnically diverse sample of 94 YGBMSM (aged 18-30 years) were asked to insert hydroxyethylcellulose placebo gel rectally before receptive anal intercourse (RAI) and report their gel use through an interactive voice response system (IVRS) across 12 weeks. We used trajectory analyses to characterize participants' use of the rectal gel over the 12 weeks, and examine whether these trajectories varied based on participants' sociodemographic characteristics, sexual behaviors, application and insertion behaviors, and experiences using the placebo gel. A cubic model was the best fit for these longitudinal data, with two distinct trajectories of gel use observed. The first trajectory ('High with Varying Gel Use per Week') represented YGBMSM (N = 38; 40.3%) who reported using the rectal gel on several occasions per week. The second trajectory ('Low and Consistent Gel Use per Week') represented participants (N = 56; 59.7%) who reported a consistent average use of one gel per week. Participants in the High with Varying Gel Use Trajectory reported trying out a greater number of positions when inserting the gel across the 12-weeks than peers in the Low and Consistent Gel Use Trajectory. YGBMSM reporting more RAI occasions during the trial were more likely be present in the High with Varying Gel Use Trajectory than peers in the Low and Consistent Gel Use Trajectory. Future research examining how to facilitate gel application and adherence among YGBMSM is merited.

Prevalence and correlates of cervical HPV infection in a clinic-based sample of HIV-positive Hispanic women.

OBJECTIVES: Puerto Rico (PR), is the fifth highest jurisdiction of the United States of America (US) with respect to HIV prevalence and the leading in cervical cancer incidence. This cross-sectional study describes the prevalence and correlates of cervical HPV infection among a clinic-based sample of 302 women living with HIV/AIDS in PR. METHODS: Data collection included questionnaires, blood and cervical samples. Multivariable logistic regression models were used to estimate the magnitude of association (adjusted Prevalence odds ratio [aPOR]) between HPV cervical infection and other covariates. RESULTS: Mean age of participants was 40.3 years (± 10.3SD). The prevalence of HPV infection was 50.3%; 41.1% for low-risk types and 29.5% for high-risk types. Having ≥ 10 lifetime sexual partners (aPOR = 2.10, 95% CI:1.02-4.29), an abnormal Pap (aPOR = 3.58, 95% CI:1.93-6.62), active genital warts (aPOR = 3.45, 95% CI:1.60-7.42), and CD4 counts ≤ 200 (aPOR = 4.24, 95% CI: 1.67-10.78) were positively associated with any cervical HPV infection. Similar results were observed for HR HPV infection. CONCLUSIONS: A high burden of HPV co-infection exists among women living with HIV/AIDS in this population. Given the high incidence of HIV in PR and the higher risk of cervical cancer among women living with HIV/AIDS, HPV vaccination should be promoted in this population.

To Use a Rectal Microbicide, First Insert the Applicator: Gel and Applicator Satisfaction Among Young Men Who Have Sex With Men.

We examined how experiences with a rectal placebo gel and applicator used with receptive anal intercourse (RAI) related to young men who have sex with men's (YMSM) likelihood of using a rectal microbicide gel and applicator in the future. An ethnically diverse sample of 95 YMSM (aged 18 to 30 years) were asked to insert hydroxyethylcellulose (HEC) placebo gel rectally before RAI during 12 weeks and report the product's acceptability (i.e., satisfaction with applicator and gel, respectively; perceived gel side effects; and sexual satisfaction when gel was used) and likelihood of future microbicide use. Main and interaction effects predicting future use intentions were tested using linear regression. We found a positive association between future use intentions and applicator satisfaction (b = .33, p < .001). In a subsequent interaction effects model, we found that greater gel satisfaction was associated with increased future use intentions; however, the strength of this relationship was magnified when YMSM reported greatest satisfaction with the rectal applicator. Applicator satisfaction may be a salient factor in YMSM's decision-making to use a rectal microbicide in the future. Although the importance of developing a satisfactory rectal microbicide gel for YMSM is undeniable for its future use, our results also emphasize the importance of developing strategies that increase YMSM's comfort and skill when using a rectal applicator. Future research examining how to optimize the design, properties, and characteristics of a rectal applicator as a strategy to promote greater satisfaction and use among YMSM is merited.

[Environment and paediatric cancer in the Region of Murcia (Spain): integrating clinical and environmental history in a geographic information system]. / Medio ambiente y cáncer pediátrico en la Región de Murcia (España): integrando la historia clínica medioambiental en un sistema de información geográfica.

INTRODUCTION: Environment and Paediatric Cancer (PC) in the Region of Murcia (RM) is an on-going research project that has the following aims: to collect a careful paediatric environmental history (PEH) and to use geographical information systems (GIS) to map the incidence and analyze the geographic distribution of the PC incidence in the RM. The objectives are to present the methodology used for the collection and processing of data and disseminate initial results on the spatial and temporal incidence of PC in the RM (Spain). MATERIAL AND METHODS: A descriptive and georeference study of all PC cases under 15 years, diagnosed from 1 January 1998 to December 31, 2009. Three postal addresses were assigned to each case, residence during pregnancy, postnatal, and at the time of diagnosis. Other variables such as sex, date of birth, date of diagnosis, and histopathology classification were collected. RESULTS: No increase was observed in the trend of incidence of PC. The crude annual incidence rate was 14.3 cases per 100,000 children under 15 years. The standardised incidence ratio was higher in the north-west of the RM. Before diagnosis, 30% of cases had a different postal address than during the pregnancy. CONCLUSIONS: Integrating the spatial and temporal information through the PEH in a GIS should allow the identification and study of space-time clusters through an environmental monitoring system in order to know the importance of associated risk factors.

Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum.

OBJECTIVES: Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum. METHODS: The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC(0-12)) was >or=10th percentile NFV AUC(0-12) in non-pregnant historical controls (18.5 microg h/mL). RESULTS: Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (C(max)), 12-h post-dose concentration (C(12)) and AUC(0-12) were significantly lower during the third trimester compared to postpartum (P

Reduction in the perinatal HIV transmission: the experience at the Maternal Infant Studies Center and Gamma Projects at the University of Puerto Rico School of Medicine

The AIDS pandemic had a significant impact in Puerto Rico, especially among the heterosexual populations, in particular women. Women are one of the fastest growing risk groups with HIV/AIDS in the USA and constitute about half of the AIDS cases in the world. During the past 10 years Puerto Rico has ranked among the top 5 jurisdictions in the United States in AIDS cases rates, among men, women and children. In 1987 a universal prenatal HIV screening program was implemented in the University Hospital catchment area consisting of approximately 5,000 deliveries per year. Because of the early identification of pregnant women living with HIV, access to lifesaving clinical research and the implementation of multiple strategies and comprehensive care, the perinatal HIV transmission has been reduced to zero since 1997, with a blip of one case in 2002, and none since then. The availability and access to clinical and behavioral research has been one of the key elements for this success story. The programs involved and responsible for this spectacular outcome, namely the Maternal Infant Studies Center (CEMI-Spanish Acronym) and Gamma Projects at the University of Puerto Rico School of Medicine are described. The cost savings impact of stopping mother-infant perinatal HIV-1 transmission has been calculated to be approximately $34 to $58 million dollars in 10 years. The impact of the effectiveness of these programs in having healthy uninfected infants, prolonging and improving the quality of life of those living with HIV, and providing hope to families affected by this epidemic is incalculable.

Intracellular studies of the nucleoside reverse transcriptase inhibitor active metabolites: a review.

Nucleoside reverse transcriptase inhibitors (NRTIs) plasma concentrations do not correlate with clinical efficacy or toxicity. These agents need to be phosphorylated to become active against HIV-infection. Thus, the characterization of the NRTIs intracellular metabolite pharmacological parameters will provide a better understanding that could lead to the development of more rational dose regimens in the HIV-infected population. Furthermore, intracellular measurements of NRTIs may provide a better marker with respect to clinical efficacy and toxicity than plasma concentrations. Thus, in this article we review the latest information regarding the intracellular pharmacological parameters of zidovudine (ZDV) and lamivudine (3TC) active metabolites in HIV-infected patients including the results from our recent clinical studies. We will start the discussion with ZDV and 3TC clinical efficacy, followed by systemic pharmacokinetics studies. We will then discuss the in vitro and in vivo intracellular studies with particular emphasis in the method development to measure these metabolites and we will conclude with the most current data from our clinical trials.

CCR5 and beta-chemokines in HIV-1 infected children.

The duration from initial infection with HIV-1 to CD4 lymphocyte depletion and progression to AIDS varies among infected individuals. Despite treatment with highly active antiretroviral therapy (HAART), patients still show different stages of disease progression. We examined the role of beta-chemokines and its receptor, CCR5 in HIV-1 infected children in order to define determinants of HIV progression among treated individuals. Population was divided in two groups: Group 1--Long Term Non Progressors (LTNP) includes 10 patients with B1-B2 CDC disease classification and with a less aggressive therapy (only 2 in HAART); Group 2--Rapid Progressors (RP) includes 9 patients with C3 disease classification. All the patients had a CCR5 wild type (wt) genotype indicating that they do not have the 32 base-pair deletion associated with slower progression. There was an increased production of MIP 1-beta in 8/10 LTNP but only in 4/9 Progressors (Paired t-test/Wilcoxon Sign test, p-value < 0.05). The change in the levels of MIP-1 beta after PHA stimulation was statistically significant in both groups. The levels of RANTES increased in LTNP and RP and the change of the levels after mitogen stimulation was statistically significant for both groups included. The production of RANTES and MIP-1 beta in response to stimulation between both groups was not statistically significant. The production of MIP-1 alpha was variable in both groups and the difference in the levels after mitogen stimulation between the groups was not statistically significant. These results suggest that beta-chemokines do not play an important role in HIV-1 progression in children undergoing HAART.

Plasma glutathione concentrations in non-infected infants born from HIV-infected mothers: developmental profile.

Glutathione (GSH) is the primary antioxidant in humans. Oxidative cellular injury is postulated to be centrally involved in diverse processes including aging, cancer, cardiovascular disease, and Human Immunodeficiency Virus (HIV) disease progression. Normal plasma GSH concentrations have been well characterized in healthy children and adults, but not during infant development. The objectives of this study were to: a) measure plasma GSH concentrations in non-infected infants born from HIV-infected mothers, to b) assess the developmental variations with age and gender, and c) evaluate for possible associations with growth, anemia, and other maternal and infant variables. One hundred and seventy (170) plasma samples from 44 HIV-uninfected infants (birth to 18 mos.) born to HIV-infected mothers from the Women and Infant Transmission Study (Puerto Rico site) were analyzed. The total plasma GSH geometric mean concentration for all samples analyzed was 1.94 (1.06) mumoles/L. A developmental effect of age was seen with lower concentrations in younger infants (0-2 months) than in older infants 4-18 months. There was no significant effect of gender, anemia, zidovudine exposure, maternal age, maternal CD4 cell percent, or infant growth, although a trend towards increasing GSH concentration was seen with increasing weight for height z-score. These findings have multiple clinical ramifications including prediction of capacity to detoxify oxidants at different ages, and partial explanation for the increased viral loads seen in HIV-infected infants.

Plasma glutathione concentrations in children infected with human immunodeficiency virus.

BACKGROUND: Glutathione (GSH) is the principal intracellular defense against oxidants, and HIV-infected individuals tend to have subnormal concentrations in plasma. This GSH deficiency may contribute to the pathogenesis of disease progression. In the pediatric population correlations between GSH concentrations with clinical, immunologic and virologic disease profiles are scarce. OBJECTIVES: The main objectives of this study were (1) to compare plasma GSH concentrations of HIV-infected children and healthy controls and (2) to correlate GSH values with clinical, immunologic and virologic disease indices. METHODS: Twenty-four HIV-infected and 24 healthy control children entered the study. Plasma concentrations of total glutathione and related thiols were determined. RESULTS: The difference in mean plasma GSH concentrations between HIV-infected (2.96 +/- 0.31 microM) and control (6.62 +/- 0.58 microM) groups was highly significant (P < 0.0001). Linear regression analyses in HIV-infected patients revealed significant correlations between GSH and both absolute CD4+ cell counts (r = 0.56, P = 0.004) and viral load measured as log HIV-RNA PCR (r = -0.49, P = 0.018). GSH concentrations did not significantly correlate with CDC clinical stage but were lower in HIV-infected patients with growth failure (1.60 +/- 0.54 microM) vs. non-growth failure (3.23 +/- 0.33 microM); P = 0.05. CONCLUSIONS: This study confirmed that HIV-infected children are deficient in plasma GSH concentrations compared with healthy controls. We documented that low GSH concentrations in HIV-infected children are directly correlated with CD4+ cell counts and inversely correlated with viral loads. These findings support a possible role of GSH in the pathogenesis of HIV disease progression.