Kittipong Rungruengthanakit

Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe

Background:An association has been demonstrated between herpes simplex type 2 (HSV-2) and HIV infection among men, but prospective studies in women have yielded mixed results. Objective:To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries. Design:Prospective cohort study. Methods:HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15–24 months among 4531 sexually active, HIV-uninfected women aged 18–35 years from Uganda and Zimbabwe. The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model, adjusted for covariates. Results:HSV-2 seroprevalence at enrollment was 52% in Uganda and 53% in Zimbabwe; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Uganda and Zimbabwe, respectively. In Uganda, the hazard ratio (HR) for HIV was 2.8 [95% confidence interval (CI), 1.5–5.3] among women with seroprevalent HSV-2 and 4.6 (95% CI, 1.6–13.1) among women with seroincident HSV-2, adjusted for confounding. In Zimbabwe, the HR for HIV was 4.4 (95% CI, 2.7–7.2) among women with seroprevalent HSV-2, and 8.6 (95% CI, 4.3–17.1) among women with seroincident HSV-2, adjusted for confounding. The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42% in Uganda and 65% in Zimbabwe. Conclusions:HSV-2 plays an important role in the acquisition of HIV among women. Efforts to implement known HSV-2 control measures, as well as identify additional measures to control HSV-2, are urgently needed to curb the spread of HIV.

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.

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.

HIV incidence and risk behaviours after voluntary HIV counselling and testing (VCT) among adults aged 19-35 years living in peri-urban communities around Chiang Mai city in northern Thailand, 1999.

The Thai government began HIV voluntary counselling and testing (VCT) in all provinces in 1992. We evaluated HIV incidence after participants utilized VCT and its effect on risk behaviours among northern Thai adults aged 19–35 years. A total of 924 men and 1,327 women volunteered to participate in the study. Subjects were counseled, interviewed (socio-demographic, HIV risk behaviour, and HIV testing history), and tested for HIV infection at baseline and at 6 months follow-up. All participants were provided group pre-test counselling; HIV test results were provided in individual confidential post-test counselling. Overall, 329 of 391 men and 621 of 669 women who reported a prior HIV test before participating in our study reported negative results at the previous test. Of these, nine men and 13 women tested positive at baseline, giving incidence rates of 1.04 and 0.69 per 100 person years (PY), respectively. Recent risk behaviour was rare; as a result, the effects of VCT on risk behaviours among the study participants could not be determined. The HIV incidence after VCT among this study population is substantial. Studies to investigate factors associated with HIV incidence among VCT clients could provide insights for more effective HIV prevention.

Specific Antibody Responses to Vaccination with Bivalent CM235/SF2 gp120: Detection of Homologous and Heterologous Neutralizing Antibody to Subtype E (CRF01.AE) HIV Type 1

HIV-1 CRF.AE-01 (formerly subtype E) infection is highly prevalent in Southeast Asia. Despite success with public health measures, the development of an effective CRF01.AE vaccine is critical to the control of this epidemic. Sera from the open-label arms of the first clinical trial of a bivalent HIV gp120 SF2/CM235 (subtypes B and CRF.AE-01, respectively) vaccine were evaluated for the presence of gp120-specific binding (BAb) and neutralizing antibody (NAb). Twelve pre- and postvaccination sera pairs were tested for CM235 BAb; anti-gp120 CM235 BAb was found in all postvaccination samples. The 12 pre- and postvaccination (1 month after third vaccination) serum pairs were evaluated in several neutralization formats: heterologous T cell line adapted (TCLA) NP03/H9, homologous CM235/PBMC, CM235/dendritic cell, and CM235M4-C4.6/A3R5. A3R5 is a CCR5+ T cell line, and CM235M4-C4.6 is the homologous CM235 virus adapted to growth in A3R5 cells. All volunteers developed BAb, but meaningful NAb was not demonstrable against primary isolate CM235. Using the TCLA CRF01.AE virus NP03 in H9 cells, 9 of 12 persons had NAb with a geometric mean titer (GMT) of 46. The CM235M4-C4.6 virus in A3R5 cells also detected NAb in 9 of 12 persons, with a GMT of 41. CM235M4-C4.6/A3R5 detected NAb in two persons with negligible NAb to NP03/H9 and vice versa. Whether the NAb detected by the CM235M4-C4.6/A3R5 system is qualitatively different from those in more traditional NP03/H9 assays will require further study.

High Rates of Transmission of Subtype E Human Immunodeficiency Virus Type 1 among Heterosexual Couples in Northern Thailand: Role of Sexually Transmitted Diseases and Immune Compromise

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 mans CD4+ cell count is relatively high. A high rate of STDs may contribute significantly to this risk [corrected].

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.