Chantapong Wasi

The epidemiology of HIV infection and AIDS in Thailand.

There were very few AIDS cases reported in Thailand as of 1988, where HIV was introduced relatively late in the course of the AIDS pandemic. Thailand was therefore classified as an epidemiologic pattern III country with regard to the HIV/AIDS pandemic. Also in 1988, however, Thailand experienced a major and rapid increase in HIV prevalence among IV drug users (IVDU). The Thai experience with HIV after the rapid spread first among IVDUs has been successive waves of HIV transmission to female prostitutes, then to their non-IVDU male clients, and then into the non-prostitute wives and girlfriends of these latter men in the general population. Three years after being declared a pattern III country, 300,000 people in Thailand were estimated to be infected out of a population of 55 million. Reasons for this unprecedented rapid spread of HIV infection may eventually come from research on sexual behavior and related diseases given the lack of evidence for human host genetic factors or particularly virulent etiologic agent factors to explain the phenomenon. The reason and dynamics behind the timing and rapidity of the 1988 epidemic among IVDUs for now remains unknown. The authors note that the scenario of HIV transmission observed in Thailand also seems to be unfolding in neighboring countries. HIV infection among female prostitutes and heterosexual men is consistently highest in the northern Thai provinces adjacent to Myanmar and Laos. This paper reviews the epidemiology and prevention of HIV infection and AIDS in Thailand, updating previous reports and commentary, and including previously unpublished or not widely available data.

Continued high HIV-1 incidence in a vaccine trial preparatory cohort of injection drug users in Bangkok, Thailand

Background A large epidemic of HIV-1 subtype B began among injection drug users (IDUs) in Bangkok in 1988. Despite ongoing prevention efforts, HIV-1 prevalence among IDUs remained at 30–50% through the 1990s. ObjectivesTo measure the incidence of HIV-1 infection and related risk factors to guide prevention efforts and to evaluate the feasibility of conducting an HIV vaccine efficacy trial. Design and methodsA prospective cohort study in which IDUs attending methadone treatment programs in Bangkok were screened during 1995–1996 for enrollment into the study. IDUs found to be HIV-seronegative on two occasions were offered enrollment with follow-up visits every 4 months. On each visit participants were evaluated with a questionnaire and serologic testing. ResultsA total of 1209 HIV-negative IDUs were enrolled. Through the end of 1998, the overall HIV-1 incidence rate was 5.8 (95% confidence interval, 4.8–6.8) per 100 person–years of follow-up. HIV-1 subtypes E and B accounted for 79 and 21% of infections, respectively. On multivariate analysis, HIV-1 seroconversion was primarily associated with the frequency of heroin injection, the sharing of injection equipment, and incarceration, especially with drug injection. Sexual behavior was not associated with increased risk for HIV-1. Risk factors for infection with HIV-1 subtypes E and B were similar. ConclusionHIV-1 transmission risk remains high among Bangkok IDUs despite methadone treatment and other current prevention strategies. There is an urgent need to address this ongoing epidemic, especially in jails and prisons. This study led to the initiation in 1999 of a phase III HIV-1 vaccine efficacy trial in this population.

Determination of HIV-1 subtypes in injecting drug users in Bangkok, Thailand, using peptide-binding enzyme immunoassay and heteroduplex mobility assay : evidence of increasing infection with HIV-1 subtype E

ObjectivesTo evaluate the sensitivity, and specificity of peptide-binding enzyme immunoassay (PEIA), and heteroduplex mobility assay (HMA) for the determination of HIV-1 subtypes B, and E; to determine the proportions of infections due to subtypes B, and E over time;, and to generate data on DNA sequences of the C2-V3 region of the env genes. MethodsHIV-1 subtyping was conducted by PEIA, and HMA on blood specimens obtained from 97 injecting drug users (IDU) infected with HIV between 1988, and 1993. Genetic sequencing was performed on 84 specimens. ResultsBoth laboratory methods were highly sensitive, and specific for the determination of HIV-1 subtypes B, and E. The two tests were complementary; samples which could not be typed by HMA were correctly typed by PEIA, and vice versa. While subtype B accounted for 80.4% (78 out of 97) of infections overall, the proportion of new infections due to subtype E increased from 2.6% (one out of 38) in 1988–1989 to 25.6% (11 out of 43) in 1990–1991, and to 43.8% (seven out of 16) in 1992–1993 (4cH2 for linear trend, P< 0.001). ConclusionsHMA, and PEIA are practical, sensitive, and specific laboratory methods for the determination of HIV-1 subtypes in Thailand, and may be useful in other geographic areas to define the molecular epidemiology of the global HIV-1 pandemic. Data suggest that the proportion subtype E infections have increased among Bangkok IDU from 1988 through 1993.

Viral load differences in early infection with two HIV-1 subtypes.

ObjectivesInformation on early HIV-1 infection has come primarily from studies of persons infected with subtype B in North America and Europe; much less is known about other subtypes. The purpose of the present study was to compare the virologic and immunologic parameters following seroconversion among recently-infected persons infected with either of two different HIV-1 subtypes. MethodA prospective cohort study was carried out at methadone treatment clinics administered by the Bangkok Metropolitan Administration, Thailand. A total of 130 HIV-1-infected seroconverters (103 with HIV-1 subtype E and 27 with subtype B) were included in the study. The main outcome measures were serial HIV-1 RNA viral load, natural killer cell percentage, CD4 and CD8 lymphocyte counts since seroconversion. ResultsThe demographic and behavioral characteristics of persons with either subtype were similar. Median RNA viral levels at the earliest time within 3 months of seroconversion were more than three times higher for persons infected with subtype E than subtype B (63 100 versus 18 050 copies/ml, P = 0.001). However, this difference decreased over time such that viral loads were similar at 12, 18, and 24 months following seroconversion. The CD4 and CD8 lymphocyte counts were similar in infections with either subtype during the entire period up to 24 months post-seroconversion. ConclusionsHigher viral loads associated with subtype E may result from inter-subtype biological differences; however, the epidemiological dynamics of transmission in Bangkok may have also contributed to this phenomenon.

WHY DO HIV-1 SUBTYPES SEGREGATE AMONG PERSONS WITH DIFFERENT RISK BEHAVIORS IN SOUTH AFRICA AND THAILAND ?

Initial research on the genetic variability of human immunodeficiency virus (HIV)-1 has indicated that HIV-1 envelope subtype B is dominant in Western countries where homosexuality and injecting drug use are the major risk factors, while env subtypes A, C, D, and E predominate in Africa and Asia where most transmission is heterosexual. Data from South Africa and Thailand suggest that, due to limited mixing of population subgroups, largely independent HIV epidemics caused by different genotypic subgroups may co-exist in a given geographic area. On the other hand, the possibility that HIV-1 subtypes differ in transmission efficiency by exposure mode also has some support. For example, subtypes E and C appear to be better adapted to penile-vaginal transmission, while subtypes B, E, and C may be transmitted efficiently through blood. Factors such as sexual mixing patterns (e.g., commercial sex work) and the prevalence of sexually transmitted diseases must also be considered when examining HIV-1 subtype transmission differences. The use of new assays that allow for the accurate measurement of viral levels in plasma, semen, and genital secretions should complement epidemiologic estimates of transmission efficiency for various HIV-1 subtypes.

Genetic Similarity of HIV Type 1 Subtype E in a Recent Outbreak among Injecting Drug Users in Northern Vietnam to Strains in Guangxi Province of Southern China

To investigate the molecular epidemiology of a recent HIV-1 outbreak in northern Vietnam and its relation to the epidemic in surrounding areas, we analyzed 17 HIV-positive blood specimens from 3 heterosexuals, 2 sexually transmitted disease patients, and 12 injecting drug users (IDUs), collected in 4 provinces near Hanoi in 1998. These were compared with the specimens from Ho Chi Minh City (n = 10) and An Giang Province (n = 10) in southern Vietnam and with published sequences from neighboring countries. Genetic subtyping based on the env C2/V3 sequences revealed that HIV-1 subtype E predominated throughout Vietnam in all risk populations; the exception was one typical United States-European-type HIV-1 subtype B detected in a patient in Ho Chi Minh City, the first case of HIV infection identified in Vietnam in 1990. The HIV-1 subtype E sequences identified in 9 of the 12 IDUs from northern provinces were closely related phylogenetically to those in IDUs in nearby Guangxi Province of China, and also shared a common amino acid signature downstream of the env V3 loop region. The low interperson nucleotide diversity among IDUs in northern Vietnam supports the view that HIV-1 subtype E was introduced recently among IDUs in northern Vietnam. These data indicate a linkage between HIV-1 circulating among IDUs in northern Vietnam and southern China, and suggest recent transborder introductions as the likely source of HIV-1 subtype E in northern Vietnam.

Was the 1988 HIV epidemic among Bangkok's injecting drug users a common source outbreak?

Objective:To describe and understand the genesis of the explosive 1988 HIV epidemic among Thai injecting drug users (IDU) in Bangkok. Design:Two cross-sectional HIV seroprevalence sample surveys (SP-1 and SP-2) of drug users, including IDU at various stages of treatment. SP-1, a 10-week estimate of prevalence, was conducted by the Bangkok Metropolitan Administration (BMA) in their detoxification clinics from 5 January to 7 March 1988. SP-2 estimated prevalence in 1 week, 12–15 September 1988, in the same 18 BMA clinics. Both surveys included an administered questionnaire that gathered demographic and behavioral information. Methods:Analysis of HIV prevalence by clinic in both SP-1 and SP-2, and the relationships between demographic data, behavioral variables, arrest history and HIV positivity in SP-1. Results:Data from individual clinics in SP-1 show significant increases in HIV prevalence among IDU sampled from early February 1988. Of IDU sampled in five ‘early’ clinics before 9 February, 2% were positive; in the 13 ‘late’ clinics sampled from 9 February until 7 March, 27% were positive. By September 1988, however, the early and late clinics were no longer heterogenous for HIV prevalence. For current IDU, HIV-positivity was associated with the sharing of injection equipment in SP-1 [odds ratio (OR), 1.82; 95% confidence limits (CL), 1.31–2.53] and recent jail or prison stay (OR, 2.15; 95% CL, 1.18–3.98). Conclusions:The behavioral factors associated with the HIV epidemic among Bangkoks IDU are similar to those described elsewhere. The monthly incidence of 5% from February to September 1988 suggests extensive needle or injection equipment sharing networks among IDU in Bangkok. Additionally, the pattern of HIV-positivity by detoxification clinic over time in early 1988, and then in September 1988 is consistent with a relationship to the prison amnesty of early December 1987. Shortly after that date, an undisclosed number of former IDU, a substantial number of whom were still injecting, and may have become HIV-positive while in custody, returned to resume injecting within existing drug-using networks throughout Bangkok and elsewhere in Thailand.

AIDSVAX (MN) in Bangkok injecting drug users: a report on safety and immunogenicity, including macrophage-tropic virus neutralization.

A randomized, double-blind, placebo-controlled phase I/II study of AIDSVAX (MN) was conducted among injecting drug users in Bangkok, Thailand. Four doses of vaccine (300 microg of MN-rgp120 in alum) or placebo (alum) were given at study entry and at 1, 6, and 12 months. The objectives of the study were to evaluate (1) the feasibility of conducting vaccine trials in this population; (2) the safety of this candidate AIDS vaccine; and (3) the immunogenicity of this vaccine. Thirty-three volunteers (22 vaccine and 11 placebo recipients) were recruited. None were lost to follow-up during the 18-month study. Mild reactogenicity was noted, which was similar in both vaccine and placebo recipients. The vaccine induced anti-HIV-1 antibody in all vaccine recipients. Maximal titers of binding antibodies of MN-rgp120 and the V3 domain of MN-rgp120 were induced after the third (6 month) dose while maximal neutralizing antibodies followed the fourth (12 month) dose. The vaccine-induced antibodies from several volunteers were capable of neutralizing macrophage-tropic, subtype B viruses (301660 and JRCSF) detected in a PBMC-based assay. Binding and neutralizing antibodies declined about 10-fold in the 6 months after the last boost. Two vaccinees became infected during the trial, both with subtype E viruses. A phase III efficacy trial, using a bivalent gp120 vaccine containing antigens from a subtype B virus (MN) and a subtype E virus (A244), was initiated in March 1999 in injecting drug users in Bangkok.

Primary Infection of Human Herpesvirus 6 in Children with Vertical Infection of Human Immunodeficiency Virus Type 1

The role of human herpesvirus 6 (HHV-6) infection in 227 children born to human immunodeficiency virus (HIV)-seropositive mothers was investigated. Of 41 HIV-uninfected infants, 3 (7%) were positive for HHV-6 DNA in the first month of life, suggesting possible intrauterine infection. The cumulative infection rates of HHV-6 at 6 and 12 months of age were significantly lower in HIV-infected children (11% and 33%, respectively) than in uninfected children (28% and 78%, respectively; P<.001). There was an association between high CD4+ cell numbers (>15%) before HHV-6 infection and high HHV-6 infection rate. Twenty-two infants with HIV classed as Centers for Disease Control and Prevention stages N1 or N2 were studied for an association of HHV-6 infection with progression of HIV disease. Ten of the infants had HHV-6, and 12 did not. In 5 of the infants without HHV-6 (42%), HIV disease had not progressed by 1 year of age; however, HIV disease had progressed in all 10 children with HHV-6 infection. These results suggest an association of HHV-6 infection and progression of HIV disease in the study children with vertical HIV-1 infection (P<.05).

A simplified and economical intradermal regimen of purified chick embryo cell rabies vaccine for postexposure prophylaxis

Healthy volunteers were randomized to receive either intradermal purified chick embryo cell rabies vaccine (PCEC) alone (0.1 ml at each of two sites on days 0, 3 and 7, and at one site on days 28 and 90) (n = 81), or intradermal PCEC with one dose of human rabies immunoglobulin (HRIG) intramuscularly at 20 IU kg-1 on day 0 (n = 52). Neutralizing antibody (NAB) was detectable in every volunteer, in both groups, from day 14 up to day 365. The peak NAB occurred on day 28 in both groups. No significant suppressive effects of HRIG on NAB response were observed. Side-effects were mild and self-limiting. These preliminary results suggest that this simplified low-dose intradermal regimen could be an alternative schedule in rabies postexposure prophylaxis, resulting in lower overall costs.