Suwanee Raktham

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.

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.

HIV/AIDS-related behavior change among injecting drug users in different national settings

ObjectivesTo identify factors associated with effective AIDS behavior change among injecting drug users (IDU) in different national settings. DesignCross-sectional surveys of IDU, with determination of HIV status. Trends in city HIV seroprevalence among IDU also used to validate effectiveness of behavior change. Setting and participantsSubjects recruited from drug-use treatment programs and outreach efforts in Bangkok, Thailand (n = 601), Glasgow, Scotland (n = 919), New York City, USA (n = 2539), and Rio de Janeiro, Brazil (n = 466). ResultsEvidence for the effectiveness of self-reported risk reduction was available for all cities. Univariate followed by multiple logistic regression analyses were used to identify factors associated with self-reported AIDS behavior change. Separate analyses were conducted for each city. Talking about AIDS with drug-using friends was significantly associated with behavior change in all four cities. Talking with sex partners about AIDS, educational level, knowing that someone can be HIV-infected and still look healthy, and having been tested previously for HIV were each significantly associated with behavior change in three of the four cities. ConclusionsDespite the substantial differences in these national settings, there were common factors associated with effective risk reduction. In particular, risk reduction appears to occur through social processes rather than through individual attitude change. HIV prevention programs need to explicitly incorporate social processes into their work.

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.

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.

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.

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.

High HIV Seroprevalence Epidemics among Injecting Drug Users; New York City and Bangkok

New York City, U.S.A., and Bangkok, Thailand, experienced two of the most important HIV epidemics among injecting drug users (IDUs) in the world. The epidemic in New York was the first, and by far the largest, HIV epidemic among IDUs. The Bangkok epidemic was notable both for the rapidity of HIV transmission among IDUs and for demonstrating that HIV transmission could occur among IDUs in developing countries. Rapid HIV transmission among IDUs in both cities was followed by large-scale behavior change and stabilization of HIV seroprevalence at high levels. The stabilization of seroprevalence includes unacceptably high rates of continued HIV seroconversions—estimated to be 4 per 100 person-years at risk or greater in both cities. Recent additional HIV prevention efforts in both cities—long-term methadone maintenance treatment in Bangkok and legal access to sterile injection equipment in New York—indicate possibilities for father reducing HIV transmission among IDUs in the two cities.