In 1992 the Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, collaborated with the Phramongkutklao Army Medical Center to set up the Joint Clinical Research Center (JCRC). The purpose of the Center is to conduct clinical research in support of HIV vaccine development and testing. To date, eight HIV vaccine-related research protocols have been conducted at the JCRC, involving 1,668 volunteers. The JCRC has been, and continues to be, a key site for the transfer of clinical trial expertise to new sites at universities, government clinics and hospitals in Thailand and other countries. Overall rates of follow-up have been excellent, while protocol violations and data clarification errors have been minimal.

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.

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.

Behavioral and social issues were investigated in phase I/II preventive HIV vaccine trial volunteers in Thailand. These included risk behavior, HIV knowledge, distress, and social experiences associated with trial participation. Data were collected at baseline and at 4- and 8-month follow-up visits. Volunteers reported relatively low levels of risk behaviors at baseline and at the follow-up visits. About one fifth reported overtly negative reactions from family or friends. No problems with discrimination in employment, health care, or insurance were reported. Findings add to the evidence suggesting the feasibility of phase I/II prophylactic HIV vaccine trials with low-risk volunteers in Thailand.

Persons attending sexually transmitted disease clinics at three sites in Thailand were recruited to participate in a I-year study of HIV-1 incidence. Between September 1995 and February 1996, 31% (371 of 1205) of eligible men and 24% (161 of 659) of eligible women agreed to participate. At enrollment, HIV-1 seropositivity was 3.8% among men and 2.5% among women. Follow-up of the 514 participants who were seronegative at baseline was 78% at the 12-month visit. During the study period, 53% of men reported 2 or more sexual partners, 31% reported sex with a commercial sex worker (CSW), and 33% with a casual partner. Of those visiting CSWs, 72% reported consistent condom use. Among women, 11% reported 2 or more sexual partners. Decreased HIV risk behaviors among men were observed during the study. Four incident infections occurred in men (1.4/100 person-years, 95% confidence interval [CI] = 0.4-3.6) and none among women. Based on the observed HIV-I incidence, HIV vaccine efficacy trials in such populations would have to be larger than previously planned or more selective of high risk subgroups for recruitment.

Correlates of behavior associated with HIV exposure risk were evaluated in cross-sectional data from 3,839 Royal Thai Army (RTA) recruits whose birthplaces and residences were located away from Thailand's main HIV epicenter. Participants were generally 21 years old, unmarried, educated at the primary school level, and previously had been engaged in agriculture or unskilled labor. HIV prevalence in the sample was 1.8%. Condom use with commercial sex workers (CSW) was less than universal, and a small subset of men emerged who had multiple categories of partners. Nonetheless, CSW patronage appeared lower than in early studies in the Thai epicenter of the Upper North, and the venues patronized generally were not low-cost, high-turnover brothels. Sexual experience with girlfriends was more frequent than CSW experience, and the rate of condom use with girlfriends was relatively low. Lifetime injection drug use (IDU) was reported by 4.1% of the total sample and was associated with recent urban residence, CSW patronage, and sexual precocity. Findings suggest gaps in Thailand's condom campaign and the need to better address HIV risk associated with having multiple partners.

As part of routine surveillance, an HIV-1 serosurvey of 366,074 members of successive cohorts of young Thai men entering service with the Royal Thai Army (RTA) was conducted between November 1989 and November 1995. We analyzed regional and temporal trends in HIV-1 seroprevalence in young men in Thailand and determined the proportion of infections resulting from subtypes E and B in this population in 1992 and 1995. The prevalence in 1992 was compared with that in 1995 by region and demographic group. The HIV-1 subtype was determined in a random sample of HIV-1-positive specimens in 1992 and 1995 using a V3 peptide enzyme immunoassay. From a peak of 3.7% in 1993, overall seroprevalence declined to 3.0% in 1994 and further in 1995 to 2.5%. Between 1992 and 1995, the absolute decrease in seroprevalence was greatest in the upper North (from 12.5% to 5.3%), where the prevalence has been the highest. Overall, 96.9% and 95.9% of typable specimens were determined to be subtype E in 1992 and 1995, respectively. Decline in HIV-1 seroprevalence among young men in Thailand has continued, which suggests that HIV control programs in Thailand may have been successful in decreasing spread of HIV-1. Almost all HIV-1 infections resulted from subtype E.

Data from recruitment and screening for a phase I/II preventive HIV-1 vaccine trial in Thailand were evaluated with respect to correlates of participation at each phase. Correlates included demographic variables, motivation for interest in the trial, and factors related to communication and contact. Participants were recruited at two sites through varied methods. The majority of prescreenees reported altruistic motives for interest in the trial and blood donors emerged as a group that may have been particularly altruistic. Findings indicated site differences in attrition during recruitment and screening, but not in enrollment into the vaccine trial. Blood donation and willingness to be contacted by phone at home were significantly related to making and keeping screening appointments.

Geographic and demographic correlates of risk for HIV-1 seropositivity were studied in 120,216 young men selected by lottery for service in the Royal Thai Army (RTA). The study population consisted of men selected between November 1991 and May 1993. Venous blood was collected at induction, and a brief demographic questionnaire was administered. HIV-1 seropositivity was established by Western blot confirmation of duplicate reactive ELISAs. Geographic variable provided the strongest correlate of risk, clearly distinguishing residents of the upper north, Bangkok, and the central region from the northeast. Overall 12.2% of men from the upper north were HIV-positive. Men who had lived in rural areas were at less risk in most regions of the country, but had equal risk in the upper north. Unmarried men and those with less education were at higher risk throughout the country. These data provide valuable information on the prevalence of HIV infection in one segment of the general population. Continued surveillance of this group will facilitate evaluation of Thailand's response to the epidemic.

OBJECTIVE:To evaluate trends in HIV-1 seroprevalence in Thailand.DESIGN:HIV-1 serosurvey of successive cohorts of young Thai men entering service with the Royal Thai Army (RTA) between November 1989 and November 1994.METHODS:In November 1989, the RTA Medical Department began routine HIV-1-antibody screening of men who were selected by lottery for conscription. Between November 1989 and November 1994, 311,108 young men were screened at induction. Demographic data were collected between November 1991 and May 1993 and again in November 1994.RESULTS:The seroprevalence of HIV-1 among conscripts nationwide increased rapidly from 0.5% in 1989 to 3.5% in 1992 and reached 3.7% in 1993. In 1994, the overall prevalence decreased to 3.0%. The decrease was greatest in the upper North (from 12.4% in 1992 to 7.9% in 1994), where the prevalence has been the highest. However, decreases were observed in men from all regions of residence in the country, from both rural and urban areas, and at all educational levels.CONCLUSIONS:The decline in prevalence suggests declining incidence and that HIV control programs in Thailand are having an impact on the HIV epidemic.

Multiple genetic subtypes of human immunodeficiency virus type 1 (HIV-1) have been identified among internationally collected isolates. The HIV-1 epidemic in Thailand is largely due to B and E subtypes of virus. Dual infection with distinct HIV-1 subtypes would suggest that antiviral immunity evoked by one subtype can be incompletely protective against a second. Polymerase chain reaction typing and serologic typing were used to screen a panel of specimens from HIV-1-infected subjects in Thailand. Two persons simultaneously harbored HIV-1 of env subtypes B and E, and this was confirmed by colony hybridization with subtype-specific probes and nucleotide sequence analysis of a 630-bp fragment of gp120 from multiple molecular clones. In addition, both subtypes were identified in cocultured peripheral blood mononuclear cells from 1 individual. These data provide the first evidence of dual HIV-1 infection in humans and reinforce the need for polyvalent vaccines.

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2. N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/m3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early-and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late-stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early-or late-stage patients.

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2. N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/m3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early-and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late-stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early-or late-stage patients.

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2, N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/mm3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early- and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late-stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early- or late-stage patients.