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BACKGROUND: Incarceration is a known risk for HIV infection in Thai drug users. Through the 1990s, incarceration rates for drug-related offenses rose sharply, whereas HIV prevention and drug treatment in prisons remained limited. METHODS: We assessed HIV and incarceration risks for injection drug users (IDU) and non-IDU in a large treatment center cohort in northern Thailand to investigate HIV and prison risks in this period. We used Thai Bureau of Corrections data to assess incarceration and prevention funds in prisons, 1992-2000. RESULTS: Among 1,865 drug user in the treatment cohort, 503 (27.0%) had ever been jailed. Men (OR 3.3, 95% CI 2.1, 5.2), IDU (OR 6.3, 95% CI 5.1, 7.9), and men who have sex with men (MSM) (OR 3.4, 95% CI 1.8, 6.3) were more likely to have been jailed. Among male IDU who had ever been jailed (N = 272), 15.8% had used drugs in prison. In a multivariate model, incarceration and ever IDU remained independently associated with HIV infection; IDU, MSM behaviors, and harmful traditional practices remained independently associated with having been jailed. From 1992 to 2000, overall alleged narcotics offenses increased from 117,000 to 276,000/year. The number of persons incarcerated for narcotics offenses increased fivefold from 1992 to 1999, from 12,860 to 67,440. For FY 2000, narcotics treatment accounted for 0.06% of the Thai corrections budget, whereas HIV programs in prisons were 0.017%. CONCLUSIONS: Incarceration rates for narcotics offenses have increased sharply in Thailand, whereas prevention has lagged. Having been jailed is an important independent risk for HIV infection among Thai male drug users, especially IDU and MSM. HIV prevention and drug treatment are urgently needed in Thai prisons. [ABSTRACT FROM AUTHOR]

Abstract Background Circumstances surrounding injection initiation have not been well addressed in many developing country contexts. This study aimed to identify demographic factors, sexual behaviors and drug use characteristics related to injection initiation among drug users in northern Thailand. Methods A cross-sectional survey was conducted among 2,231 drug users admitted to the Northern Drug Treatment Center in Mae Rim, Chiang Mai, Thailand, between February 1, 1999 and December 31, 2000. A multiple logistic regression was employed to identify the independent effects from potential risk factors of transition into injection. Results After controlling for other covariates, being 20 years of age or older, single, ever receiving education, urban residence, and having a history of smoking or incarceration were significantly associated with higher likelihood of injection initiation. Multiple sex partners and an experience of sex abuse were associated with an increased risk of injection initiation. Comparing to those whose first drug was opium, individuals using heroin as their initiation drug had greater risk of injection initiation; conversely, those taking amphetamine as their first drug had less risk of injection initiation. Age of drug initiation was negatively associated with the risk of injection initiation: the older the age of drug initiation, the less the risk of injection initiation. Conclusion Injection initiation was related to several demographic factors, sexual behaviors and drug use characteristics. Understanding these factors will benefit the design of approaches to successfully prevent or delay transition into injection.

Background: Prevention of transfusion transmissible HIV and other infections relies on selection of low risk donors and screening donors with sensitive assays. Selection of donors at low risk in developing countries with major heterosexual epidemics of HIV has been difficult. However, the prevalence of HIV among blood donors reflects the control of infection in the community and the self exclusion in part of donors who have previously tested positive. Methods: We evaluated the trends in HIV prevalence among 175,251 blood donors in Chiang Mai, Thailand, between 1990 and 1998. This area has had an explosive HIV epidemic beginning in 1988-1998. These data were useful to monitor the safety of the blood supply and the evolution of the epidemic. Results: The overall HIV prevalence was 3.0% in men and 0.96% in women; prevalence was higher in first time than repeat donors. The HIV prevalence peaked at 4.04% in 1991, leveled off at about 3.5% between 1992 and 1994, then declined to 0.68% in 1998. In 1998 HIV prevalence was similar in men and women and volunteer and repeat donors. Conclusions: There has been a substantial decline in the HIV prevalence among blood donors in N. Thailand in the past few years. This decline probably reflects widespread testing for HIV and a decreased HIV incidence due to an effective public health program to prevent incident infections from exposure during commercial sex the, "100% condom program. More effective exclusion of high risk donors may have contributed to the decline. This is an example of improvement in the safety of blood in a developing country experiencing a major AIDS epidemic. [ABSTRACT FROM AUTHOR]

The RV144 Thai vaccine trial has been the only vaccine study to show efficacy in preventing HIV infection. Ongoing molecular surveillance of HIV-1 in Southeast Asia is vital for vaccine development and evaluation. In this study a novel tool, the multi-region subtype specific PCR (MSSP) assay, that was able to identify subtypes B, C, CRF01_AE for Thailand, other Southeast Asian countries, India and China is described. The MSSP assay is based on a nested PCR strategy and amplifies eight short regions distributed along the HIV-1 genome using subtype-specific primers. A panel of 41 clinical DNA samples obtained primarily from opiate users in northern Thailand was used to test the assay performance. The MSSP assay provided 73-100% sensitivity and 100% specificity for the three subtypes in each genome region. The assay was then field-tested on 337 sera from HIV infected northern Thai drug users collected between 1999 and 2002. Subtype distribution was CRF01_AE 77.4% (n=261), subtype B 3.3% (n=11), CRF01_AE/B recombinant 12.2% (n=41), CRF01_AE/C recombinant 0.6% (n=2), and non-typeable 6.5% (n=22). The MSSP assay is a simple, cost-effective, and accurate genotyping tool for laboratory settings with limited resources and is sensitive enough to capture the recombinant genomes and dual infections., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: DNA vaccines are a promising approach to vaccination since they circumvent the problem of vector-induced immunity. DNA plasmid cytokine adjuvants have been shown to augment immune responses in small animals and in macaques., Methodology/principal Findings: We performed two first in human HIV vaccine trials in the US, Brazil and Thailand of an RNA-optimized truncated HIV-1 gag gene (p37) DNA derived from strain HXB2 administered either alone or in combination with dose-escalation of IL-12 or IL-15 plasmid cytokine adjuvants. Vaccinations with both the HIV immunogen and cytokine adjuvant were generally well-tolerated and no significant vaccine-related adverse events were identified. A small number of subjects developed asymptomatic low titer antibodies to IL-12 or IL-15. Cellular immunogenicity following 3 and 4 vaccinations was poor, with response rates to gag of 4.9%/8.7% among vaccinees receiving gag DNA alone, 0%/11.5% among those receiving gag DNA+IL-15, and no responders among those receiving DNA+high dose (1500 ug) IL-12 DNA. However, after three doses, 44.4% (4/9) of vaccinees receiving gag DNA and intermediate dose (500 ug) of IL-12 DNA demonstrated a detectable cellular immune response., Conclusions/significance: This combination of HIV gag DNA with plasmid cytokine adjuvants was well tolerated. There were minimal responses to HIV gag DNA alone, and no apparent augmentation with either IL-12 or IL-15 plasmid cytokine adjuvants. Despite the promise of DNA vaccines, newer formulations or methods of delivery will be required to increase their immunogenicity., Trial Registration: Clinicaltrials.gov NCT00115960 NCT00111605.

Background: Interleukin (IL)-10 is an immunoregulatory cytokine, levels of which can be influenced by single nucleotide polymorphisms (SNPs) in the promoter. Some, but not all previous studies have shown associations of IL10 SNPs with HIV-1 disease progression, using markers such as viral load or CD4 count. There are few data on IL10 SNP frequencies and HIV-1 disease in regions where non-B HIV-1 subtypes predominate., Objective: To determine genotypes, haplotypes, allele frequencies and associations with markers of HIV-1 disease progression of ILO SNPs., Methods: A new multiplexed PCR-SSP assay to detect IL10 SNPs at positions -1082, -819 and -592 was developed and used to determine genotypes and haplotypes in 244 HIV-1 CRF01_AE-infected northern Thais having a median time since HIV-1 infection of 2.7 years., Results: At position -1082 of IL10, AA genotype and A allele were the most common (87.3% and 93.2%, respectively). The -819 CT and -592 CA genotypes were the most prevalent (44.3%), and -819T and -592A were the most prevalent alleles (64.8%). The ATA/ATA was the most common genotype (42.6%) with the most prevalent haplotype of ATA (64.7%). No associations of any of the three ILO SNPs with CD4+ or CD8+ T cell counts or with viral load were found., Conclusions: This first report of IL10-1082A, -819T and the IL10-592A allele frequencies in HIV-l-infected Thais shows the highest frequencies in HIV-l-infected persons worldwide. The lack of association of IL10 SNPs with CD4+ T cell count and viral load suggest that other genes may influence these markers in HIV-l-infected Thais.

Objectives: To evaluate the survival patterns among adults in Thailand 8-14 years after HIV-1 subtype E (CRF01 A_E) infection., Design: Follow-up for the current vital status of adults who were estimated to have had incident HIV-1 subtype E infection 8-14 years previously., Methods: Data on the survival of a population of HIV-1-infected male blood donors and their seropositive wives was obtained during March-April 2007. These subjects were identified from a subpopulation of 150 individuals whose seroconversion interval was estimated to be less than 2 years and who were enrolled in 1992-1997. National registration, vital records, and death certificates, as appropriate, were obtained and Kaplan-Meier survival curves were constructed for the entire population, for males and females, and for individuals above and equal to or below the median age at infection., Results: The vital status was obtained for 138 of 150 subjects (92%). The overall median survival was 8.2 [95% confidence interval (CI) 7.1-9.4] years. The median survival did not differ significantly between men and women or in those above or below the median age., Conclusion: The median survival of 8.2 years in this population of young adults in Thailand was significantly less than that reported among persons of similar age in high-income countries or in eastern or southern Africa. The survival among individuals in Thailand infected with HIV-1 subtype E appears to be similar to that reported among individuals in Africa infected with HIV-1 subtype D.

Objectives: To estimate survival patterns after HIV infection in adults in low and middle-income countries., Design: An analysis of pooled data from eight different studies in six countries., Methods: HIV seroconverters were included from eight studies (three population-based, two occupational, and three clinic cohorts) if they were at least 15 years of age, and had no more than 4 years between the last HIV-negative and subsequent HIV-positive test. Four strata were defined: East African cohorts; South African miners cohort; Thai cohorts; Haitian clinic cohort. Kaplan-Meier functions were used to estimate survival patterns, and Weibull distributions were used to model and extend survival estimates. Analyses examined the effect of site, age, and sex on survival., Results: From 3823 eligible seroconverters, 1079 deaths were observed in 19 671 person-years of follow-up. Survival times varied by age and by study site. Adjusting to age 25-29 years at seroconversion, the median survival was longer in South African miners: 11.6 years [95% confidence interval (CI) 9.8-13.7] and East African cohorts: 11.1 years (95% CI 8.7-14.2) than in Haiti: 8.3 years (95% CI 3.2-21.4) and Thailand: 7.5 years (95% CI 5.4-10.4). Survival was similar for men and women, after adjustment for age at seroconversion and site., Conclusion: Without antiretroviral therapy, overall survival after HIV infection in African cohorts was similar to survival in high-income countries, with a similar pattern of faster progression at older ages at seroconversion. Survival appears to be significantly worse in Thailand where other, unmeasured factors may affect progression.

Background: The development of an effective HIV-1 vaccine is critical to control the pandemic. A prime-boost HIV-1 vaccine trial assessing safety and immunogenicity was conducted in Thailand as part of an evaluation of candidate regimens for a phase 3 efficacy trial., Methods: ALVAC-HIV (vCP1521), expressing circulating recombinant form 01_AE (CRF01_AE) gp120/subtype B LAI and subtype B Gag/Protease boosted with recombinant envelope oligomeric CRF01_AE gp160 (ogp160) or bivalent CRF01_AE/subtype B gp120 CM235/SF2, was evaluated in a phase 1/II trial of 130 HIV-negative Thai adults., Results: One hundred forty volunteers were enrolled, and 130 completed all safety and immunogenicity visits. Reactogenicity was common but generally mild, and there was no significant difference in the adverse event rate between vaccine and placebo recipients (P = 0.26). There were 7 serious adverse events during the follow-up period, none of which were vaccine related. Cumulative HIV-specific, CD8-mediated, cytotoxic T-lymphocyte responses were observed in 11 (25%) of 44 subjects who received ALVAC boosted by bivalent gp120 and in 5 (11%) of 45 subjects who received ALVAC boosted by ogp160, but these differences were not statistically significant compared with those in placebo recipients (P = 0.62 and P = 0.37, respectively). HIV-specific lymphoproliferative responses were detected in 84% of subunit-boosted vaccine recipients and in 10% of placebo recipients. Neutralizing antibody responses to CRF01_AE and subtype B laboratory strains were seen in 95% of ogp160-boosted and 100% of gp120 B/E-boosted vaccinees, respectively., Conclusions: These 2 different prime-boost regimens seem to be safe and displayed cell-mediated immune responses consistent with those in other trials of canarypox vectors.

In Thailand, the circulating HIV-1 strains include CRF01_AE, subtype B, and their recombinants. Genotyping and full-genome sequencing had previously identified circulating recombinant form CRF15_01B within a cohort of 347 HIV-1-infected individuals enrolled in the Opiate Users Research (OUR) study in northern Thailand. Using an improved MHAbce in six to eight genome regions and archived OUR serum samples, seven strains were identified with a new and complex 01/B recombinant pattern in common, different from that of CRF15_01B. Complete sequencing of three strains, amplified from serum as overlapping half-genomes, confirmed their common recombinant structure, mostly CRF01_AE, but with segments of subtype B in pol and gp41, plus a region of frequent 01/B crossovers in pol. OUR strains 1969P, 2275P, and 2478P were from individuals without direct epidemiological linkage and thus establish CRF34_01B. More comprehensive HIV-1 prevention and treatment programs in IDU can help to limit the growing complexity of HIV-1 strains in Thailand.

Aims: To estimate mortality rates among HIV-negative injecting drug users (IDUs) and non-injecting drug users (non-IDUs), and to assess predictors for mortality among the IDUs., Design: Prospective cohort study in northern Thailand with 2-year follow-up., Setting: IDUs and non-IDUs who were admitted for detoxification treatment for opiate or amphetamine dependence in a regional drug treatment center were screened. After discharge, HIV-negative individuals were followed-up in the community., Participants: A total of 821 HIV-negative drug users [346 IDUs (42%) and 475 non-IDUs, median age = 32; 51% were ethnic minorities]., Measurements: All-cause mortality., Findings: There were 33 deaths over 1360 person-years of follow-up. The all-cause mortality rate was 39 per 1000 person-years among IDUs [standardized mortality ratio (SMR) = 13.9], and was 14 per 1000 person-years among non-IDUs (SMR = 4.4). Among male IDUs, the hazards for all-cause deaths were ethnic minority status [adjusted hazard ratio (HR) = 2.9, 95% CI = 1.2-7.2], incident HIV infection (HR = 2.8, 95% CI = 1.1-7.7) and longer duration of drug injection (HR = 1.07, 95% CI = 1.01-1.14)., Conclusions: The mortality among IDUs is high. Being from an ethnic minority, recent HIV acquisition, and a greater number of years of drug injection are predictors of mortality among the IDUs in this region.

Illicit drug users are commonly infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). We evaluated the prevalence, incidence, and risk behaviors associated with HCV infection in 1,859 drug users in northern Thailand. The HCV prevalence was 27.3%: 86.0% among drug injectors (IDUs) and 5.3% among those who did not inject. Sexual behavior was not significantly associated with HCV among IDUs or drug users who used but didn't inject illicit drugs; only injection behaviors were independently associated with HCV in multivariate analysis. Among men, a history and increasing frequency of injecting drugs, older age, and a history of incarceration were associated with HCV infection. Among 514 opiate users who were HCV and HIV seronegative at baseline, 41 incident HCV infections and 6 HIV infections occurred on follow-up; the HCV incidence was 5.43/100 person-years; it was 44.3/100 person-years in IDUs and 1.9/100 person-years in non-injectors. HCV and HIV among drug users in Thailand are common and primarily associated with injection behavior.

Background: Circumstances surrounding injection initiation have not been well addressed in many developing country contexts. This study aimed to identify demographic factors, sexual behaviors and drug use characteristics related to injection initiation among drug users in northern Thailand., Methods: A cross-sectional survey was conducted among 2,231 drug users admitted to the Northern Drug Treatment Center in Mae Rim, Chiang Mai, Thailand, between February 1, 1999 and December 31, 2000. A multiple logistic regression was employed to identify the independent effects from potential risk factors of transition into injection., Results: After controlling for other covariates, being 20 years of age or older, single, ever receiving education, urban residence, and having a history of smoking or incarceration were significantly associated with higher likelihood of injection initiation. Multiple sex partners and an experience of sex abuse were associated with an increased risk of injection initiation. Comparing to those whose first drug was opium, individuals using heroin as their initiation drug had greater risk of injection initiation; conversely, those taking amphetamine as their first drug had less risk of injection initiation. Age of drug initiation was negatively associated with the risk of injection initiation: the older the age of drug initiation, the less the risk of injection initiation., Conclusion: Injection initiation was related to several demographic factors, sexual behaviors and drug use characteristics. Understanding these factors will benefit the design of approaches to successfully prevent or delay transition into injection.

HIV voluntary counseling and testing (VCT), an important strategy for HIV prevention and care, has been available in all government hospitals in Thailand since 1992. We assessed factors associated with HIV testing, its uptake, and estimates of HIV incidence after HIV testing among male northern Thai injecting drug users (IDUs) admitted for inpatient drug treatment. Participants were interviewed about risk behaviors and HIV testing history before VCT was provided as part of the study. Of 825 IDUs who participated, 36% reported a prior HIV test. Factors associated with prior HIV testing in multiple logistic regression analysis included higher education and having >1 lifetime sex partner. Needle sharing was not associated with prior HIV testing. Of the 298 men with a prior test, 80% reported a negative result on their last prior HIV test, of whom 28% tested positive in our study, leading to an estimated incidence rate of 10.2 per 100 person-years. Fifty-nine percent of the IDUs who reported a prior HIV test stated that they did not receive pre- and/or posttest counseling. HIV incidence among IDUs remains high despite having VCT. Extending HIV prevention and harm reduction programs is urgently needed for IDUs in the region.

Behavioral and social issues were investigated in 363 phase I/II preventive HIV-1 vaccine trial volunteers in Thailand. These issues included risk behavior, HIV knowledge, distress, and social consequences of vaccine trial participation. Data were collected at baseline and at 4-, 8-, and 12-month follow-up visits. Volunteers reported relatively low levels of risk behaviors at baseline and at follow-up. Overtly negative reactions from family or friends were reported by 5.9%. No experiences of discrimination in employment, health care, or insurance were reported. Mean levels of distress were low throughout the trial, and HIV-related knowledge was high, although it was common to consider the possibility of HIV transmission through casual contact. Findings add to the evidence that preventive HIV vaccine trials are feasible in Thailand.

Background: Men who have sex with men (MSM) and who use drugs have shown high HIV risks in Europe, and the Americas. We investigated MSM-drug user demographics, HIV sexual and drug use risks and behaviors in Chiang Mai, northern Thailand to identify prevention targets., Methods: A total of 2005 males aged 13 years and older were enrolled during inpatient drug treatment from 1999-2000 and assessed for HIV, hepatitis C virus (HCV), syphilis, and for demographics and risks by questionnaire. Data were analyzed using chi and multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Of 2005 males in treatment, 1752 (87.4%) had ever had sex, and 66 of 1752 (3.8%) reported ever having sex with another man; mostly Katoey (transgendered male) partners. MSM had higher HIV rates (OR, 2.32; 95% CI, 1.36-3.96) and were younger (P = 0.002); more likely to be Thai (P < 0.0001); better educated (P < 0.0001); had more lifetime sex partners (P < 0.0001), more female partners (P = 0.002), more female paid partners (P < 0.0001), and been paid for sex (P < 0.0001). MSM were more likely to have ever injected (P < 0.0001), sold drugs, been in prison, injected in prison, used heroin, and to have HCV (OR, 2.59; 95% CI, 1.55-4.34)., Conclusions: Northern Thai MSM-drug users are at high HIV and HCV risk. In addition to sex risks with men, they have more sex with women and sex workers than other men, which fits Thai MSM patterns but not Western ones. Prevention must take into account their high rates of substance use and multiple partner types.

A barrier to the appropriate provision of antiretroviral therapy to treat immunosuppressed HIV-infected persons in resource-poor countries is identifying who requires treatment. The World Health Organization (WHO) has suggested using a clinical algorithm combined with a total lymphocyte count (TLC) < 1200 cells/mm as a surrogate for a CD4 count less than 200 cells/mm when it is not possible to measure the CD4 count. We evaluated various TLC levels, anemia, and body mass index and compared our data with the WHO criteria to develop a more sensitive algorithm to predict CD4 counts of < 200 cells/mm and < 350 cells/mm in 839 men and women from Thailand infected with HIV-1 subtype E (CRF01&#95;AE). The December 2003 WHO guidelines had a sensitivity of 34.1% in men and 31.8% in women to detect persons with a CD4 count < 200 cells/mm in this HIV-infected population from Thailand. The use of a TLC < 1500 cells/mm or TLC < 2000 cells/mm combined with anemia or WHO stage II infection doubled the sensitivity to detect persons with a CD4 count < 200 (63.0% in men, 68.2% in women) with less than a 6% decrease in specificity.

Reports on HIV infection and risk behaviors among female drug users in developing countries, particularly in Asia, are limited. In this study, we investigated HIV prevalence and risk factors for HIV infection among 200 women admitted for 21-day inpatient drug detoxification in Chiang Mai, Thailand. Volunteers completed a face-to-face interview using a structured interview, HIV pre-test counseling, specimen collection for HIV and STD tests, and were provided test results and HIV post-test counseling 1 week later. Two-third of participants (68%) were ethnic minorities with no formal education. Overall, 14 (7%) were HIV positive: 25% among 28 heroin injectors and 4.1% among 172 opium or methamphetamine smokers (p<0.001). History of drug injection and sexual abuse were associated with HIV infection. HIV prevention strategies for drug-using women in Thailand should consider both harm reduction strategies for drug use and promoting safer sex measures in a culturally appropriate context.

Background: Human herpesvirus 8 (HHV-8) is associated with Kaposi sarcoma (KS) in patients with acquired immunodeficiency syndrome (AIDS) and KS, classical KS, or endemic KS. Because human immunodeficiency virus (HIV) infections and HIV/AIDS are common in Thailand but KS is very rare (only 0.2% of reported patients with AIDS in Thailand had KS), we determined the HHV-8 seroprevalence among populations who were HIV positive or at risk of HIV infection., Methods: A total of 992 persons from 2 populations underwent testing for lytic antibodies to HHV-8 using an immunofluorescence assay involving a BCBL-1 cell line at serum dilutions of 1 : 50 and 1 : 100. Serum specimens with positive results were titered to end points. Subjects included approximately 400 married couples in which the husband was HIV positive and the wife was HIV positive (200 couples) or HIV negative (200 couples). In addition, 200 HIV-negative men from a sexually transmitted diseases (STD) clinic were studied., Results: The antibody prevalence was 24.2% in the total population. The prevalence was higher among HIV-negative men (13.0%) but was similar among HIV-positive women (27.9%) and HIV-negative women (23.8%). The HHV-8 seroprevalence among wives whose husbands were HIV-1 positive did not differ according to their husband's HHV-8 status. There was no association between HHV-8 seroprevalence and reported sexual behavior or STD history., Conclusion: Despite the rarity of KS among patients with AIDS in Thailand, HHV-8 infections are common and do not appear to be frequently transmitted sexually in these populations.

Cross-sectional laboratory data were used to model the patterns of total lymphocyte count and lymphocyte subpopulation counts among persons with chronic HIV-1 subtype E (CRF01&#95;AE) infection during the 6.5 years preceding death. The data cover 331 HIV-infected decedents from a heterosexual HIV transmission study of 590 northern Thai couples enrolled in 1992-1998. From blood collected at enrollment, the lymphocyte phenotypes (CD3, CD8, CD4, natural killer, and B cells) were stained using two-color monoclonal antibody combinations and quantified by flow cytometry. Piecewise linear splines modeled the associations between lymphocyte levels and time before death. Mean CD3, CD8, and B cell levels showed no temporal associations from 6.5 to 2 years before death, but each declined significantly during the 2 years before death. CD3 levels declined 31.0% [95% confidence interval (-40.3%, -19.8%)] and CD8 levels declined 24.6% (-35.4%, -13.5%) annually in the 2 years prior to death. In contrast, CD4 and NK cell levels declined little from 6.5 to 4.5 years before death but declined significantly over the 4.5 years prior to death. CD4 levels declined 22.1% (-29.2%, -12.0%) annually from 4.5 to 2 years prior to death and 63.7% (-72.3%, -53.6%) annually over the remaining 2 years. Similar lymphocyte patterns have been reported in U. S. and European populations with HIV-1 subtype B infection.

CRF01&#95;AE and subtype B have dominated the HIV-1 epidemic in Thailand since 1989. We reported a new circulating recombinant form of HIV-1, CRF15&#95;01B, as well as other unique CRF01&#95;AE/B recombinants among prevalent HIV infections in Thailand. We sought to study this challenging molecular picture through assessment of subtypes among recent HIV-1 seroconverters in northern Thai drug users. A total of 847 HIV-1 seronegative drug users (342 IDU and 505 non-IDU) were enrolled, from 1999 to 2002, in a prospective study; 39 HIV-1 incident cases were identified and characteristics were collected. The overall HIV-1 incidence rate was 2.54/100PY, but it was 10.0/100PY among male IDU. HIV was strongly associated with injection history; 38 of 39 seroconverters gave a history of IDU. A near full-length genome of HIV-1 was recovered by PCR amplification and sequenced from peripheral mononuclear cell extracted DNA of 38 seroconverters. Phylogenetic analysis revealed that 33 (86.8%) were CRF01&#95;AE and 5 (13.2%) were CRF01&#95;AE/B recombinants. These recombinants had different structure but shared some common breakpoints, indicating an ongoing recombination process. Recombinant infection increased with year of sampling (0 to 57.1%). The molecular epidemiology of HIV-1 among drug users in northern Thailand has thus entered a new era. CRF01&#95;AE remains predominant while pure subtype B is becoming rare, and now a substantial component of the epidemic. These findings support the need for CRF01&#95;AE and subtype B components in clade-matched vaccine strategies for Thai phase III trials. Ongoing molecular surveillance of circulating HIV-1 strains is imperative for the evaluation of HIV vaccine efficacy.

We evaluated a quantitative enzyme immunoassay (trak-C) for hepatitis C virus core antigen (HCV core Ag) by testing serum specimens from 820 injection drug users in Thailand with anti-HCV antibodies. The HCV genotypes in this population include genotypes 3 and 6, which have not been extensively tested with this assay. Among these specimens, 629 (76.7%) yielded positive results, with HCV core Ag concentrations predominantly spanning (35.7%) or above (58.2%) the measurable range of 1.5 to 100 pg/ml. To assess reproducibility, we retested 30 specimens representing six core Ag ranges; the mean coefficient of variation for each range was < or = 9.7% (highest for 1.5 to 25 pg/ml). We also tested 204 specimens of the 820-specimen set for HCV RNA: while 146 (71.6%) were core Ag positive, 168 (82.4%) had detectable HCV RNA, of which 96% were typeable as genotype 3 (39%), 1 (31%), or 6 (26%) by nested reverse transcription-PCR. Among RNA-positive specimens, 86.9% had core Ag; 94% of the RNA negatives were core Ag negative. While there was no apparent bias for detecting core Ag representing the tested genotypes, median quantified results were higher for types 1a and 6 than for genotype 3 (P = 0.01); similarly, the median core Ag concentration was higher in HCV-human immunodeficiency virus-coinfected subjects than in HCV-monoinfected subjects. Our results demonstrated a good correlation between core Ag and HCV RNA in this population with high frequencies of genotypes 3 and 6. Because most core Ag concentrations were greater than those in the measurable range, we recommend a 10-fold dilution of the specimen before quantification. Reproducibility, low technical requirements, and high throughput should make this assay useful for clinical or research monitoring of HCV levels during active infection.

HIV-1 subtype B and CRF01&#95;AE have been in circulation in Thailand and Southeast Asia for more than a decade. Initially separated by risk group, the two strains are increasingly intermixed, and two recombinant strains of essentially reciprocal structure have been recently reported. Here we identify additional CRF&#95;01B recombinants and provide the evidence that HIV-1 strains now pass freely between the two high-risk populations. HIV isolates that showed discordance between CRF01&#95;AE and subtype B in multi-region genotyping assays were selected for the study. They were drawn from 3 different cohorts in Thailand representing different risk behaviors and demographic characteristics: a drug user cohort in the north, a family planning clinic attendee cohort in the southeast, and a cohort study of the mucosal virology and immunology of HIV-1 infection in Thailand. The DNA from these isolates was PCR amplified to recover the full HIV-1 genome and subjected to sequencing and phylogenetic analysis. We establish that one particular CRF&#95;01B recombinant, with the external envelope of subtype B and the rest of the genome from CRF01&#95;AE, is circulating widely in Thailand. Termed CRF15&#95;01B (also referred to as CRF15), the strain was primarily heterosexually transmitted, although injecting drug use (IDU) also played a role. In aggregate data from the studies, CRF15 constituted 1.7% of all HIV-1 infections (95% confidence interval 0.5-4.4%) and was dispersed widely in the country. The previously separate heterosexual and IDU epidemics have apparently been bridged by a new CRF. The entry of CRF15 into the mainstream of the epidemic signals new complexity in the long stable molecular picture in Thailand. These recombinants must be considered in ongoing or projected efficacy evaluations of HIV-1 vaccines and antiviral therapies.

The authors sought to determine sociodemographic and sexual and drug use risk factors for HIV infection among drug users in northern Thailand adjacent to the Golden Triangle. The authors enrolled patients admitted for inpatient drug detoxification at one treatment center in northern Thailand and studied HIV risks and prevalence using an interviewer-administered questionnaire and serum collection with HIV pretest and posttest counseling. Between February 1, 1999 and January 31, 2000, 1865 patients admitted for opiate and methamphetamine dependence completed study procedures. Overall HIV prevalence was 10.3%: 30.0% among 513 injection drug users (IDUs) and 2.8% among non-IDUs (OR = 14.8, 95% CI: 10.2, 21.6). HIV seroprevalence was 2.4% among exclusive methamphetamine users (98% of whom are non-IDUs) and 3.4% among opium smokers. Injection drug use was the dominant risk factor in multivariate models. Although Thailand is widely recognized as having a successful national response to the heterosexual HIV epidemic, seroprevalence in IDUs remains high. Despite a sharp increase of non-IDUs admitted to the drug treatment center, HIV infection and risks remained high among IDUs in northern Thailand. HIV prevention campaigns need to focus on IDUs and to implement harm reduction strategies to reduce transmission to IDUs and further contain the HIV epidemic in Thailand.

Background: Thailand's epidemic of HIV infection, which began in 1988, has primarily involved heterosexual transmission of the virus. This study describes changes in prevalence of HIV and other infectious diseases among blood donors in northern Thailand from 1990 through 2001., Study Design and Methods: Serologic screening results and demographic data were analyzed from 276,066 donors screened at two blood collection facilities in Chiang Mai, Thailand, from 1990 through 2001., Results: The HIV prevalence peaked in 1991 to 1993 at 4.04 percent and then declined to 0.38 percent in 2001. The overall prevalence of HIV infection was 2.16 percent; HIV prevalence was higher among male (2.24%) than among female (0.64%) donors, in first-time donors, and in replacement volunteer donors. The majority of the donors were men and first-time donors throughout this study. The prevalence of antibodies to syphilis decreased significantly in both men and women. However, the prevalence of antibodies to HCV and HBsAg were stable., Conclusions: The declining HIV prevalence from 1990 through 2001 among blood donors in two large blood banks in northern Thailand indicates significant progress toward recruitment of a safer donor population in a developing country despite a major HIV and AIDS epidemic involving the general population.

Eighteen highly exposed but persistently seronegative (HEPS) women (HW) and their human immunodeficiency virus (HIV) type 1-seropositive male partners were studied for HIV-specific T cells and other host factors. Circulating HIV-specific T cells were measured by interferon-gamma enzyme-linked immunospot assays, using recombinant vaccinia virus vectors expressing HIV proteins. Nine (50%) of the HW and all HIV-seropositive persons had HIV-specific T cell responses. Only 2 (22%) of the HEPS responders recognized Env, compared with 94% of HIV-seropositive persons. A high percentage (75%) of the HW with HIV-specific T cell responses reported recent HIV exposure. Remarkably, however, long-lived HIV-specific T cells were detected in 2 HW who had an extended period (>3.9 years) of no HIV exposure. These findings have important implications for HIV vaccine design.

We evaluated the association between HIV-1 RNA copies/mL in men and heterosexual transmission to their female partners among 493 couples in Thailand. Husbands were identified as HIV-positive when they were screened as blood donors; nearly all were infected with HIV subtype E. Wives had no known risks for HIV infection other than sex with their husbands. In multivariate analysis, each log10 increment of HIV RNA in the man was associated with an 81% increased rate of HIV transmission to his wife (odds ratio = 1.81, 95% confidence interval: 1.33-2.48). No transmission occurred at viral loads below 1094 copies/mL, and a dose-response effect was seen with increasing viral load in the man. In multivariate analysis, a history of a sexually transmitted disease in the man or woman, longer duration of hormonal contraceptive use, and the woman's onset of sexual activity at less than 20 years of age were also associated with increased seropositivity of the wife.

HIV-1 coreceptors CCR5 and CXCR4 play an important role in viral entry and pathogenesis. To better understand the role of viral tropism in HIV-1 transmission, we examined the coreceptor utilization of viral isolates obtained from men enrolled in a study of heterosexual transmission in northern Thailand. Viral isolates were obtained from HIV-1-positive males who had either HIV-1-infected spouses (RM; n = 5) or HIV-1-uninfected spouses (HM; n = 10). Viral isolates from 1 of the 5 RM males and 2 of the 10 HM males were CCR5 tropic, whereas isolates from 3 RM males and 6 of the HM male isolates were CXCR4 tropic. Of the nine X4-tropic isolates, seven also used at least one of the following coreceptors: CCR8, CCR1, CCR2b, or CX3CR1, and none employed CCR5 as an additional coreceptor. More importantly, three isolates, RM-15, HM-13, and HM-16 (one from a transmitter and two from nontransmitter), did not infect GHOST4.cl.34 cells expressing any of the known coreceptors. Further analysis using MAGI-plaque assays, which allow visualization of infected cells, revealed that RM-15 had low numbers of infected cells in MAGI-R5 and MAGI-X4 cultures, whereas HM-13 and HM-16 had high levels of plaques in MAGI-X4 cultures. Replication kinetics using activated lymphocytes revealed that these three isolates replicated in CCR5(+/+) as well as CCR5(-/-) peripheral blood mononuclear cells, suggesting that these isolates did not have an absolute requirement of CCR5 for viral entry. All three isolates were sensitive to the X4-antagonistic compounds T-22 and AMD3100. Analysis of the C2V3 region did not reveal any significant structural differences between any of the Thai subtype E isolates. Thus, there was no association between the pattern of coreceptor usage and transmissibility among these subtype E HIV-1 isolates.

Fifty-two human immunodeficiency virus type 1, seronegative Thai adults from the community were enrolled in a double-blind, placebo controlled, phase I/II trial of HIV SF2 gp120/MF59 vaccine to determine the safety and immunogenicity of this recombinant, B clade, HIV envelope protein vaccine. Twenty-six subjects were enrolled at each of two sites in Thailand, Bangkok and Chiang Mai. Twelve subjects received placebo and 40 subjects received vaccine (50 microg). Subjects were immunized according to one of two schedules, 0, 1 and 4 or 0, 1 and 6 months. The frequency of adverse reactions was not different between placebo and vaccine subjects, nor between immunization schedules. Of vaccinees, all developed high-titer binding antibody to the immunogen (rgp120), 39 developed neutralizing antibody (NA) responses against homologous virus (HIV-1(SF2)), and 22 developed NA against heterologous virus (HIV-1(MN)). No subject demonstrated intercurrent HIV infection, however screening EIA reactivity occurred in 27% of recipients. Thus, this candidate HIV vaccine was found to be safe and immunogenic in Thai adults, laying the foundation for development of a subtype E construct in this population.

The heterosexual transmission of subtype E human immunodeficiency virus type 1 (HIV-1) infection was evaluated in 467 couples in Thailand in whom the man was HIV-1 positive and the woman had no risk factors for HIV other than sex with her infected partner. At baseline, 216 (46.3%) of the 467 women were positive for HIV-1; prevalence of HIV among women was 52.2% when their male partners had CD4+ lymphocyte counts of <200 cells/microL, 45.9% in women whose partners had counts of 200-499 micro/L, and 39.2% in women whose partners had counts of >/=500/microL. Women were twice as likely to be HIV positive if their partners had a history of a sexually transmitted disease (STD); however, their HIV prevalence was 29% among couples who had no STD history. It appears that female partners of men infected with subtype E HIV-1 are at high risk of infection even when the man's CD4+ cell count is relatively high. A high rate of STDs may contribute significantly to this risk [corrected].

Objective: To describe risks for HIV transmission from male blood donors to their regular female sex partners in Chiang Mai, Thailand., Design: Cross-sectional study., Methods: From March 1992 through September 1995, 405 HIV-seropositive male blood donors (index cases) and their regular female partners were enrolled in the study. Women with risk factors for HIV infection other than sexual contact with the index male were excluded. Couples were interviewed and examined; specimens were collected for laboratory analysis., Results: Overall, 46% of the 405 women enrolled were HIV-positive. Ninety-eight per cent of male index cases had a history of sex with a female prostitute; 1.5% reported always using condoms with their regular partner. History of sexually transmitted disease (STD) and swollen inguinal lymph nodes in the female partner were associated with an increased risk of HIV infection in the female. History in the female of genital herpes [odds ratio (OR), 3.46; 95% confidence interval (CI), 1.50-8.78], gonorrhea or chlamydia infection (OR, 2.71; 95% CI, 1.39-5.53), and stable relationship of longer than 24 months (OR, 2.28; 95% CI, 1.02-5.09) were associated with an increased risk of HIV infection in the female. Consistent condom use in the past 2 years (OR, 0.10; 95% CI, 0.01-0.79) was associated with a decreased risk of HIV infection in the female., Conclusions: Married women in northern Thailand who appear otherwise to be at low risk for HIV infection may be exposed to this virus by their husbands. High rates of sex with commercial sex workers among men and low use of condoms within stable relationships may be important factors promoting the transmission of HIV in married couples. Programs to increase the regular use of condoms among married couples could be an important public health intervention to prevent transmission of HIV and other types of STD in northern Thailand.

Objectives: To determine the age- and sex-specific prevalence of HIV-1 infection in a general ambulatory population in northern Thailand in 1990 and 1992, and the incidence of HIV-1 infections between 1990 and 1992., Design: Health fairs were held in five villages in Chiang Mai province in northern Thailand between December 1989 and January 1990 and again in January 1992. Participation of all village residents was encouraged. Villagers were offered testing for serological markers of hepatitis B virus (HBV) infection and free HBV vaccine was made available to susceptible individuals., Methods: Sera from the two surveys were linked and coded by demographic characteristics (age group and sex). Individual identifiers were removed and the sera tested for HIV-1 antibodies by enzyme-linked immunosorbent assay with Western blot confirmation., Results: In 1990, 21 out of 1161 (1.8%) individuals were HIV-1-seropositive; the infection rates were 3.3% in men and 0.5% in women. In 1992, 44 out of 956 (4.6%) individuals were HIV-1-seropositive. Among people included in both surveys the 2-year incidence was 2.0% in women and 4.1% in men (annual incidence, 1.0 and 2.05%, respectively); however, among men over the age of 14 years the 2-year incidence was 6.3%, whereas among women of this age the 2-year incidence was 1.8% (annual incidence, 3.15 and 0.9%, respectively). Among men, incident HIV-1 infections were common, even among those aged 50 years or more., Conclusions: Infections with HIV-1 are disturbingly frequent and increasing among adult populations in semi-rural areas of northern Thailand. In order to contain further spread of the epidemic public-health strategies targeted to the general public, including those in rural areas, will be needed.

To examine the pathogenesis of type 1 (reversal) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 10 patients with reactions, 24 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells and Tac-peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During reversal reactions: a) the lesions contained an increased number and percentage of CD4+ (T-helper) cells; b) Tac-peptide levels were elevated in half of the lesions; c) the increases in Tac peptide and CD4+ cells were directly correlated; and d) systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population. These findings were localized to the skin, and do not represent simple filtration of these components from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of CD4+ cells, is an important feature of reversal reactions, and may be an intermittent or cyclic phenomenon during the reaction. Findings in active patients without reactions are consistent with the hypothesis that differing states of immunologic equilibrium have been established in different portions of the leprosy spectrum. In reversal reactions we may, therefore, be examining immunologic processes set in motion when a pre-existing equilibrium has been upset by spontaneous, natural events. The mechanism of such spontaneous changes in immunity in leprosy is of considerable interest, not only to understand the reaction, but also to examine the underlying determinants of delayed-type hypersensitivity and cell-mediated immunity in leprosy and the potential for artificially manipulating these responses, as proposed with vaccines or immunotherapy.

Antibodies of IgM, IgG and IgA classes against M.leprae specific antigens (PGL-I, ND-O-BSA, and NT-O-BSA) were determined in the sera of 80 leprosy patients (28 untreated, 34 treated lepromatous and 18 tuberculoid), 25 tuberculosis patients and 33 normal individuals of Northern Thailand. No strong distinction in reactivity could be found between the three antigens. The IgM antibody assay yielded more positive results than assays for IgG and IgA. It was found that the positivity rates of IgM antibodies to all three antigens were highest in untreated lepromatous leprosy (82%). In tuberculoid leprosy, the positivity rates of IgM, IgG and IgA to the antigens were more variable, ranging from 22 to 50 percent. Patients with tuberculosis and normal individuals did not produce IgM antibodies against the antigens. The results suggested that the determination of IgM against the three antigens is a more sensitive and specific test for active leprosy than those of IgG and IgA. The relationship between the duration of treatment and IgM antibody levels in lepromatous leprosy (LL) was studied. Untreated LL patients had significantly higher IgM and IgA antibody levels than treated patients. There was no difference in IgG antibody levels between the two groups, and the levels of both groups were higher than normal controls. Serial determination of IgM antibodies in 7 LL patients revealed that treatment was strongly associated with progressive decrease in IgM antibody levels against all three antigens.

A patient with chronic vulvo-vaginitis due to Trichomonas vaginalis, and obstructive uropathy associated with renal calculi, developed a perinephric abscess following trauma incurred in a motorcycle accident. T. vaginalis was seen on smear and cultured from the purulent drainage from the perinephric abscess. Although T. vaginalis is commonly pathogenic only to the lower genito-urinary system, the upper urinary tract may very rarely be involved by ascending infection. If this protozoan spreads to extraluminal sites the inflammatory potential is marked, as has been found in animals with experimental infection. Examination of a fresh smear of pus may be critically important in the diagnosis of closed-space infections of unknown etiology.

The cellular contents of blisters induced by suction over new, uncomplicated leprosy lesions, and in the skin of cured, control patients, have been examined with enzyme- and immuno-histochemical staining over a period of 4 days. The total cellularity of the blisters varied over a wide range, not correlated with the type of leprosy. Mononuclear cells predominated at all times studied, with nearly equal percentages of monocytes and T lymphocytes. The T-helper: suppressor ratio was significantly greater in BT than in BL and LL lesions at 48 hr. Suction blisters offer a painless, quantitative, reproducible, multiple-sampling method for obtaining cells from the cutaneous infiltrates of leprosy for phenotyping or functional analysis.

Carbohydrate metabolism, as assessed by the intravenous glucose tolerance test (i.v.-GTT), was studied in 19 healthy, non-lactating women who received injectable contraceptives containing either medroxyprogesterone acetate (DMPA) (10 subjects) or norethisterone enanthate (Net-En) (9 subjects). Tests were made prior to treatment and at intervals over a period of 15 months thereafter. Results obtained indicate that carbohydrate metabolism is not impaired by either of the two progestogens, and neither pyruvate nor cortisol concentrations changed significantly over the period of observation. However, the insulin release in response to glucose loading underwent interesting alterations during treatment. These abnormalities returned promptly to normal after withdrawal of treatment.

Adrenal function and its reserve capacity were studied in eighteen healthy non-lactating women who received depot-medroxyprogesterone acetate (DMPA: 9 subjects) and norethisterone enanthate (NET-EN: 9 subjects) as long-acting injectable contraceptives. Methodological assessments included: (i) morning fasting concentration of serum cortisol; (ii) diurnal variation of adrenal corticol activity as evidenced by cortisol concentration in serum samples taken at 0700 and 1600 hours; (iii) urinary free cortisol excretion; and (iv) cortisol response to insulin-induced hypoglycaemia. None of these assessments was significantly altered by contraceptive administration. This finding indicates that the subject's ability to release cortisol in response to a stressful situation, as well as to normal day-to-day activity, was not impaired by these contraceptive steroids.