Frequencies of IL10 SNP genotypes by multiplex PCR-SSP and their association with viral load and CD4 counts in HIV-1-infected Thais.

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.

Identification of CRF34_01B, a second circulating recombinant form unrelated to and more complex than CRF15_01B, among injecting drug users in northern Thailand.

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.

Predictors of mortality among injecting and non-injecting HIV-negative drug users in northern 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.

Hepatitis C infection among drug users in northern Thailand.

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.

Risk factors associated with injection initiation among drug users in Northern Thailand.

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.

High HIV, hepatitis C and sexual risks among drug-using men who have sex with men in northern 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.

HIV infection among female drug users in Northern Thailand.

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.

An effective tool for identifying HIV-1 subtypes B, C, CRF01_AE, their recombinant forms, and dual infections in Southeast Asia by the multi-region subtype specific PCR (MSSP) assay.

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.

Seroprevalence of human herpesvirus 8 infection in Northern Thailand.

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.

Lymphocyte homeostasis in HIV-infected northern Thais.

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_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.

The changing molecular epidemiology of HIV type 1 among northern Thai drug users, 1999 to 2002.

CRF01_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_01B, as well as other unique CRF01_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_AE and 5 (13.2%) were CRF01_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_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_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.

Coreceptor utilization of HIV type 1 subtype E viral isolates from Thai men with HIV type 1-infected and uninfected wives.

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.

A new circulating recombinant form, CRF15_01B, reinforces the linkage between IDU and heterosexual epidemics in Thailand.

HIV-1 subtype B and CRF01_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_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_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_01B recombinant, with the external envelope of subtype B and the rest of the genome from CRF01_AE, is circulating widely in Thailand. Termed CRF15_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.

Safety and immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and/or IL-15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults.

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.

Survival of blood donors and their spouses with HIV-1 subtype E (CRF01 A_E) infection in northern Thailand, 1992-2007.

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.

Time from HIV seroconversion to death: a collaborative analysis of eight studies in six low and middle-income countries before highly active antiretroviral therapy.

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.

A phase 1/2 comparative vaccine trial of the safety and immunogenicity of a CRF01_AE (subtype E) candidate vaccine: ALVAC-HIV (vCP1521) prime with oligomeric gp160 (92TH023/LAI-DID) or bivalent gp120 (CM235/SF2) boost.

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.

HIV voluntary counseling and testing and HIV incidence in male injecting drug users in northern Thailand: evidence of an urgent need for HIV prevention.

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.

Predictors of low CD4 count in resource-limited settings: based on an antiretroviral-naive heterosexual thai population.

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_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.

Behavioral and social issues among volunteers in a preventive HIV vaccine trial in Thailand.

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.