Dwip Kitayaporn

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.

Estimating the number of HIV-infected injection drug users in bangkok : a capture-recapture method

OBJECTIVES The purpose of the study was to estimate the number of injection drug users infected with the human immunodeficiency virus (HIV) in Bangkok to allow planning for health services for this population. METHODS A two-sample capture-recapture method was used. The first capture listed all persons on methadone treatment for opiate addiction from April 17 through May 17, 1991, at 18 facilities in Bangkok. The second capture involved urine testing of persons held at 72 Bangkok police stations from June 3 through September 30, 1991. Persons whose urine tests were positive for opiate metabolites or methadone were included on the second list. RESULTS The first capture comprised 4064 persons and the recapture 1540 persons. There were 171 persons included on both lists, yielding an estimate of 36,600 opiate users in Bangkok. Existing data indicate that 89% of opiate users in Bangkok inject drugs and that about one third are infected with HIV, yielding an estimate of approximately 12,000 HIV-infected injection drug users in Bangkok in 1991. CONCLUSIONS During the 1990s the number of cases of acquired immunodeficiency syndrome (AIDS) and other HIV-related diseases, including tuberculosis, in the population of HIV-infected injection drug users in Bangkok will increase dramatically, placing new demands on existing health care facilities. The capture-recapture method may be useful in estimating difficult-to-count populations, including injection drug users.

Incarceration and risk for HIV infection among Injection drug users in Bangkok

&NA; Objective: To assess potential multiple relationships between incarceration and HIV infection among injecting drug users (IDUs) in Bangkok. Previous cross‐sectional studies have shown strong relationships between incarceration and HIV infection but have not been able to assess potential causal pathways. Methods: Injection drug users seen at methadone treatment programs in Bangkok were screened during 1995 to 1996 for enrollment into the study. With informed consent, 1,209 seronegative IDUs were enrolled in a cohort study to determine HIV incidence and identify factors associated with incident infections. Follow‐up visits were conducted every 4 months, with HIV testing and assessment of risk behaviors. Results: Overall incidence rate was 5.8 per 100 person‐years (95% confidence interval [CI], 4.8‐6.8) of follow‐up. A four‐step “injection risk” scale was constructed that included less frequent than daily injection, daily injection, daily injection with reported sharing of injection equipment, and injection while incarcerated. This scale was strongly related to HIV incidence, with incidence approximately doubling for each step in the scale. Incidence rate for follow‐up periods that contained drug injection while incarcerated was 35/100 person‐years at risk. In multivariate analyses, incarceration was related to incident HIV infection in multiple ways: previous incarceration and recent incarceration without drug injection, and the injection risk scale were all independently predictors of incident HIV infection. Conclusions: Incarceration is related to incident HIV infection through multiple pathways. Previous incarcerations are likely to serve as markers for unmeasured highrisk behaviors, and it is also highly likely that HIV is transmitted during periods of incarceration. Programs to reduce HIV transmission in jails and prisons, including drug abuse treatment of inmates and programs to reduce the likelihood of incarceration of IDUs, are needed urgently. Given the current diffusion of injecting drug use, of HIV infection among drug injectors, and of the common policy of incarcerating drug users, it is very likely that the problem of HIV transmission in jails and prisons is increasing in many countries throughout the world.

HIV Type 1 Incidence Estimates by Detection of Recent Infection from a Cross-Sectional Sampling of Injection Drug Users in Bangkok: Use of the IgG Capture BED Enzyme Immunoassay

Development of serologic tests to detect recent HIV-1 infection has generated worldwide interest in applying this approach to estimate incidence. We previously devised an IgG-capture BED-EIA (or BED-CEIA) that detects increasing levels of anti-HIV IgG following seroconversion to identify recent infection and to estimate incidence among persons infected with diverse HIV-1 subtypes worldwide. Injection drug users (IDUs; n = 1969) were screened in 1996 for participation in a prospective cohort study. Serum specimens from 594 IDUs were HIV-1 seropositive (30.2%) and were tested with the BED-CEIA. The proportion of recent infections and estimated incidence by different epidemiological risk factors were compared with incidence data measured from the prospective cohort. Of 594 HIV-1-seropositive specimens, 113 (19%) were identified as recent infections. Overall, the estimated annual incidence among persons screened was 17.3%/year (95% CI, 12.8-24.2%/year) compared with 9.0%/year (95% CI, 6.7-11.9%/year) measured from the prospective cohort during the same time period. Estimated incidence was higher among younger aged and unemployed IDUs as well as among those who injected more frequently, confirming previously reported risk factors from this prospective cohort. As persons screened from a cross-sectional sampling probably have higher risk for HIV than selected uninfected individuals who choose to participate and receive risk reduction counseling in a longitudinal cohort study, use of this or other serologic testing strategies to identify populations with high incidence (such as for HIV vaccine trials) may overestimate incidence measured from prospective cohorts.

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.

Willingness of injection drug users to participate in an HIV vaccine efficacy trial in Bangkok, Thailand

We assessed willingness to participate in an HIV recombinant gp120 bivalent subtypes B/E candidate vaccine efficacy trial among 193 injection drug users (IDUs) attending drug treatment clinics in Bangkok, Thailand. IDUs previously enrolled in a prospective cohort study were invited to group sessions describing a potential trial, then completed questionnaires assessing comprehension and willingness to participate. A week later, they completed a follow-up questionnaire that again assessed comprehension and willingness to participate, as well as barriers to and positive motives for participation, with whom (if anyone) they talked about the information, and whether others thought participation was a good, bad, or neutral idea. At baseline, 51% were definitely willing to participate, and at follow-up 54%; only 3% were not willing to participate at either time. Comprehension was high at baseline and improved at follow-up. Participants who viewed altruism, regular HIV tests, and family support for participation as important were more willing to volunteer. Frequency of incarceration and concerns about the length of the trial, possible vaccine-induced accelerated disease progression, and lack of family support were negatively associated with willingness. Overall, IDUs comprehended the information needed to make a fully informed decision about participating in an rgp120 vaccine efficacy trial and expressed a high level of willingness to participate in such a trial.

Phase I/II study of a candidate vaccine designed against the B and E subtypes of HIV-1.

SummaryA phase I/II trial of a candidate vaccine to prevent HIV infection was carried out in Bangkok, Thailand, testing AIDSVAX B/E (VaxGen, Inc., Brisbane, CA), a bivalent subunit vaccine prepared by combining recombinant gp120 from a subtype B virus (HIV-1MN) with gp120 from a subtype E virus (HIV-1A244) in alum adjuvant. The studies provide human data on the immunogenicity of various dose combination of non–subtype B vaccine antigens. The results suggest that AIDSVAX B/E is safe and immunogenic in humans. The optimal dose for humans in developing countries was 300 μg of each antigen (B and E). Clade E responses were measurably increased by immunizing with gp120 B/E over B alone. Using the B/E combination did not interfere with the response to either clade. Antibodies to AIDSVAX B/E were able to bind to oligomeric gp120 on the surface of cells infected with primary isolates of HIV-1.

Clinical presentation of hospitalized adult patients with HIV infection and AIDS in Bangkok, Thailand

OBJECTIVE To characterize the clinical spectrum of disease and immune status of adult HIV-1-infected patients in Bangkok. DESIGN Cross-sectional survey of hospital admissions. METHODS From November 1993 through June 1996, demographic, clinical, and laboratory data were collected from HIV-infected inpatients (> or =14 years old) at an infectious diseases hospital. RESULTS Of 16,717 persons admitted, 3112 (18.6%) were HIV-seropositive, 2261 of whom were admitted for the first time. Of 2261, 1926 (85.2%) were male, 1942 (85.9%) had been infected heterosexually or by means not related to drug use, 319 (14.1%) were injection drug users (IDUs), and 1553 (68.7%) had AIDS. The most common AIDS-defining conditions were extrapulmonary cryptococcosis (EPC; 38.4%), tuberculosis (TB; 37.4%), and wasting syndrome (WS; 8.1%). IDUs were more likely (p < .05) to have TB or WS but less likely (p < .05) to have EPC or Pneumocystis carinii pneumonia than patients with no history of injection drug use. Lymphocyte counts were measured for 2047 (90.5%) patients; 81.8% had < or =1500 lymphocytes/microl. CONCLUSION These HIV-infected patients were admitted with severe immunosuppression. Cryptococcosis and TB are major problems and differ in prevalence among IDUs and persons infected sexually. Clinical and immunologic information is critical in improving the lives of HIV-infected persons in Asia through prevention, treatment, and prophylaxis.

Survival of Aids Patients in the Emerging Epidemic in Bangkok, Thailand

Survival from the time of AIDS diagnosis to death was determined retrospectively among Thai patients (> or = 13 years old) who attended a public tertiary care infectious disease hospital in a suburb of Bangkok, Thailand, from February 1987 through February 1993. An AIDS diagnosis was based on the 1987 Centers for Disease Control (CDC) definition, except Penicillium marneffei infection was included as an AIDS-defining condition. Of 329 AIDS patients, 152 (46.2%) had died. The median age at diagnosis was 31.5 years (range, 18-74) 306 patients (93.0%) were males. Reported risk categories were heterosexual contact (55.2%), injecting drug use (IDU, 22.6%), male homosexual or bisexual contact (9.5%), and unidentified risk or other (12.7%). Median survival time (Kaplan-Meier) for all patients was 7.0 months; 1-year survival probability was 39.2% (95% confidence interval [CI] = 31.5-46.9%). Coxs proportional hazards model showed three factors associated with survival: age, reported risk category, and presenting diagnosis. Patients aged 26 to 35 years survived longer (median survival time, 10.6 months; relative hazard [RH] = 0.61, 95% CI = 0.44-0.85, referent: others), as did patients in sexual risk categories (median survival time, 7.3 months; RH = 0.59, 95% CI = 0.40-0.78, referent: IDU and other categories). A single presenting diagnosis of extrapulmonary tuberculosis was also associated with longer survival (median survival time, 19.9 months, RH = 0.55, 95% CI = 0.35-0.86, referent: other diagnoses). AIDS patients in the early phase of the epidemic in Bangkok have much shorter survival times than patients in developed countries, in part perhaps because they are often diagnosed late in the course of HIV infection. Increased attention should be given to the early diagnosis and treatment of these patients.

Recruitment screening and characteristics of injection drug users participating in the AIDSVAX B/E HIV vaccine trial Bangkok Thailand.

Objectives: To describe recruitment, screening and baseline characteristics of injection drug users (IDU) participating in a phase III HIV vaccine (AIDSVAX®B/E; VaxGen, USA) trial and to compare enrollment characteristics between trial participants and 1209 IDU from a 1995–1998 vaccine trial preparatory cohort for changes that might impact trial design assumptions. Methods: Enrollment for both studies was conducted at Bangkok narcotic treatment clinics, where a standardized questionnaire was administered on demographics, risk behavior and incarceration history over the previous 6 months. Results: During 1999–2000, 4943 IDU were screened for enrollment; successful sources of recruitment included clinic attendees (43.4%), an IDU referral program (20.4%) and preparatory cohort participants (14.7%). Of those screened, 1689 (34%) were HIV seropositive (HIV subtype B 23.6%; subtype E 76.4%). Of the 2545 enrolled, 93.4% were male. Compared with cohort IDU, trial IDU were younger (mean age: 28.8 versus 31.3 years), better educated (secondary level or higher: 67.2% versus 58.7%), and less likely to inject drugs daily (39.4% versus 90.4%); they were more likely to have been incarcerated (78.4% versus 65.7%), have recently injected stimulants (14.8% versus 5.8%) and tranquilizers (11.5% versus 2.3%), and obtained needles/syringes from a source other than a pharmacist (7.2% versus 3.9%) (all P ⩽ 0.003). Conclusions: IDU at high risk for HIV have been successfully enrolled in the AIDSVAX®B/E efficacy trial. Only minor epidemiologic differences were found at enrollment between trial and preparatory cohort IDU. The latter has proven critical in guiding trial design; results are expected in late 2003.