Population pharmacokinetics of ravidasvir in adults with chronic hepatitis C virus infection and impact of antiretroviral treatment.

Ravidasvir (RDV) is a novel NS5A inhibitor that exhibits potent pan-genotypic inhibition of hepatitis C virus (HCV) replication. Sofosbuvir (SOF) plus RDV was demonstrated to be efficacious and safe in adults with active HCV infection, including those living with HIV (LWHIV), in the STORM-C-1 trial. We assessed the population pharmacokinetics (PK) of RDV in a sub-study nested within STORM-C-1 conducted in Thailand and Malaysia. SOF (400 mg) plus RDV (200 mg) was administered orally once daily for 12 weeks to adults with chronic HCV infection, but without cirrhosis and for 24 weeks to those with compensated cirrhosis. Intensive and sparse PK samples were collected at 4, 8, and 12 weeks after treatment initiation. Population PK parameters of RDV and the impact of covariates were evaluated using nonlinear mixed-effects modeling. Five hundred ninety-four participants were included, 235 (40%) had compensated cirrhosis, and 189 (32%) were LWHIV. RDV plasma concentrations were best described by a two-compartment model with first-order elimination. Oral clearance (CL/F) and volume of distribution (Vd/F) parameters were allometrically scaled on fat-free mass. Concomitant antiretroviral treatment (ART) increased RDV CL/F by 30%-60%, with efavirenz-based ART having the largest impact. Females had 16% lower RDV CL/F than males, and higher albumin levels reduced RDV central volume of distribution. While several covariates impact RDV CL/F and Vd/F, the effect on RDV exposures was not clinically relevant based on the efficacy data reported in this diverse Asian adult population. There were no meaningful drug-drug interactions in adults LWHIV on ART.

Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

BACKGROUND: Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin. METHODS: In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group). RESULTS: From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in the placebo group (P=0.29). CONCLUSIONS: In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822 .).

Monitoring HIV Drug Resistance: Early Warning Indicators to Assess Performance of Thailand's Antiretroviral Treatment Program.

OBJECTIVE: To describe trends in Thailand's antiretroviral treatment (ART) program performance assessed by HIV drug resistance early warning indicators (EWIs), as recommended by WHO, between 2009 and 2013. MATERIAL AND METHOD: Seven EWIs were monitored, viral load (VL) testing coverage, VL suppression, retention in ART, lost to follow-up (LTFU), antiretrovirals (ARVs) dispensing practices, on-time pill pick-up, and pharmacy stock-outs. Data from ART adult patients in National Health Security Office Scheme were analyzed except for pharmacy stock-outs, which were reported from hospitals. Aggregated averages were calculated for each EWI. Chi-square for trend was applied to measure significant changes. RESULTS: By September 2013, 174,284 adults were receiving ART at 929 hospitals. Over time, improvement in VL testing coverage (53.8% in 2009 to 79.8% in 2013) was observed. VL suppression and on-time pill pick up rates were well above 90%. Rates of retention in ART declined from 84.0 to 82.9%, whereas LTFU rates increased from 8.3 to 9.2% (p<0.001). Prescriptions with inappropriate ARVs decreased from 0.32 to 0.10% (p<0.001). Of reporting hospitals, 96.1%, 96.3%, and 96.2% observed no ARVs stock-out between 2011 and 2013. CONCLUSION: EWI is a useful tool to monitor ART program performance and to identify area where improvement is needed.

Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

BACKGROUND: Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand. METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3)) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm(3). The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6-11.4) in VL versus 7.4% (5.1-10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2-8.4) in VL versus 7.5% (5.0-11.1) in CD4 (p=0.097). Median time from treatment initiation to switch was 11.7 months (7.7-19.4) in VL and 24.7 months (15.9-35.0) in CD4 (p=0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p=0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported. CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary.

HIVQUAL-T: monitoring and improving HIV clinical care in Thailand, 2002-08.

OBJECTIVE: We report experience of HIVQUAL-T implementation in Thailand. DESIGN: Program evaluation. SETTING: Twelve government hospital clinics. PARTICIPANTS: People living with HIV/AIDS (PLHAs) aged ≥15 years with two or more visits to the hospitals during 2002-08. INTERVENTION: HIVQUAL-T is a process for HIV care performance measurement (PM) and quality improvement (QI). The program includes PM using a sample of eligible cases and establishment of a locally led QI infrastructure and process. PM indicators are based on Thai national HIV care guidelines. QI projects address needs identified through PM; regional workshops facilitate peer learning. Annual benchmarking with repeat measurement is used to monitor progress. MAIN OUTCOME MEASURE: Percentages of eligible cases receiving various HIV services. RESULTS: Across 12 participating hospitals, HIV care caseloads were 4855 in 2002 and 13 887 in 2008. On average, 10-15% of cases were included in the PM sample. Percentages of eligible cases receiving CD4 testing in 2002 and 2008, respectively, were 24 and 99% (P< 0.001); for ARV treatment, 100 and 90% (P= 0.74); for Pneumocystis jiroveci pneumonia prophylaxis, 94 and 93% (P= 0.95); for Papanicolau smear, 0 and 67% (P< 0.001); for syphilis screening, 0 and 94% (P< 0.001); and for tuberculosis screening, 24 and 99% (P< 0.01). PM results contributed to local QI projects and national policy changes. CONCLUSIONS: Hospitals participating in HIVQUAL-T significantly increased their performance in several fundamental areas of HIV care linked to health outcomes for PLHA. This model of PM-QI has improved clinical care and implementation of HIV guidelines in hospital-based clinics in Thailand.

High Proportion of Blood-Borne and Sexually Transmitted Infections Among People Deprived of Liberty in a Central Male Prison in Thailand: A Cross-Sectional Study 2018-2019.

Data are lacking or outdated on burden of HIV, viral hepatitis infection, and sexually transmitted infections such as syphilis among people deprived of liberty in the Asia-Pacific region. We aimed to evaluate the proportion of viral hepatitis B (HBV), hepatitis C (HCV), HIV, and syphilis infections, and factors associated with HCV, HBV, and HIV infection in a central male prison. A cross-sectional study was performed among 1,028 people deprived of liberty from a central male prison in Bangkok, Thailand. People deprived of liberty were screened for HIV, HBV, HCV, and syphilis infections during 2018-2019. HBV and HCV were defined as positive hepatitis B surface antigen and positive anti-HCV antibody, respectively. Proportions (95% confidence interval [CI]) of infections were calculated based on the binomial distribution. HBV proportion was reported for different age groups. Risk factors associated with HCV infections were evaluated by logistic regression model. The median age was 38 (interquartile range, 32-50) years, and 6.9% reported use of injection drugs. The proportion of HIV, HBV, anti-HCV, HCV RNA, and syphilis was 2.9% (95% CI, 1.9-4.1), 6.4% (5-8.1), 5.9% (4.6-7.6), 4.2% (3-5.6), and 4.8% (3.5-6.3), respectively. One (0.1%), 7 (0.6%), and 2 (3%) were co-infected with HIV/HBV, HIV/HCV, and HDV/HBV, respectively. HBV proportion differed across age groups: 3.7% in <30 years, 7% in 31-40 years, 9.7% in 41-50 years, and 5.5% in >50 years. Factors associated with HCV infection were older age, lower education level, previous incarceration, and injection drug use. In multivariable models, older age was associated with HBV infection, and men having sex with men was associated with HIV infection. The proportion of blood-borne infections was higher among males than among the general population. HBV vaccination, routine HCV screening, and treatment with pan-genotypic direct-acting antivirals with minimal specialist requirements should be implemented in Thai prisons.

Brief Report: HCV Universal Test-and-Treat With Direct Acting Antivirals for Prisoners With or Without HIV: A Prison Health Care Workers-Led Model for HCV Microelimination in Thailand.

BACKGROUND: This study investigated the sustained virologic responses (SVRs) among prisoners with hepatitis C virus (HCV) using universal test-and-treat approach by prison health care workers in a central male prison in Thailand. METHODS: A universal HCV screening was conducted in a maximum-security central prison (Klong Prem Central Prison) in Thailand. HCV RNA-confirmed prisoners were treated with generic sofosbuvir/velpatasvir by prison health care workers, regardless of their HCV genotypes and duration of prison sentences. We evaluated the SVR rates at 12 weeks after completing direct acting antivirals (DAA) treatment. RESULTS: A total of 68 prisoners with detectable HCV RNA received DAA treatment. The median age and duration of prison sentences were 44 years (interquartile range, 41-53) and 25 (interquartile range, 19-33) years, respectively. Twenty-five percentage of the participants was coinfected with HIV, and 6% of the participants was coinfected with hepatitis B virus. Among all prisoners who received DAA treatment, 20 (29%) had genotype (GT)-1a, 3 (4%) had GT-1b, 22 (32%) had GT-3a, 3 (4%) had GT-3b, and 7 (10%) had GT-6. Overall, improvements in liver biomarkers were seen after HCV treatment, and SVR was achieved in 97% of the participants with per-protocol analysis and in 90% of the participants with intention-to-treat analysis. CONCLUSIONS: HCV treatment using DAA among prisoners through universal test-and-treat approach led by prison health care workers is highly effective and safe, and such model can potentially help to facilitate the goals of HCV microelimination among prisoners in Thailand.

Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial.

BACKGROUND: In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV. METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183. FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment. INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality. FUNDING: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

HIV Drug Resistance among Pre-treatment Cases in Thailand: Four Rounds of Surveys during 2006-2013.

In Thailand, antiretroviral therapy (ART) was initiated to treat human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) cases using the empirical regimen with no prior genotypic test to determine drug resistance. In order to assess prevalence rate of HIV drug resistance (HIVDR) among pre-treatment cases, four rounds of survey were carried out in ART clinics, including six, eight, 33 and four ART clinics in each round during 2006-2013. For which, HIVDR testing results were available in 310, 350, 797, and 413 cases in four rounds. It was revealed that HIVDR rates among naive cases were 2.0%, 2.8%, 4.0% and 4.8%, while in experienced cases, the rates were 0, 3.3%, 11.4% and 13.9%. The rates among all cases were 1.9%, 2.9%, 4.4% and 5.6%. Resistant drugs with the highest rates among all cases in the survey round 4 were nevirapine (3.6%) and efavirenz (3.1%). The results indicated the need to continue surveillance for pre-treatment HIVDR, and posed challenges to implement activities for protecting efficacy and prolong the use of empirical first-line regimen. A strategy to apply genotyping test, in a cost-effective approach, should be considered to prepare for situation when HIVDR increases beyond a critical level.

Loss to follow-up and associated factors of patients in the National AIDS Program in Thailand.

BACKGROUND: Loss to follow-up (LTFU) is a crucial indicator to evaluate the effectiveness of HIV care and treatment programmes. We assessed the LTFU rate and associated factors of Thai HIV-infected patients who enrolled in the National AIDS Program (NAP) for two periods: prior to (pre-ART) and after starting ART (ART-patients). METHODS: Thai HIV patients aged ≥15 years enrolled in NAP from 2008 to 2014. Vital status was ascertained by linkage with the National Death Registry. Competing risk models were used to calculate the adjusted sub-distribution hazards (aSHR) for LTFU for pre-ART and ART-patients, with death considered as a competing risk. RESULTS: A total of 157,026 patients registered in care and were included in analyses. The cumulative incidence of LTFU in pre-ART patients at 1 year was 10.2%, whereas in ART-patients it was 12.8%. Among pre-ART patients, younger age (<30 versus ≥45 years, aSHR 1.60, 95% CI 1.49, 1.72), less advanced HIV stage (aSHR 1.29, 95% CI 1.21, 1.37) and higher CD4+ T-cell count (≥350 versus <100, aSHR 6.31, 95% CI 5.74, 6.95) had a higher chance of LTFU. ART-patients with high baseline CD4+ T-cell count (CD4 ≥350 versus CD4 <50, aSHR 2.06, 95% CI 1.97, 2.15) and non-advanced HIV stage had increased risk of LTFU. CONCLUSIONS: Our findings provide new evidence of the LTFU rate in Thai HIV-infected patients in NAP. Emphasis needs to be placed on improving follow-up in all patients with higher CD4+ T-cell counts. LTFU will be important to monitor as programmes move to commence ART regardless of CD4+ T-cell count.

The economics of effective AIDS treatment in Thailand.

INTRODUCTION: The speed with which Thailand has scaled up public provision of antiretroviral therapy (ART) has been unprecedented, with more than 80 000 individuals on treatment at the end of 2006 through Thailand's National Access to Antiretroviral Program for People Living with HIV/AIDS (NAPHA). This paper projects the cost effectiveness, the affordability and the future fiscal burden of NAPHA to the government of Thailand under several different policy scenarios until the year 2025. METHODS: An economic/epidemiological model of access to ART was constructed, and this composite model was calibrated to economic and epidemiological data from Thailand and other countries. The economic model adopts the conditional logit specification of demand allocation across multiple treatment modes, and the epidemiological model is a deterministic difference-equation model fitted to the cumulated data on HIV incidence in each risk group. RESULTS: The paper estimates that under 2005 prices NAPHA will save life-years at approximately US$736 per life-year saved with first-line drugs alone and for approximately US$2145 per life-year if second-line drugs are included. Enhancing NAPHA with policies to recruit patients soon after they are first eligible for ART or to enhance their adherence would raise the cost per life-year saved, but the cost would be small per additional life-year saved, and is therefore justifiable. The fiscal burden of a policy including second as well as first-line drugs would be substantial, rising to 23% of the total health budget by 2014, but the authors judge this cost to be affordable given Thailand's strong overall economic performance. The paper estimates that a 90% reduction in the future cost of second-line therapy by the exercise of Thailand's World Trade Organization authority to issue compulsory licences would save the government approximately US$3.2 billion to 2025 and reduce the cost of NAPHA per life-year saved from US$2145 to approximately US$940.

Acceptability of Carraguard vaginal gel use among Thai couples.

OBJECTIVES: To evaluate the acceptability of candidate microbicide Carraguard among couples participating in a safety trial. STUDY DESIGN: A 6-month randomized, placebo-controlled trial was conducted in sexually active, low-risk couples in Thailand. METHODS: Couples who were monogamous, HIV uninfected, and not regular condom users were enrolled. Acceptability data were collected through structured questionnaires at repeated intervals. At the closing study visit, participants were asked questions about hypothetical product characteristics and future use. Compliance with gel use was assessed by questionnaires, coital diaries, and tracking of used and unused applicators. RESULTS: Among 55 enrolled couples, follow up and adherence with gel use were high and sustained, with 80% of women using gel in over 95% of vaginal sex acts. Because acceptability results from Carraguard and placebo arms were similar, they were combined for this analysis. Overall, 92% of women and 83% of men liked the gel somewhat or very much; 66% of women and 72% of men reported increased sexual pleasure with gel use; and 55% of women and 62% of men reported increased frequency of intercourse. Only 15% of women but 43% of men thought that gel could be used without the man knowing. Although men and women had similar views overall, concordance within couples was low, with no kappa coefficients above 0.31. CONCLUSION: Carraguard gel use was acceptable to low-risk couples in northern Thailand. Reported associations between gel use and increased sexual pleasure and frequency suggest a potential to market microbicide products for both disease prevention and enhancement of pleasure.

The National Access to Antiretroviral Program for PHA (NAPHA) in Thailand.

To describe the development, components, initial results and lessons learned from Thailand's National Access to Antiretroviral Program for People living with HIV/AIDS (NAPHA), a historical review was conducted and program monitoring was analyzed. The national antiretroviral therapy program at different levels of the public health system was implemented with all major program components; ARV protocol development, health care professional training, drug supply chain management, laboratory network formation, monitoring and evaluation, and multi-sector and PHA involvement since 2001, which was based on elements of research, pilot projects, training, national guideline development, experiences and policy making. A national monitoring system was developed to monitor the progress of the program. From February 2001 to December 2004, the monitoring reports received from implementing hospitals showed that 58,133 cases had received antiretroviral therapy (ART), and 85% (49,477) of them were continuing to take ARV drugs. In conclusion, the NAPHA was implemented nationwide with comprehensive systems. The reports indicate achievement of expansion of the ART program. Lessons learned from the program initiation and scaling up show local leadership, comprehensive training, adherence, and coordination are essential to program effectiveness and sustainability.

HIV/AIDS care and treatment in three provinces in northern Thailand before the national scale-up of highly-active antiretroviral therapy.

In 2003, Thailand launched a program to place 50,000 persons on highly active antiretroviral therapy (HAART) by the end of 2004, following a series of efforts since the early 1990s to develop comprehensive HIV/AIDS care services. To evaluate existing services and needs in advance of the national HAART scale-up, in 2002 we surveyed 31 hospitals and 389 community health centers in three northern Thai provinces, and interviewed 1,015 HIV-infected patients attending outpatient clinics. All hospitals offered voluntary HIV counseling and testing, 84% provided primary prophylaxis for Pneumocystis carinii pneumonia, 58% for tuberculosis, 39% for cryptococcal meningitis, and 87% had some experience providing antiretroviral therapy. Community health centers provided more limited service coverage. Of patients interviewed, 63% had been diagnosed with symptomatic HIV disease, and of these, 32% reported ever receiving antiretroviral therapy; 51 % of all patients had received a CD4 T-lymphocyte count. Thailand's current national HAART scale-up is being performed in a setting of well-developed hospital-based services introduced over the course of the epidemic.

Evidence of a previously undocumented epidemic of HIV infection among men who have sex with men in Bangkok, Thailand.

BACKGROUND: The HIV prevalence and associated risk behaviours in Thai men who have sex with men (MSM) are unknown. This information is crucial to inform and implement targeted preventive interventions for this population. METHODS: A cross-sectional assessment, using venue-day-time sampling, was conducted. Participants were 1121 Thai men who were 18 years or older, were residents of Bangkok, and reported anal or oral sex with a man during the past 6 months. Oral fluid specimens were tested for HIV antibody. Demographic and behavioural data were collected using an interviewer-administered Palm based automated questionnaire. RESULTS: HIV prevalence was 17.3% (194 of 1121). Mean age was 26.9 years (median 25 years), and university education was completed by 42.5%. Sex with men and women during the past 6 months was reported by 22.3%; sex with a woman ever, 36%; and unprotected sexual intercourse during the past 3 months, 36.0%. Alcohol use during the past 3 months was common (73.7%); drug use was rare (2.5%). Multivariate logistic regression analyses showed lower education, recruitment from a park, self-identification as homosexual, receptive and insertive anal intercourse, more years since first anal intercourse, and more male sex partners to be significantly and independently associated with HIV prevalence. CONCLUSIONS: HIV infection is common among MSM in Bangkok. HIV prevention programs are urgently needed to prevent further spread of HIV in this young and sexually active population.

National program scale-up and patient outcomes in a pediatric antiretroviral treatment program, Thailand, 2000-2007.

BACKGROUND: There are limited reports of public sector scale-up of antiretroviral treatment (ART) for HIV-infected children. We describe patient outcomes for HIV-infected children initiating ART in Thailand from 2000 to 2005. METHODS: ART-naive patients <15 years old initiating ART from January 2000 to December 2005 were included; follow-up was through March 2007. Survival probabilities were estimated with Kaplan-Meier and hazard ratios for death and loss to follow-up (LTFU) with Cox proportional hazards models. RESULTS: Analysis included 3409 children. Median follow-up time was 1.7 years (interquartile range = 1.0-2.5). Median age at ART initiation was 7.3 years, weight-for-age z score was -2.0, CD4% was 5.0%. ART was initiated in 1428 (41.9%) children at regional/university hospitals and in 689 (20.2%) at district/community hospitals. At last visit, 346 (10.1%) were LTFU and 305 (9.0%) had died. Age <1 (P = 0.008), weight-for-age z score <-2.0 (P < 0.001), CD4% <5% (P < 0.001), and clinical stage C (P < 0.001) were associated with death; district/community hospital patients had a lower hazard of death (P = 0.011). Clinical stage C (P = 0.052) and regional/university hospital (P < 0.001) were associated with increased LTFU. CONCLUSIONS: Pediatric ART has been successfully scaled-up in Thailand, including to district/community hospitals. Late entry to care is associated with poorer outcomes, and earlier ART initiation should be prioritized.

National expansion of antiretroviral treatment in Thailand, 2000-2007: program scale-up and patient outcomes.

OBJECTIVE: Thailand began a national antiretroviral (ARV) treatment program in 2000, and all government and some private and university hospitals now provide treatment to eligible HIV-infected patients. We describe program scale-up and patient outcomes from 2000 to 2007. METHODS: Data from 839 hospitals in all 76 provinces of Thailand were included in this analysis. Outcomes were assessed for patients initiating ARV treatment from January 2000 to December 2005. Follow-up data through March 2007 were included; lost to follow-up was defined as >3 months late for a follow-up visit. A Cox proportional hazard model was used to assess risk factors for death; the Kaplan-Meier method was used to estimate survival probabilities. RESULTS: Outcome data are reported for 58,008 patients. Among these, 52.2% were male; at treatment initiation, the median age was 34 years, the median CD4 count was 41 cells per cubic millimeter, and 50.5% had AIDS. The initial regimen was nevirapine and 2 nonnucleoside reverse transcriptase inhibitors for 92.4% of patients; median follow-up time was 1.6 years (interquartile range = 0.8-2.4 years). Lost to follow-up occurred in 8.8% of patients. Overall 1-year survival was 0.89 (95% confidence interval = 0.88 to 0.89). Death was significantly associated with male sex, age >40 years, baseline CD4 count <100 cells per cubic millimeter, symptomatic HIV or AIDS, receipt of services at a district or community hospital, and treatment initiation before 2005. CONCLUSIONS: National ARV treatment programs can be scaled up rapidly with good patient outcomes. Treatment outcomes among patients in Thailand are comparable to those reported in smaller cohorts in other countries, and survival rates have improved since 2004.

Evaluation of a new single-parameter volumetric flow cytometer (CyFlow(green)) for enumeration of absolute CD4+ T lymphocytes in human immunodeficiency virus type 1-infected Thai patients.

Use of the standard dual-platform flow cytometric method for determination of CD4(+) T-lymphocyte counts, which needs both a flow cytometer (FCM) and hematological analyzer, would inevitably lead to increased variability. The development of new single-platform (SP) FCMs that provide direct CD4(+) T-lymphocyte counts for improved assay precision and accuracy have recently attracted attention. This study evaluated one of those systems, CyFlow(green) (Partec), a single-parameter SP volumetric FCM. The performance of CyFlow(green) was compared with those of two reference standard SP microbead-based technologies of the three-color TruCOUNT tube with the FACScan FCM and a two-color FACSCount system (Becton Dickinson Biosciences). Absolute CD4(+) and CD8(+) T-lymphocyte counts in 200 human immunodeficiency virus type 1-seropositive blood specimens were determined. Statistical analysis for correlation and agreement were performed. A high correlation of absolute CD4 counts was shown when those obtained with CyFlow(green) were compared with those obtained with the bead-based three-color TruCOUNT system (R(2)=0.96; mean bias, -69.1 cells/microl; 95% confidence interval [CI], -225.7 to+87.5 cells/microl) and the FACSCount system (R(2)=0.97; mean bias, -40.0 cells/microl; 95% CI, -165.1 to+85.1 cells/microl). The correlation of the CD4(+) T-lymphocyte counts obtained by the two bead-based systems was high (R(2)=0.98). Interestingly, CyFlow(green) yielded CD4(+) T-lymphocyte counts that were 21.8 and 7.2 cells/microl lower than those obtained with the TruCOUNT and the FACSCount systems, respectively, when CD4(+) T-lymphocyte counts were <250 CD4(+) T-lymphocyte counts/microl range or 17.3 and 5.8 cells/microl less, respectively, when CD4(+) T-lymphocyte counts were <200 cells/microl. The single-parameter CyFlow(green) volumetric technology performed well in comparison with the performance of the standard SP bead-based FCM system. However, a multicenter comparative study is needed before this FCM machine is implemented in resource-limited settings.