Frequency of HIV-1 dual subtype infections, including intersubtype superinfections, among injection drug users in Bangkok, Thailand

OBJECTIVES: To estimate the frequency and incidence of dual HIV-1 subtype infections, including superinfections, among recent seroconvertors from a cohort of injection drug users (IDUs). METHODS: A total of 1209 HIV-negative IDUs were followed in a prospective cohort study at 15 methadone clinics in Bangkok, Thailand. After 2308 person-years (PY) of follow-up, 133 seroconverted to HIV-1, of which approximately 20% were subtype B and 80% were CRF01_AE (formerly called subtype E). Specimens from 126 individuals were available at time of first seropositive test and specimens from 80 of these 126 individuals were also available more than 12 months later. For each infected participant, we calculated the amount of time to superinfection, loss to follow-up, or to the closest visit more than 12 months after the time of initial seropositivity. RESULTS: Of all 126 seroconverters seen at the time of the first seropositive test result, there was no apparent case of concurrent dual subtype infection detected despite 2301 PY of observation. Overall, the incidence of superinfection was 2.2 per 100 PY [95% confidence interval (CI), 0.3-7.8]. The 1-year incidence of CRF01_AE superinfection following subtype B primary infection was 3.9 per 100 PY (95% CI, 0.1-21.9) and the incidence of subtype B superinfection following CRF01_AE primary infection was 1.5 per 100 PY (95% CI, 0.04-8.3). CONCLUSIONS: Determination of the frequency and incidence of dual HIV-1 subtype infection demonstrates that HIV-1 superinfection is not uncommon in a population with high HIV-1 incidence with more than one circulating strain.     

CDC international HIV prevention research activities among injection drug users in Thailand and Russia

The Centers for Disease Control and Prevention (CDC) has participated in collaborative HIV prevention research activities in injection drug users (IDUs) with the Bangkok Metropolitan Administration (BMA) in Bangkok, Thailand, from 1995 to the present and with the Orel AIDS Center in Orel Oblast, Russia, from 2001 to 2003. Studies in Bangkok have included an HIV prevention trial preparatory cohort from 1995 to 1998, a seroconverter cohort from 1998 to the present, a phase III trial of the AIDSVAX B/E gp 120 HIV vaccine from 1999 to 2003, and a phase II/III HIV prophylaxis trial with tenofovir scheduled to begin in 2005. Activities in Orel included a review of HIV surveillance data in 2001, focus group discussions and a case-control study with HIV-infected and-uninfected IDUs in 2001, a cross-sectional study with the female sex partners of male IDUs in 2002, and a community outreach intervention in 2002–2003. In Bangkok, 1,209 IDUs were enrolled in the preparatory cohort which revealed an HIV incidence of 5.8% per 100 person-years; 133 HIV-infected IDUs have been followed in the seroconverter cohort with >85% follow-up and HIV and tuberculosis care provided; 2,546 IDUs were enrolled in the HIV vaccine efficacy trial which was successfully completed with a followup rate of >95%, although the vaccine was not shown to be effective at reducing HIV incidence; and 1,600 IDUs will be enrolled in the daily tenofovir HIV prophylaxis trial in 2005. In Orel, initial focus group discussions and epidemiologic studies revealed low HIV knowledge and high rates of unsafe injecting and sexual practices among IDUs and their female sex partners; and educational campaigns and the community outreach intervention were developed and implemented. A steady decline in new HIV infections in IDUs was then observed in Orel in 2002–2003. CDC has participated in the conduct of successful collaborative HIV prevention research activities in Thailand and Russia over the past decade. The establishment of long-term relationships with in-country public health and community partners has been instrumental in the success of these efforts.     

Incarceration and risk for HIV infection among injection drug users in Bangkok.

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 high-risk 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.     

Subtype-specific transmission probabilities for human immunodeficiency virus type 1 among injecting drug users in Bangkok, Thailand.

The Bangkok (Thailand) Metropolitan Administration cohort of injecting drug users (IDUs) consisted of 1,209 IDUs initially seronegative for human immunodeficiency virus (HIV) who were followed from 1995 to 1998 at 15 Administration drug treatment clinics. At enrollment and approximately every 4 months thereafter, participants were assessed for HIV seropositivity. As of December 1998, there were 133 HIV type 1 seroconversions and approximately 2,300 person-years of follow-up. Of the 133 observed seroconversions, specimens from 126 persons were available for subtyping (27 subtype B, 99 subtype E). In this analysis, the authors assessed differences in subtype-specific transmission while controlling for important risk factors. The methodology used accounts for left truncation, interval censoring, and competing risks as well as for time-varying covariates such as each IDU's history of reported frequency of injection and of incarceration. Using plausible epidemiologic assumptions and controlling for behavioral risks, the authors found that a significantly higher transmission probability was associated with subtype E compared with subtype B in this population. Since many epidemiologic, virologic, and host factors can influence HIV transmission, it was difficult to conclude whether these differences in transmission probabilities were due to biologic properties associated with subtype.     

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.     

New HIV type 1 CRF01_AE/B recombinants displaying unique distribution of breakpoints from incident infections among injecting drug users in Thailand

The goals of this study were to identify and characterize recombinant human immunodeficiency virus type 1 (HIV-1) genomes among incident infections in a prospective cohort study of injecting drug users (IDUs) in Bangkok, Thailand. Through cross-sectional, comparative phylogenetic analysis of the protease and env (C2-V4) gene regions, subtype discordance was observed in HIV-1 sequences from 4 of 111 IDUs (3.5%). Near-full-length HIV-1 genome sequences of the four strains revealed that in all four, the gp120 sequences clustered with a CRF01_AE prototype, while the remainder of the genomes displayed distinct mosaic patterns, with multiple breakpoints between HIV-1 CRF01_AE and subtype B-like regions. Two of the four HIV-1 recombinant strains displayed a nearly identical mosaic structure, suggesting the possible emergence and spread of a potentially new circulating recombinant form of HIV-1. Further characterization of these and other recombinant genomes through long-term follow-up will be important in understanding the generation of viral diversity and escape from the hosts immune responses. This information will be especially important for vaccine development.     

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 < or = 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.     

Lack of increased HIV risk behavior among injection drug users participating in the AIDSVAX B/E HIV vaccine trial in Bangkok, Thailand

OBJECTIVE: To determine whether HIV vaccine trial participation leads to increased risk behavior through beliefs about vaccine protection against infection. METHODS: Changes in risk behavior were evaluated among 2545 injection drug users participating in the AIDSVAX B/E vaccine trial in Bangkok, enrolled from March 1999 to August 2000. Demographic characteristics, beliefs and risk behavior were assessed at baseline and every 6 months thereafter. Risk-reduction counseling was provided at every study visit. Generalized estimation-equation logistic regression analysis was used to study trends in risk behavior and associated factors. RESULTS: Participants were 93.4% male, their median age was 26 years, and 67.2% had at least secondary education. At baseline, 61.3% were receiving methadone detoxification and 20.9% were receiving methadone maintenance. From baseline to the 12-month follow-up visit, injection drug use decreased from 93.8% to 66.5% (P < 0.001) and needle sharing from 33.0% to 17.5% (P < 0.001). Multivariate analyses showed earlier follow-up time (at baseline and 6 months) and believing the vaccine to be efficacious associated with more-frequent injecting; younger age and lower education associated with less-frequent injecting. Earlier follow-up time (at baseline), younger age, and injection of methamphetamine and midazolam were associated with more-frequent needle sharing; methadone treatment and injecting less than weekly were associated with less-frequent needle sharing. CONCLUSIONS: Injection drug use and needle sharing decreased during the first 12 months of the trial. No increases in risk behavior in relation to beliefs about vaccine protection against HIV infection could be identified.     

Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand

BACKGROUND: In Thailand, phase 1/2 trials of monovalent subtype B and bivalent subtype B/E (CRF01_AE) recombinant glycoprotein 120 human immunodeficiency virus type 1 (HIV-1) vaccines were successfully conducted from 1995 to 1998, prompting the first HIV-1 vaccine efficacy trial in Asia. METHODS: This randomized, double-blind, placebo-controlled efficacy trial of AIDSVAX B/E (VaxGen), which included 36-months of follow-up, was conducted among injection drug users (IDUs) in Bangkok, Thailand. The primary end point was HIV-1 infection; secondary end points included plasma HIV-1 load, CD4 cell count, onset of acquired immunodeficiency syndrome-defining conditions, and initiation of antiretroviral therapy. RESULTS: A total of 2546 IDUs were enrolled between March 1999 and August 2000; the median age was 26 years, and 93.4% were men. The overall HIV-1 incidence was 3.4 infections/100 person-years (95% confidence interval [CI], 3.0-3.9 infections/100 person-years), and the cumulative incidence was 8.4%. There were no differences between the vaccine and placebo arms. HIV-1 subtype E (83 vaccine and 81 placebo recipients) accounted for 77% of infections. Vaccine efficacy was estimated at 0.1% (95% CI, -30.8% to 23.8%; P=.99, log-rank test). No statistically significant effects of the vaccine on secondary end points were observed. CONCLUSION: Despite the successful completion of this efficacy trial, the vaccine did not prevent HIV-1 infection or delay HIV-1 disease progression.