Why do HIV-1 subtypes segregate among persons with different risk behaviors in South Africa and Thailand?

PIP: 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.^ieng

Explosive spread and effective control of human immunodeficiency virus in northernmost Thailand: the epidemic in Chiang Rai province, 1988-99.

The human immunodeficiency virus type 1 (HIV-1) epidemic began in Asia later than most in other regions but then spread very rapidly. Upper northern Thailand was severely affected, with among the highest infection rates in Asia. The first 12 years of the HIV epidemic in Chiang Rai, Thailand's northernmost province are described. HIV infection was not reported in Chiang Rai until 1988 but, within a few years more than half of the brothel-based female sex workers and one in six of 21-year-old male Royal Thai Army conscripts from the province were HIV infected. Infection rates in Chiang Rai have since declined following an aggressive prevention campaign, but the number of AIDS cases continues to mount, along with profound demographic, social and economic effects.

Estimated rate of HIV-1-infectious but seronegative blood donations in Bangkok, Thailand.

OBJECTIVES: To determine HIV seroprevalence and incidence among various blood donor types, and to estimate the rate of window-period blood donations. DESIGN: Retrospective cohort from computerized donor records. METHODS: Records were analysed from all 60,483 donors (contributing 97,464 donor units) at a public university teaching hospital blood bank in Bangkok, Thailand, from 1 January 1990 to 30 June 1993. Annual HIV incidence among 14,482 repeat donors who were HIV-seronegative on their first donation was calculated assuming equal probability of seroconversion between last seronegative and first seropositive donations. To estimate the probability of window-period donations, we assumed that the time from HIV infectivity to onset of detectable antibody was 45 days. RESULTS: In 1990, HIV incidence calculated for all repeat donors was 307 per 100,000 person-years; the probability of a window-period donation was 38 in 100,000 donations or one in 2644 donations. During 1991-1993, this probability decreased by one-half. However, one-time donors were more than twice as likely as repeat donors to be HIV-1-seropositive. CONCLUSIONS: The rate of HIV window-period blood donations among Thai repeat donors was relatively high compared with that in developed countries and was probably even higher among one-time donors. Improved donor deferral criteria are needed in Thailand.

PIP: In countries with a high incidence of human immunodeficiency virus (HIV), blood donations made during the "window period" (time between infection and the development of detectable antibody) pose a serious risk. To assess the extent of this risk in Thailand, records of all 60,483 blood donors at Bangkok's Mahidol University from January 1, 1990, to June 30, 1993, were reviewed. A retrospective cohort of 14,482 repeat donors was created by identifying those who were HIV-negative at their first screening and made one or more subsequent donations (mean, 3.6). Among these repeat donors, 40 (0.3%) seroconverted during the study period. The time from HIV infectivity to onset of detectable antibody was assumed to be 45 days. The HIV transmission rate among repeat donors resulting from donations during the window period was estimated to be 1 in 2644 units transfused in 1990 and 1 in 5000 units transfused during 1991-93. Extrapolation of these estimates suggests that, during the 1991-93 period, 57 units in Bangkok (194 units nationwide) were from donors in the HIV window period. Voluntary 1-time donors were 1.9 times more likely to be HIV-infected than voluntary repeat donors, while paid one-time donors were 13.7 times more likely to be seropositive than paid repeat donors. In 1994, the hospital initiated HIV p24 antigen screening of all donated blood; although this technique shortens the window period and should improve blood safety, improved donor referral criteria are needed.

HIV-1 infection in young men in northern Thailand.

OBJECTIVES: To determine risk factors for HIV-1 infection in young men in northern Thailand. METHODS: At enrollment into a prospective study, data were collected from a self-administered questionnaire and serologic testing on a cohort of 1115 young men selected by lottery for conscription. RESULTS: The overall HIV-1 infection rate was 6.9%; however, the rate was 15.3% among the 387 (34.7%) men who had been living in the upper north subregion of Thailand compared with 2.5% for the remaining 728 men (P < 0.001). A history of sex with female prostitutes was reported by 74.7% of men and increased frequency of this type of sex was highly associated with HIV-1 infection and a history of sexually transmitted disease (STD) symptoms (chi 2 for trend, P < 0.001). In stratified and multivariate analyses, however, history of STD symptoms, reported by 42.5% of the cohort, was most strongly associated with HIV-1 infection. Only 42.8% of men who reported sex with prostitutes had used condoms more than half the time. CONCLUSIONS: Young men in the general population in northern Thailand are at high risk for HIV-1 infection via sex with female prostitutes; STD are highly associated with HIV-1 infection. Increasing condom use and controlling STD should be immediate goals of HIV control programs.

PIP: This study sought to determine risk factors for HIV-1 infection in young men in northern Thailand. This cohort of 1115 young men were selected by lottery for conscription and at enrollment into this prospective study, data were collected from a self-administered questionnaire and serologic testing. The overall HIV-1 infection rate was 6.9%; however, the rate was 15.3% among the 387 (34.7%) men who had been living in the upper north subregion of Thailand compared with 2.5% for the remaining 728 men (p 0.001). A history of sex with female prostitutes was reported by 74.7% of men and increased frequency of this type of sex was highly associated with HIV-1 infection and a history of sexually transmitted disease (STD) symptoms (chi square for trend, p 0.001). In stratified and multivariate analyses, however, history of STD symptoms, reported by 42.5% of the cohort, was most strongly associated with HIV-1 infection. Only 42.8% of men who reported sex with prostitutes had used condoms more than half the time. Young men in the general populations in northern Thailand are at high risk for HIV-2 infection via sex with female prostitutes; STDs are highly associated with HIV-2 infection. Increasing condom use and controlling STD should be immediate goals of HIV control programs.

Implementing short-course zidovudine to reduce mother-infant HIV transmission in a large pilot program in Thailand.

OBJECTIVES: To describe a pilot mother-infant HIV prevention program started by the Ministry of Public Health of Thailand in July 1998 and to report on the first year of its implementation. DESIGN: Analysis of monthly summaries of data from project logbooks, simple data forms in antenatal clinics and delivery rooms, site visits and workshops, mail survey. SETTING: All 89 public hospitals in seven north-eastern provinces of Thailand. PARTICIPANTS: Childbearing women, program officials. INTERVENTIONS: Counseling and HIV testing for pregnant women, short-course antenatal zidovudine for HIV-infected pregnant women, and infant formula for their children. MAIN OUTCOME MEASURES: Proportion of women with HIV test, proportion of HIV-infected women receiving zidovudine. RESULTS: Of 75,308 women who gave birth between July 1998 and June 1999, 74,511 (98.9%) had antenatal care, 51,492 (69.1%) in the same district and 23,019 (30.9%) outside the district where they gave birth. HIV test results were available at delivery for 46,648 (61.9%) women, 410 (0.9%) of whom tested positive. Of these HIV-infected women, 259 (63.2%) participated in the zidovudine program and 6 (1.5%) received zidovudine from other sources. The proportion of women whose HIV test results were known and proportion of HIV-infected women who received zidovudine increased significantly during the year. CONCLUSIONS: A mother-infant HIV prevention program using short-course antenatal zidovudine was quickly implemented in a large region of Thailand with moderate HIV prevalence. This successful experience is leading to national implementation of a perinatal HIV prevention program in Thailand and may prompt other developing countries to start similar programs.

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.

OBJECTIVES: To 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. METHODS: HIV-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. RESULTS: Both 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 (chi 2 for linear trend, P < 0.001). CONCLUSIONS: HMA 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.

The evolving molecular epidemiology of HIV-1 envelope subtypes in injecting drug users in Bangkok, Thailand: implications for HIV vaccine trials.

OBJECTIVE: To genetically characterize HIV-1 strains in injecting drug users (IDU) in Bangkok, Thailand in 1994, and compare these with strains found earlier in Thai IDU; such information is essential for HIV-1 vaccine development and evaluation. METHODS: Peripheral blood mononuclear cells were collected from 84 IDU attending 14 drug treatment clinics in Bangkok in 1994. DNA was amplified using a nested polymerase chain reaction (PCR) procedure and sequenced directly (without cloning) from the PCR products. The V3 and flanking regions (345 nucleotides) of the env gene were analyzed using a neighbor-joining tree. RESULTS: Only one (1%) strain was a typical subtype B virus, 69 (82%) were genetically distinct subtype B' viruses (Thai B), and 14 (17%) were subtype E strains (Thai A). Persons with recently acquired infection were more likely to have subtype E viruses (P < 0.001) than those in our 1991 survey, who were more likely to have subtype B' viruses. Pairwise intra-subtype differences within subtypes E and B' were 5.3 and 4.3%, respectively, compared with 3.4 and 3.5% among strains collected in 1991 in Thailand. CONCLUSION: The genetic diversity within subtypes B' and E in Thailand and the proportion of new infections due to subtype E viruses among Bangkok IDU are increasing significantly. These data highlight the importance of monitoring the molecular epidemiology of HIV-1 in populations being considered for HIV-1 vaccine trials.

Rapid increase in HIV-related tuberculosis, Chiang Rai, Thailand, 1990-1994.

OBJECTIVE: Chiang Rai, the northernmost province of Thailand, has experienced an explosive HIV epidemic since 1989. This study assessed the impact of HIV infection on tuberculosis (TB) in the area. METHODS: We analyzed the incidence of reported TB in the province from 1982 through 1993 and TB registry data at Chiang Rai Hospital from 1985 through 1994. RESULTS: Following a steady decline in reported TB from 1982 through 1991, the incidence of TB increased sharply after 1991. TB registry data from Chiang Rai Hospital, which began confidential HIV testing in October 1989, indicated a steady and rapid increase in the number and proportion of HIV-seropositive TB patients from four (1.5% of all TB patients) in 1990 to 207 (45.5%) in 1994 (P < 0.001). Compared with HIV-negative TB patients, HIV-positive TB patients were more likely to be men, aged 20-39 years and have extrapulmonary TB (P < 0.001). Treatment completion rates were similar. Twelve months after beginning TB treatment, HIV-positive TB patients had a mortality rate of 68.6% [95% confidence interval (Cl), 62.7-74.3] compared with 10.0% (95% Cl, 8.3-12.1%) in HIV-negative patients (P < 0.001). CONCLUSION: Thailand and other Asian countries where HIV is spreading rapidly must promptly address the dual epidemic of TB and HIV in order to reduce preventable morbidity and mortality.

Clinical disease associated with HIV-1 subtype B' and E infection among 2104 patients in Thailand.

BACKGROUND: Two HIV-1 envelope subtypes have accounted for virtually all infections in Thailand: subtype B' (Thai B), found mainly in injection drug users (IDU), and subtype E, found in over 90% of sexually infected persons and an increasing proportion of IDU in recent years. It remains unclear whether there are differences in pathogenesis associated with these HIV-1 subtypes. METHODS: From November 1993 to June 1996, demographic, risk, clinical, and laboratory data were collected by enhanced surveillance from HIV-infected inpatients (> or =14 years) at an infectious disease hospital near Bangkok. HIV-1 subtype was determined by V3-loop peptide enzyme immunoassay (EIA). Because of confounding, multivariate analyses were stratified by risk category and controlled for sex and age. RESULTS: The infecting HIV-1 subtype was determined for 2104 (94.9%) of 2217 HIV-infected patients with complete data: 284 (13.5%) were subtype B', 1820 (86.5%) were E. Specimens from 113 (5.1%) patients were non-reactive or dually reactive on peptide EIA and were excluded. Among IDU, 199 (67.2%) had subtype B', and 97 (32.7%) had E. IDU accounted for 70.1% (199/284) of patients with subtype B' and 5.3% (97/1820) of those with E. Patients infected with HIV-1 subtypes B' or E had similar spectrums of opportunistic infections (OI), levels of immunosuppression, and in-hospital mortality rates. Of patients who did not inject drugs, more patients infected with subtype E had extrapulmonary cryptococcosis than those with subtype B' (adjusted odds ratio, 2.6; 95% confidence interval, 1.28-5.37). CONCLUSION: HIV-1 subtypes B' and E seem to be associated with similar degrees of immunosuppression and, with one exception, with similar OI patterns. These data do not suggest an association between HIV-1 subtype and differences in pathogenicity.

HIV-1 seroprevalence among childbearing women in northern Thailand: monitoring a rapidly evolving epidemic.

OBJECTIVES: To describe trends in prevalence of HIV-1 infection among women giving birth at Chiang Rai Hospital (CRH) and to assess risk factors associated with HIV infection in this population. DESIGN: Analysis of hospital registry data for all deliveries at CRH from 1990 to mid-1997. METHODS: From 1990 to mid-1997, women giving birth at CRH were tested for HIV-1 infection using enzyme immunoassay (EIA); positive sera were confirmed using a different manufacturer's EIA. Demographic and clinical data were abstracted from delivery-ward log books. RESULTS: Data from 40723 deliveries indicated that overall HIV-1 seroprevalence increased sharply, from 1.3% in 1990 to a peak of 6.4% in 1994, and then declined to 4.6% in the first 6 months of 1997. Prevalence was highest, at 7.0%, among young (age < or = 24 years) primigravidas, compared with 2.4% among older (age > or = 25 years) multigravidas. When we controlled for age, prevalence declined 40% from 1994 to 1997 among young primigravidas (95% confidence interval for percentage reduction, 16-57). Amongst older multigravid women, prevalence was consistently lower but increased steadily from 2.7% in 1994 to 3.4% in 1997. CONCLUSIONS: A rapid rise in HIV prevalence in childbearing women was followed by a sharp decline among young primigravidas. In each year, the prevalence was highest among young primigravidas. They may be the best subgroup of pregnant women for monitoring HIV epidemic trends, but they also represent a challenging prevention priority that will require its own targeted interventions.

Mucosal disruption due to use of a widely-distributed commercial vaginal product: potential to facilitate HIV transmission.

OBJECTIVE: Policresulen vaginal suppositories are a condensation product of metacresolsulfonic acid and formaldehyde. We investigated their use by female commercial sex workers (CSW) and whether such use could facilitate HIV transmission. METHODS: We interviewed female CSW in Thailand about use of the product, and we directly observed the effects of self-administration of a single suppository by each of six women. RESULTS: Of 200 CSW interviewed, 32% had used policresulen vaginal suppositories in the preceding year and 46% had used them at some time. Many used them for reasons not listed on the package insert, such as improving their male partners' sexual pleasure, and most did not abstain from vaginal sex following use. Among 36 brothel-based and 67 non-brothel-based CSW with known HIV infection, the use of the product was not associated with HIV-1 infection (adjusted relative risk 1.0, 95% confidence interval, 0.5-2.0). Exfoliation of the vaginal and cervical mucosa was observed in all six CSW 1 day after product use, and, although it could have been the result of repeated examinations, an increase in genital HIV-1 RNA shedding was also detected in all three HIV-seropositive women. CONCLUSION: Although there was no epidemiological association with HIV infection, policresulen vaginal suppository use did disrupt the genital mucosa and therefore may have the potential to facilitate HIV transmission. Drug licensing authorities may wish to reassess the safety of this product. If the product continues to be distributed, steps should be taken to limit its use to the specific conditions for which it is indicated and to ensure that women abstain from vaginal sex following its use.

HIV-1 seroconversion in a prospective study of female sex workers in northern Thailand: continued high incidence among brothel-based women.

OBJECTIVES: To determine the incidence of HIV-1 infection, temporal trends in incidence, and risk factors for seroconversion in a cohort of female commercial sex workers (CSW) in upper northern Thailand, the region of Thailand with the highest rates of HIV-1 infection. METHODS: CSW were enrolled from 1991 through 1994 and evaluated prospectively with interviews, physical examination, testing for sexually transmitted diseases (STD), and serologic testing for HIV-1 infection. RESULTS: The incidence of HIV-1 seroconversion in the first year of follow-up was 20.3 per 100 person-years among 126 brothel-based CSW and 0.7 per 100 person-years among 159 other CSW who worked in other venues such as bars or massage parlors. Incidence remained elevated among brothel-based CSW who were enrolled later in the study compared with those who enrolled earlier. Through 1996, 30 women seroconverted. In a multivariable proportional hazards model, seroconversion was significantly associated (P < 0.05) with brothel-based sex work (adjusted risk ratio, 7.3) and Chlamydia trachomatis cervical infection (adjusted risk ratio, 3.3). CONCLUSION: Despite national HIV control efforts and declining rates of infection among young men in Thailand, brothel-based CSW may continue to be at high risk for HIV-1 infection. Additional efforts are needed to provide alternative economic choices for young women, to ensure universal condom use during commercial sex, and to develop new prevention technologies.

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

OBJECTIVES: Information 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. METHOD: A 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. RESULTS: The 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. CONCLUSIONS: Higher 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.

Oral zidovudine during labor to prevent perinatal HIV transmission, Bangkok: tolerance and zidovudine concentration in cord blood. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVES: To evaluate tolerance for the oral administration of zidovudine (ZDV) during labor and measure the resulting ZDV concentrations in umbilical cord blood. DESIGN: A cross-sectional study of women in a placebo-controlled trial of short-course ZDV (twice a day from 36 weeks' gestation until labor and every 3 h during labor) to prevent perinatal HIV transmission in Bangkok. METHODS: Umbilical cord blood was collected. Sixty control specimens and specimens from 372 women (182 in the ZDV group, 190 in the placebo group) were tested for ZDV by radioimmunoassay (lower detection limit < 1 ng/ml). RESULTS: All women in the ZDV group took one or more labor dose, 170 (93%) took their last dose within 3 h of delivery, and only five (3%) experienced nausea or vomiting, a proportion similar to the placebo group. The median concentration of ZDV in the cord blood in the ZDV group was 252 ng/ml (range, < 1-1133 ng/ml); 31 (17%) specimens were less than 130 ng/ml (0.5 microM), the concentration thought to be active against HIV in vitro. Median concentrations were 189 ng/ml in specimens from women taking one or two labor doses, 290 ng/ml in those taking three or four doses, and 293 ng/ml in those taking more than four doses (P < 0.01). The ZDV concentration was not associated with time since the last dose, body weight, or perinatal transmission. CONCLUSION: Oral intrapartum ZDV was feasible and well tolerated. Most ZDV concentrations in the cord blood after oral dosing during labor were at therapeutic concentrations but were lower than those reported after continuous intravenous administration. Although concentrations were not associated with perinatal transmission, these data do not exclude the possibility that intrapartum and neonatal chemoprophylaxis is effective.

Maternal viral load and timing of mother-to-child HIV transmission, Bangkok, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVES: To determine the proportion of HIV-1-infected infants infected in utero and intrapartum, the relationship between transmission risk factors and time of transmission, and the population-attributable fractions for maternal viral load. DESIGN: Prospective cohort study of 218 formula-fed infants of HIV-1-infected untreated mothers with known infection outcome and a birth HIV-1-positive DNA PCR test result. METHODS: Transmission in utero was presumed to have occurred if the birth sample (within 72 h of birth) was HIV-1-positive by PCR; intrapartum transmission was presumed if the birth sample tested negative and a later sample was HIV-1-positive. Two comparisons were carried out for selected risk factors for mother-to-child transmission: infants infected in utero versus all infants with a HIV-1-negative birth PCR test result, and infants infected intrapartum versus uninfected infants. RESULTS: Of 49 infected infants with an HIV-1 birth PCR result, 12 (24.5%) [95% confidence interval (CI), 14 -38] were presumed to have been infected in utero and 37 (75.5%) were presumed to have been infected intrapartum. The estimated absolute overall transmission rate was 22.5%; this comprised 5.5% (95% CI, 3-9) in utero transmission and 18% (95% CI, 13-24) intrapartum transmission. Intrapartum transmission accounted for 75.5% of infections. High maternal HIV-1 viral load (> median) was a strong risk factor for both in utero [adjusted odds ratio (AOR) 5.8 (95% CI, 1.4-38.8] and intrapartum transmission (AOR, 4.4; 95% CI, 1.9-11.2). Low birth-weight was associated with in utero transmission, whereas low maternal natural killer cell and CD4(+) T-lymphocyte percentages were associated with intrapartum transmission. The population-attributable fraction for intrapartum transmission associated with viral load > 10 000 copies/ml was 69%. CONCLUSIONS: Our results provide further evidence that most perinatal HIV-1 transmission occurs during labor and delivery, and that risk factors may differ according to time of transmission. Interventions to reduce maternal viral load should be effective in reducing both in utero and intrapartum transmission.

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. OBJECTIVES: To 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 METHODS: A 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. RESULTS: A 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. CONCLUSION: HIV-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.

Sequence analysis of an HIV type 1 env subtype E isolate from Thailand with discordant V3-loop serotyping.

PIP: HIV-1 genetic subtypes B and E are currently circulating in Thailand. Subtype E accounts for more than 90% of heterosexual transmission nationwide, while subtype B is transmitted mainly among IV drug users. This paper reports an HIV-1 Thai E isolate which yielded discordant results in serotyping and genotyping assays. An HIV-1-infected mother enrolled in Bangkok in a perinatal transmission study was identified independently as subtype B by V3 serotype by St. Mary's and HIV/AIDS Collaboration laboratories using different in-house assays. Her plasma was also screened for other HIV-1-specific immune responses, yielding a pattern of antibody reactivity similar to other subtype E sera. The genetic subtype of the isolate was identified by heteroduplex mobility assay (HMA) to further characterize it. Analysis results suggest that the woman was infected with HIV-1 subtype E. The env region encoding C2-V3 was subsequently sequenced to clarify the discordant results between the V3 serotype B and the genetic subtype E.^ieng

A comparison of full-length glycoprotein 120 from incident HIV type 1 subtype E and B infections in Bangkok injecting drug users with prototype E and B strains that are components of a candidate vaccine.

Complete gp120 sequence information was obtained from eight persons with incident HIV-1 infections (four subtype E and four subtype B) who were part of a prospective injecting drug user (IDU) cohort in Bangkok, Thailand, during 1996-1998. The incident subtype E strains were similar to the prototype subtype E strain CM244 isolated in 1992 in northern Thailand. The incident subtype B strains displayed divergence, in both overall genetic distance and other significant gp120 characteristics, from the prototype North American subtype B strain HIV-MN. Recombinant gp120s derived from CM244 and HIV-MN strains are components of a vaccine that is undergoing phase III efficacy testing, begun in March 1999, among Bangkok area IDUs. The information presented here will be important in the evaluation of any breakthrough HIV-1 infections occurring among vaccinees during the vaccine trial and in ongoing vaccine development efforts in Thailand.

Production of a novel viral suppressive activity associated with resistance to infection among female sex workers exposed to HIV type 1.

To investigate mechanisms of natural resistance to human immunodeficiency virus type 1 (HIV-1), we obtained blood samples from eight women who remained HIV-1 negative after > 3 years of high-risk sex work in Chiang Rai, Thailand. CD4+ T lymphocytes from these highly exposed, persistently seronegative (HEPS) women were readily infectable in vitro with HIV-1 subtypes B and E. Autologous CD8+ cell suppression of both HIV-1 subtypes was evident in HEPS infection cultures, but to an extent also observed in cultures from non-HIV-exposed individuals. Furthermore, production of beta-chemokines was not enhanced in HEPS cultures. However, HEPS cultures displayed significantly enhanced production of a soluble activity that suppressed postintegrated HIV-1 replication. This activity was the unique product of CD4+ T cell and monocyte cocultures. Therefore, although HEPS individuals are apparently susceptible to infection, the production of a postintegrated HIV-1 suppressive activity during monocyte-T cell interactions might protect against the establishment of infection by limiting viral dissemination.

Evaluation of a sensitive/less-sensitive testing algorithm using the 3A11-LS assay for detecting recent HIV seroconversion among individuals with HIV-1 subtype B or E infection in Thailand.

The development of a serologic algorithm to determine recent HIV seroconversion, using sensitive/less-sensitive testing strategies, has generated widespread interest in applying this approach to estimate HIV-1 incidence in various populations around the world. To evaluate this approach in non-B subtypes, longitudinal specimens (n = 522) collected from 90 incident infections among injecting drug users in Bangkok (subtype B infection, n = 18; subtype E infection, n = 72) were tested by the 3A11-LS assay. Standardized optical density (SOD) was calculated, using median values, and the window period between seroconversion as determined by sensitive and less sensitive tests was estimated by a maximum-likelihood model described previously. Our results show that the mean window period of the 3A11-LS assay was 155 days (95% CI, 128-189 days) for subtype B but was 270 days (95% CI, 187-349 days) for subtype E specimens from Thailand. About 4% of individuals with incident subtype E infections remained below the threshold (SOD of 0.75), even 2 years after seroconversion. Among the patients with clinical AIDS and declining antibodies, none of the 7 individuals with subtype B, but 10 (8.7%) of 115 with subtype E infections, were misclassified as recent infections. Lowering the cutoff to an SOD of 0.45 for subtype E specimens resulted in a mean window period of 185 days (95% CI, 154-211 days), with all individuals seroconverting, and reduced the number of subtype E-infected patients with AIDS who were misclassified as having recent infection to 2.6%. Our results demonstrate that the 3A11-LS assay has different performance characteristics in detecting recent infections among individuals infected with subtypes B or E. Determining appropriate cutoffs and mean window periods for other HIV-1 subtypes will be necessary before this approach can be reliably implemented in settings where non-B subtypes are common.