Vinai Suriyanon

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 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.

Drug use, increasing incarceration rates, and prison-associated HIV risks in Thailand.

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.

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.

HIV prevalence and risks among injection and noninjection drug users in northern Thailand: need for comprehensive HIV prevention programs.

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.

A phase I/II trial of HIV SF2 gp120/MF59 vaccine in seronegative Thais.

Abstract 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 μg). 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-1SF2), and 22 developed NA against heterologous virus (HIV-1MN). 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.

Risk factors for HIV-1 transmission from HIV-seropositive male blood donors to their regular female partners in northern Thailand.

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.

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 χ2 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.

Methamphetamine users in northern Thailand: changing demographics and risks for HIV and STD among treatment-seeking substance abusers.

Our objective was to determine sociodemographic, sexual and drug-use-related risk factors among methamphetamine (MA) users presenting for drug treatment in northern Thailand. Patients admitted for drug detoxification for MA and other drugs were studied cross-sectionally for risk factors associated with substance abuse and blood-borne and sexually transmitted pathogens. In all, 1865 (200 women) patients treated for MA, opiate, and mixed substance abuse between 1 February 1999 and 31 January 2000 completed all study procedures. Among 1865 participants, 750 (40.2%) were admitted for MA detoxification and 1115 (59.8%) for opiate (heroin, opium, or both) treatment. MA users were significantly younger, better educated, more likely to be Thai than highland ethnic minorities, and had significantly different sexual risks and sexually transmitted disease rates, including lower syphilis seropositivity and higher chlamydial prevalence, than persons admitted for opiate or mixed drug treatment. For those who reported MA use only, use by injection was rare and HIV infections significantly less common than among all other drug users. Thailand is undergoing an epidemic of MA use. These young users are a strikingly different population from opiate/heroin users in northern Thailand. MA users had higher rates of chlamydia infection than opiate users, reflecting their young age, and HIV rates in this population were lower than injecting drug users, but still elevated. MA use is a serious public health problem in Thailand and both improved prevention and treatment methodologies are urgently needed.

Broad Human Immunodeficiency Virus (HIV)–Specific T Cell Responses to Conserved HIV Proteins in HIV-Seronegative Women Highly Exposed to a Single HIV-Infected Partner

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.