HIV Prevalence,Risk Behavior,Hormone Use and Surgical History Among Transgender Persons in Thailand

While Male-to-female transgender persons (TG) are believed to often engage in sex work and have high HIV infection risk, little is known about demographics, surgical and hormone use history, risk behaviors and HIV prevalence. Between March and October 2005, 474 TG from Bangkok, Chiangmai, and Phuket were surveyed using venue-day-time sampling. Of 474 participants, overall HIV prevalence was 13.5%. Most participants had completed at least secondary or vocational education (79.2%), gender self-identified as female (89.0%), had received money, gifts or valuables for sex (60.8%), and reported hormone use (88.6%). Surgical history was taken from 325 participants. Of these, 68.6% reported some form of surgery and 11.1% had undergone penile-vaginal reconstructive surgery. In multivariate analysis, being recruited from a park/street; older age, anal sex role identification as “versatile” and anal sex debut before age 13 were independently associated with HIV prevalence. The development, implementation and evaluation of culturally appropriate sexual health interventions for Thai TG is urgently needed.     

Pharmacokinetics of Stavudine and Didanosine Coadministered with Nelfinavir in Human Immunodeficiency Virus-Exposed Neonates

We evaluated the pharmacokinetics of stavudine (d4T) and didanosine (ddI) in neonates. Eight neonates born to human immunodeficiency virus-infected mothers were enrolled to receive 1 mg of d4T per kg of body weight twice daily and 100 mg of ddI per m(2) once daily in combination with nelfinavir for 4 weeks after birth. Pharmacokinetic evaluations were performed at 14 and 28 days of age. For d4T, on days 14 and 28, the median areas under the concentration-time curves from 0 to 12 h (AUC(0-12)s) were 1,866 and 1,603, ng x h/ml, respectively, and the median peak concentrations (C(max)s) were 463 and 507 ng/ml, respectively. For ddI, on days 14 and 28, the median AUC(0-10)s were 1,573 and 1,562 h x ng/ml, respectively, and the median C(max)s were 627 and 687 ng/ml, respectively. Systemic levels of exposure to d4T were comparable to those seen in children, suggesting that the pediatric dose of 1 mg/kg twice daily is appropriate for neonates at 2 to 4 weeks of age. Levels of exposure to ddI were modestly higher than those seen in children. Whether this observation warrants a reduction of the ddI dose in neonates is unclear.     

One-year experience of nucleic acid technology testing for human immunodeficiency virus Type 1, hepatitis C virus, and hepatitis B virus in Thai blood donations

BACKGROUND: Blood donations collected at the National Blood Center, the Thai Red Cross Society, Bangkok, in 2007 were tested by nucleic acid amplification technology (NAT) using the Chiron TIGRIS/Procleix Ultrio test and the Roche cobas s 201/cobas TaqScreen multiplex (MPX) test.
STUDY DESIGN AND METHODS: The sensitivity, specificity, and robustness were determined by testing 486,676 seronegative blood donations. Samples from each day of collection were divided into two sets; the odd-numbered samples were tested individually on the TIGRIS and the even-numbered samples were tested in pools of 6 on the cobas s 201. The status of reactive samples was confirmed by duplicate testing of samples from the plasma bag to calculate the test specificity. Reactive samples were tested on the alternate system and followed up.
RESULTS: The analytical sensitivity of both systems met the 95% limits of detection claimed by the respective package inserts. No cross contamination was seen with either system. Test specificity was 99.93 and 99.90% for the Procleix Ultrio and cobas TaqScreen tests, respectively. The NAT yield rates for human immunodeficiency virus Type 1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) were 1:97,000, 1:490,000, and 1:2800, respectively. Several occult HBV donors, the majority of whom were detected by both tests, were also identified. The HIV-1 and HCV window cases were detected with both tests.
CONCLUSION: The performances of the systems and tests indicated that both were acceptable for routine NAT by the National Blood Center, the Thai Red Cross Society. However, the Procleix Ultrio test appeared to be less sensitive than the cobas TaqScreen test for HBV.     

Effects of highly active antiretroviral therapy (HAART) on psychomotor performance in children with HIV disease

OBJECTIVE: This study assesses the effects of HAART on psychomotor performance of symptomatic HIV-infected children. It is one of the first studies to look at neurobehavioral functioning in children infected with HIV in resource-limited countries. DESIGN: A longitudinal pilot study of vertically HIV-infected children at the HIV Netherlands Australia Thailand Research Collaboration Center in Bangkok, Thailand. METHODS: A total of 34 children participated in the study of whom 16 had never received antiretroviral (ARV) therapy and were about to start HAART (Newly treated children), 7 did not receive antiretroviral therapy (Untreated children) and 11 had been treated with HAART for more than one year (HAART experienced children). All children were administered 4 psychomotor tasks at baseline and after 4 months. The Newly treated and the Untreated children were also evaluated after 12 months. RESULTS: In general, the children performed similarly on all psychomotor tasks at baseline. After 12 months of HAART, there was a significant increase in CD4% in the Newly treated group. Overall, psychomotor performance did not change at the 4-month evaluation in all groups. At the 12-month evaluation psychomotor performance had deteriorated substantially on all tasks in both the Newly treated and the Untreated children. CONCLUSIONS: There was no significant difference in psychomotor functioning between children newly treated, previously treated and untreated with HAART over the course of one year. Psychomotor performance deteriorated after 12 months of HAART, which provides important indications concerning the lack of benefits of HAART on psychomotor functions in children despite immunologic reconstitution. Further research with larger sample sizes is needed to confirm these findings.     

Dose-escalating study of the safety and pharmacokinetics of nelfinavir in HIV-exposed neonates

The pharmacokinetics of nelfinavir (NFV) in neonates younger than 4 weeks of age was assessed. Three cohorts of HIV-exposed neonates were enrolled in cohorts to receive 15, 30, and 45 mg of NFV/kg twice daily in combination with stavudine and didanosine for 4 weeks after birth. Trough NFV concentrations (C(min)) were measured at 1 and 7 days of age. Intensive pharmacokinetic evaluations were performed at 14 and 28 days of age. The median NFV C(min) values in the 15 mg/kg (6 patients), 30 mg/kg (5), and 45 mg/kg (11) cohorts at 1, 7, 14, and 28 days of age were 0.19, 1.21, 0.51, and 0.33; 1.02, 3.18, 0.73, and 0.55; and 0.67, 3.21, 0.70, and 0.73 mg/L, respectively. The median area under the plasma concentration-versus-time curve values over 12 hours in the three cohorts at 14 and 28 days of age were 14.4 and 8.7, 19.4 and 15.8, and 23.4 and 18.5 (h. mg)/L, respectively. No serious adverse events were observed. In conclusion, the systemic exposure of NFV decreased after 7 days of age, possibly because of hepatic enzyme maturation, autoinduction of NFV metabolism, and/or changes in NFV absorption. The highly variable systemic exposure observed in the study indicates that therapeutic drug monitoring seems warranted to ensure adequate NFV dosing in this population.     

Interindividual variability of once-daily ritonavir boosted saquinavir pharmacokinetics in Thai and UK patients

OBJECTIVES: Differential exposure to saquinavir/ritonavir may lead to therapy failure. The objective was to identify factors that influence variability of saquinavir/ritonavir plasma concentrations. METHODS: Saquinavir/ritonavir data, dosed as 1600/100 mg once daily, from three separate pharmacokinetic studies, in 45 patients from Thailand and the UK, were pooled. Pharmacokinetic parameters were based on non-compartmental analysis. Univariate analysis was performed with saquinavir as the dependent variable, and ritonavir area under the curve (AUC), gender, body weight, body mass index (BMI) and study site as independent variables. Variables with a P value <0.10 were included in a multivariate linear regression analysis. RESULTS: Higher saquinavir AUCs, maximum concentrations (Cmax) and minimum concentrations (Cmin) were seen in Thai patients than in UK patients. Univariate analysis showed associations between body weight, gender, study site and ritonavir AUC and saquinavir AUC (P < 0.05), whereas BMI (P = 0.13) did not. In the multivariate analysis, ritonavir AUC (P = 0.0001) and study site (P = 0.0021) were significantly related to saquinavir AUC (R2 = 0.50). CONCLUSIONS: The ritonavir AUC and study site appeared to be related to exposure of saquinavir. Study site should be viewed as the total of country- and study-specific differences--such as differences in lifestyle, environment, genetic background and dietary composition--between the analysed studies.     

Construction and immunogenicity study of a 297-bp humanized HIV V3 DNA of an approximated last common ancestor in mice

DNA immunization represents one of the promising HIV-1 vaccine approaches. To overcome the obstacle of genetic variation, we used the last common ancestor (LCA) or "center-of-the-tree" approach to study a DNA fragment of the HIV-1 envelope surrounding the V3 region. A humanized codon of the 297-bp consensus ancestral sequence of the HIV-1 envelope (codons 291-391) was derived from the 80 most recent HIV-1 isolates from the 8 circulating HIV-1 subtypes worldwide. This 297-bp humanized "multi-clade" V3 DNA was amplified by a PCR-based technique. The PCR product was well expressed in vitro whereas the corresponding non-humanized V3 DNA (subtype A/E) could not be expressed. However, both V3 DNA constructs as well as the full-length HIV-1 envelope construct (A/E) were found to be immunogenic in mice by the footpad-swelling assay. Moreover, intracellular and extracellular interferon-gamma could be detected upon in vitro stimulation of spleen cells although the response was relatively weak. Further improvement of our humanized V3 DNA is needed.