Bruce G. Weniger

Independent introduction of two major HIV-1 genotypes into distinct high-risk populations in Thailand.

To investigate the genetic heterogeneity and epidemiological distribution of human immunodeficiency virus type 1 (HIV-1) in Thailand, we determined proviral sequences for 63 HIV-1-infected patients in various risk groups from all over the country between April and July, 1991. Two distinct genotypes of HIV-1, A and B, were found to segregate by mode of transmission. Of 29 sexually infected patients, 25 (86%) had HIV-1 of genotype A and 4 (14%) had genotype B. Among 29 injecting drug users, probably parenterally infected, only 7 (24%) had genotype A and 22 (76%) had genotype B. This segregation is unlikely to have arisen by chance (p < 0.001). No patient was found to have dual infection. Nucleotide divergence averaged 3.4% among genotype-A-infected patients and 3.5% among genotype-B-infected patients, but 22.0% between the genotypes. 37 of 40 isolates (both genotypes) had the GPGQ tetrapeptide at the tip of the V3 loop, which is common in African HIV-1 strains but rare in North American and European strains, where the GPGR motif predominates. These findings suggest that the waves of HIV-1 infection in injecting drug users and in sexually infected patients in Thailand may not be epidemiologically linked. The nucleotide divergence data point to the separate introductions of the two genotypes in Thailand. Further studies in Thailand and neighbouring countries will be useful in the design and selection of candidate HIV vaccines.

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.

Safety and immunogenicity of varying dosages of trivalent inactivated influenza vaccine administered by needle-free jet injectors

To evaluate the perceived pain, other adverse events, and immunogenicity of influenza virus vaccine administered by needle-free jet injector (JI) compared with that of vaccine administered by needle and syringe (N&S), we randomly assigned 304 healthy young adults to receive one of three dosages (0.5, 0.3, or 0.2 ml) of the 1998-1999 season vaccine administered by either of two JI devices or by N&S. In multivariate analysis, female gender and JI administration were associated with higher levels of pain reported at the time of vaccination as well as with the occurrence of local injection site reactions following vaccination. Immune response did not vary significantly by dosage but administration by one JI device was associated with higher post-vaccination H1N1 antibody titers.

Maternal Virus Load and Perinatal Human Immunodeficiency Virus Type 1 Subtype E Transmission, Thailand

To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P<.001). No transmission occurred at <2000 copies/mL. On multivariate analysis, prematurity (adjusted odds ratio [AOR], 4.5), vaginal delivery (AOR, 2.9), low NK cell percentage (AOR, 2.4), and maternal virus load were associated with transmission. As RNA quintiles increased, the AOR for transmission increased linearly from 4.5 to 24.8. Two-thirds of transmission was attributed to virus load>10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission.

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.

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 (x2 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.

Experience from HIV incidence cohorts in Thailand : implications for HIV vaccine efficacy trials

From early 1990 to early 1992 Nelson et al. found the prevalence of HIV infection among rural northern Thailand village men aged >or= 15 years doubled from 5.3 to 10.4% and among village women of the same age range quadrupled from 0.5 to 2.3%. The incidence rates for HIV in these age groups were 3.2 per 100 person-years (PY) for men and 0.9 for women triple the rate for rural African men recently reported from Uganda an epicenter of the HIV pandemic in Africa. Thailand is likely to be among the first countries to begin trials of candidate vaccines. The protocol for the first Phase 1/Phase II trial was approved in early 1994 by the responsible review committees; by mid 1994 a branched peptide HIV-1 vaccine produced by United Biomedical Inc. is expected to be administered to healthy HIV-negative Thai volunteers by the Thai Red Cross. Other Phase I/Il trials are planned soon by the Vaccine Trials Center of Mahidol University Bangkok using a gp120 vaccine produced by Genentech Inc. The documented circulation of 2 distinct subtypes of HIV-1 in Thailand would permit vaccine trials that could measure cross-protection against wild viruses genetically heterologous to vaccine antigen. However all but one of the cohort studies have been among individuals at heterosexual risk among whom nearly all infections are with HIV-1 env subtype E/Thai genotype A (EA). In contrast IDU in Bangkok have both Ea and subtype B/Thai genotype B (Bb) in a ratio of about 1 : 3. Thus given their high incidence of 11 per 100 PY IDU might make excellent candidates for vaccine efficacy trials designed to study cross protection.

Identification of mixed HIV-1 / HIV-2 infections in Brazil by polymerase chain reaction.

Analysis of sera from hospitalized Brazilian patients by whole-virus lysate-based enzyme immunoassay and Western blot indicated that 0.4% were reactive to HIV-2 alone while 4% were reactive to both HIV-1 and HIV-2. When these sera were tested for HIV antibody by type-specific peptide enzyme immunoassays, dual seropositivity was confirmed in only 0.4% of patients. To define genetically the HIV strains within the population, we analyzed peripheral blood mononuclear cells from selected seropositive patients for the presence of HIV-1 and HIV-2 proviral DNA using the polymerase chain reaction (PCR). Independent primers/probes sets were used for the amplification and detection of viral sequences from the long terminal repeat (LTR), gag, and protease (prt) gene regions. Our findings confirmed the serologic evidence of HIV-2 in Brazil and determined the extent of mixed HIV-1 and HIV-2 infections. Detailed evaluation of the amplified viral protease sequences by endonuclease restriction analysis and DNA sequencing independently confirmed mixed HIV-1 and HIV-2 infections in the two patients seropositive for HIV-1 and HIV-2. The data further indicated that these isolates are distinct from the HIV laboratory standards. We interpret the combination of culture and PCR findings to demonstrate the presence of both HIV-1 and HIV-2 in Brazil.

Frequency and causes of vaccine wastage

UNLABELLED Assessing the frequency of vaccine wastage and the relative magnitude of its various causes may help to target efforts to reduce these losses and to husband funds for increasingly expensive vaccines. METHODS As a preliminary overview of wastage in the United States, 64 public-sector state and local health department immunization programs were polled in 1998 and 1999 for wastage recording practices. Actual wastage data were collected from a non-random subset of five states. Data on returns of wasted vaccine to manufacturers were analyzed from routine national biologics surveillance and from an ad-hoc survey. Excise tax credit requests for such returns between 1994 and 1999 were reviewed. RESULTS Rates of wastage among the five states ranged from about 1 to 5% in 1998, with an overall rate of 2.6% among 57 immunization programs in 1999. Categories of wastage used by the health departments varied widely, with overlapping classifications. The major causes appeared to be refrigeration (cold chain) lapses, followed by expiration. Overall rates of vaccine returns varied up to 8% by manufacturer, and from 1 to 50% by vaccine type, with higher return rates generally found for lesser-used vaccines. CONCLUSIONS If these wastage estimates of 1-5% applied nationally, in 1998 there would have been approximately US dollars 6-31 million worth of unused vaccine in the public sector alone. The two most common forms of wastage reveal the potential value of developing vaccines with improved heat stability and longer shelf lives. We propose six main classifications of vaccine wastage for use in routine monitoring and reporting.

The hidden costs of infant vaccination

Combination vaccines to minimize injections required for infant vaccination, and new vaccines with improved safety profiles, will pose increasingly complex choices for vaccine purchasers in the future. How much of a premium to pay for such vaccines might be determined by taking into account (1) the psychological burden of multiple injections during a single clinic visit, and the costs of any additional visits to minimize these, and (2) the medical, work-loss, and incidental costs of common vaccine-associated symptoms. This cross-sectional survey included randomly-selected parents of 1-8-month-old infants who received vaccines in a Northern California health maintenance organization (HMO) in 1997. Interviewers called parents 14 days after the infants vaccination to administer a 10-minute closed-ended interview in English or Spanish. Parents were asked about infant symptoms after vaccination, their preferences regarding multiple injections and their (theoretical) willingness to pay to reduce the number of injections their infant would receive, or to avoid the adverse symptoms experienced. Among 1769 eligible infants, interviews were completed with parents of 1657 (93%). The psychological cost of multiple injections was estimated by the willingness of parents to pay a median of