Zeitschrift für AIDS und klinische Forschung

Rifampicin reduces plasma concentration of most HIV protease inhibitors. Lopinavir boosted with ritonavir (LPV/r) could be an option to treat TB-HIV patients. Our aim was to evaluate lopinavir interaction with rifampicin during TB-HIV therapy. TB-HIV patients who could not use efavirenz and with no genotypic resistance to lopinavir were included. Rifampicin 600 mg, isoniazid 400 mg and pyrazinamide 2000 mg were started at day one for 6 months and LPV/r plus two nucleoside/nucleotide reverse transcriptase inhibitors were introduced at day 30. LPV/r dose was started at 400/100 mg BID and escalated over 7 days to 800/200 mg BID. Pharmacokinetic sampling was performed at day 15 (rifampicin), 45, 90, 180 (rifampicin, lopinavir, ritonavir) and 210 (lopinavir, ritonavir). Viral load (VL) and CD4 counts were performed at baseline and days 30, 60, 120, and 180. Genotypic testing was done in baseline and in the last visit. Fifteen patients were enrolled. Five were excluded during exclusively TB therapy. After LPV/r introduction five patients were excluded, three due to adverse events, and two due to low adherence. Five patients finished the study, two of them with VL<50 copies/mL. LPV/r genotypic resistance was detected in one patient. Lopinavir concentrations were below 1 μg/mL in 4/10 patients (in one study point), and one in two study points. Lopinavir concentrations were above 4 μg/mL in 6/10 patients, at least in one pharmacokinetic sample. Although target drug concentrations of lopinavir were achieved for most patients, adverse events were frequent and low adherence was observed for both TB and HIV therapies, showing how difficult it is to treat both diseases simultaneously. Hepatic and pancreatic enzymes should be routinely monitored.

Objective: Spanish-speaking individuals are disproportionately impacted by HIV in the United States. There are limited selections of valid and reliable measures to accurately assess the presence of HIV-associated neurocognitive disorders (HAND) with this population. The dearth of available measures places this vulnerable population at risk for receiving assessments that utilizes measures that are not adequately translated, modified, normed, or culturally sensitive. The purpose of this study was to investigate the clinical utility and efficacy of the Color Figure Mazes (CFM), a nonverbal measure of attention, concentration, working memory and executive functioning, to screen for deficits that characterize a HAND profile in Spanish-speaking adults. We hypothesized the HAND group would perform significantly worse than the non-HAND group and control group as the CFM tasks increased with difficul-ty. Methods: To explore the prevalence of HAND in Spanish-speaking individuals, we studied 100 HIV-1 seropositive participants (47 HAND; 53 non-HAND) who met criteria for the Center for Disease Control classification system category B or C and 27 HIV-seronegative controls. They were administered a comprehensive neuropsychological and psychosocial battery to assess for HAND. Results: While controlling for Pre-Morbid Intellectual Functioning, ANCOVA revealed that the HAND group performed significantly worse than the non-HAND group and HIV-seronegative control group on measures that placed a greater demand on skills requiring executive functioning including set-shifting over short periods of time, mental flexibility, and higher order thought processes. Conclusion: Our findings contribute to previous research by demonstrating that a brief, culturally sensitive measure, such as the CFM can help detect HAND in vulnerable populations, as is the case with Spanish speakers in the Unit-ed States. Furthermore, our results indicate that the CFM is sensitive in detecting executive function deficits associ-ated with HAND and may be culturally appropriate to use with HIV-seropositive Spanish-speaking adults.

Background: Antiretroviral therapy (ART) has greatly improved clinical outcomes in human immunodeciency virus (HIV) infection in adults and children. However, emerging data link ART to clinical lipodystrophy and premature atherosclerosis. We examined the impact of body fat changes on blood pressure and endothelial function in HIV infected children with and without ART. Methods: Central and peripheral body fat distribution was assessed in 68 HIV infected children. In all children blood pressure was measured and high resolution ultrasound was used to determine endothelium dependent dilatation (flow mediated dilatation-FMD) in the brachial artery. Results: From the 68 HIV infected children, 46 were on ART. There was no evidence of clinical lipodystrophy with ART in this cohort. Total cholesterol was increased in children on ART (p<0.001). FMD was significantly lower in those on ART compared to antiretroviral naive children (p<0.01). Increased BMI and waist as well as peripheral body circumference measurements in the arm and thigh were associated with higher systolic blood pressure (p<0.05 and p<0.01 respectively). An inverse association was noted between peripheral body composition measurements (zcalf and zthigh) and FMD (p<0.05 for both). Conclusion: HIV-infected children on ART have deranged lipids and evidence of early arterial abnormalities. Increased body fat accumulation is associated with reduced endothelial function and elevated blood pressure in HIVinfected children. These findings suggest that healthy dietary intake and weight control would be advisable in HIV infected children for optimal vascular disease prevention.

Objectives: Self-administered vaginal rings are a promising method for delivery of topical anti-HIV microbicides and might offer an adherence advantage over daily or coitally-dependent dosage forms such as gels. This trial assessed the safety and pharmacokinetic aspects of the Dapivirine Vaginal Ring-004 when worn as multiple rings over sequential periods of ring use by healthy, sexually-active, HIV-negative women. Methods: This double-blind trial was conducted among 48 women (18-40 years). Participants were randomly assigned to two groups (A or B) and received (3:1) either the dapivirine or a placebo vaginal ring. Group A used two rings over a 56-day period and Group B used three rings over a 57-day period. Safety evaluations were conducted throughout the trial. Dapivirine concentrations were measured in plasma, vaginal fluid and cervical tissue samples collected during and after the 56 days (Group A) or 57 days (Group B) of vaginal ring use. Results: Ring-004 was safe and well tolerated in all participants. The pharmacokinetic profile demonstrated a rapid increase in plasma and vaginal fluid concentrations and achieved concentrations in vaginal fluids and cervical tissue well above the in vitro IC99 in cervical tissue (3.3 ng/mL) that were sustained for a 28 to 35-day ring use period (approximately 3000 times higher in vaginal fluids and 14 -1000 times higher in cervical tissue). Drug levels were associated with significant inhibitory activity of genital secretions against HIV ex vivo, a biomarker of pharmacodynamics. Individual plasma dapivirine concentrations did not exceed 553 pg/mL and were well below plasma concentrations at the maximum tolerated dose for oral treatment (mean Cmax 2286 ng/mL). Conclusions: The consecutive use of several rings over a period of up to 57 days was safe and well tolerated, and PK data indicate that a single Ring-004 is likely to be protective for at least 35 days.

Objectives: A secondary analysis of clinical trial data was used to: (1) estimate retention one year after antiretroviral therapy (ART) initiation; (2) determine factors associated with attrition; and (3) investigate whether participants deemed lost to follow-up (LTFU) were still engaged with the clinic through an interactive mobile phone intervention. Methods: Between 2007 and 2008, adults initiating ART were recruited from three clinics in Kenya. Telephone and community tracing were undertaken to track participants who did not attend their 12-month appointment. Logistic regression was used to determine the association between an interactive text-messaging intervention, purposively selected clinical and socio-demographic factors, and attrition. Data on participant engagement with the text-messaging intervention were extracted from a communications log. Results: Data from 538 participants were included. Retention in care at 6-months was 86.2% (461/535), decreasing to 81.8% (431/527) at 12-months. At 12-months, 53% (51/96) of attrition was due to death and 47% (45/96) to LTFU. A baseline CD4 count <100 was significantly associated with greater attrition (adjusted odds ratio [AOR]=1.83, 95%CI: 1.14-2.94). At 12-months, increased travel time to clinic was significantly associated with greater attrition in females (AOR 1.55, 95%CI: 1.12-2.14), but not in males (AOR 0.95, 95%CI: 0.65-1.39). Of 16 intervention arm participants considered LTFU at 6-months, 11 were in contact with the clinic through text-messaging. At 12-months, less than half (7/18) of participants considered LTFU who were enrolled in the service were participating in the intervention. Conclusions: Our results confirm the association between a low baseline CD4 count and attrition, and suggest that travel time to the clinic is an important factor in retaining female patients. They highlight the importance of tracing studies to estimate retention and the opportunity provided by an interactive mobile health intervention to connect with patients considered LTFU.

Objective: There continues to be a large disparity in the prevalence of HIV/AIDS among men who have sex with men (MSM) compared to all other populations. Recent research suggests discriminatory laws may play a role in the health outcomes of the LGBT community. We hypothesized that discriminatory state-level relationship recognition, employment, and housing policies would predict a higher proportion of MSM among the population living with AIDS than heterosexuals while controlling for state-level healthcare quality and political orientation. Method: Data for the proportion of AIDS cases comprised of MSM and heterosexuals were collected for 2008 for each state from CDC 2010 State Surveillance Reports. Additionally, relationship recognition, housing discrimination, and employment discrimination laws were collected from 2008 for each state. Covariates included the political orientation of each state based on the 2008 presidential election and a composite measure of overall healthcare quality of each state created by the Agency for Healthcare Research and Quality. Results: Overall, MSM account for the highest proportion of people living with AIDS in the US. Hierarchical regressions indicated that MSM accounted for a higher proportion of people living with AIDS in states with discriminatory relationship recognition policies. Housing discrimination policies, employment discrimination policies, healthcare quality, and political orientation were not associated with the proportion of MSM or heterosexuals that comprise the total population of people living with AIDS in each state. Conclusion: Findings suggest relationship recognitions are a unique protective factor against HIV/AIDS for MSM. Future research is needed to fully understand the mechanisms by which relationship recognitions serve as a protective factor from HIV/AIDS for MSM.

The authors present a case of sporotrichosis, a systemic fungal infection frequently observed in Rio de Janeiro, where nowadays most cases are transmitted by cats. The disseminated cutaneous form, as seen in our patient, is rare and shows multiple cutaneous lesions. This form is almost always associated with immunosuppression, as the case we present, who was diagnosed as HIV+ during the diagnostic evaluation of the mycosis.