Philip A. Mock

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.

Maternal viral load and timing of mother-to-child HIV transmission Bangkok Thailand.

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.

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.

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.

Sexual initiation, substance use, and sexual behavior and knowledge among vocational students in northern Thailand.

CONTEXT Thailand has undergone dramatic social changes in the last two decades, yet little is known about factors related to sexual initiation among adolescents. METHODS A survey using the audio computer-assisted self-interviewing method was conducted to assess social and demographic characteristics, substance use, sexual behavior, and knowledge of HIV and STIs among 1,725 vocational school students aged 15-21 living in northern Thailand. Gender differences for these factors were evaluated using chi-square and Mann-Whitney U tests. Multivariate survival analysis using Cox proportional hazards models assessed associations between these variables and sexual initiation for each gender. RESULTS Males initiated sexual intercourse at an earlier age than females (median ages of 17 and 18, respectively). At any given age, sexual initiation was associated with having a nonagricultural background and using alcohol or methamphetamine (adjusted rate ratios, 1.3-2.9). For males, initiation was also associated with having parents who did not live together, having a friend as a confidant, tobacco use, high perceived risk for HIV and high STI knowledge (1.3-1.7). For females, other factors associated with earlier initiation were younger age at interview, living away from family, lacking a family member as a confidant, high perceived risk for STIs and ever having smoked marijuana (1.3-2.4). CONCLUSIONS Interventions to ameliorate the adverse consequences of early sexual initiation need to address social influences such as parents and peer groups. Programs should identify and target high-risk subgroups, such as those who are sexually experienced at an early age and those engaged in patterns of generalized risk-taking.

Determinants of depression and HIV-related worry among HIV-positive women who have recently given birth, Bangkok, Thailand

HIV-infected pregnant women have been the focus of considerable research related to biomedical issues of mother-to-child transmission worldwide. However, there have been few reports on the psychological well-being of new mothers with HIV, either in developed or developing countries. As part of a perinatal HIV transmission and family impact study in Bangkok, predictors of psychological scales were evaluated from interview data (N = 129) collected 18-24 months postpartum. Standardised questionnaires were used to assess depressive symptoms and HIV-related worry. Depressive symptomatology and HIV-related worry were common amongst these women. Multivariate logistic regression analysis identified several factors that predicted these psychological outcomes. High depression scores were associated with women who were no longer in a relationship with their partner (odds ratio (OR) 5.72, confidence interval (CI) 2.18-14.97) and who used venting coping strategies (OR 2.15, CI 1.44-3.21). Higher levels of HIV-related worry were associated with women whose babies were HIV-infected (OR 3.51, CI 1.28-10.69), who had not disclosed their HIV status to others (OR 3.05, CI 1.29-7.24) and who reported that their HIV-infection was something about which their family would be ashamed (OR 3.44, CI 1.34-9.77). Based on the current findings, intervention strategies we propose are psychological interventions which address disclosure issues, feelings of shame and coping strategies as well as financial assistance for single mothers. Interventions that require few resources such as group counselling or support merit special consideration.

Safety and acceptability of the candidate microbicide Carraguard in Thai Women: findings from a Phase II Clinical Trial

Objective:To determine the safety and acceptability of vaginal application of Carraguard, a carrageenan-derived candidate microbicide gel. Design:A randomized, placebo-controlled, triple-blinded clinical trial was conducted in Chiang Rai, northern Thailand. Methods:Women were asked to insert one applicator of study gel vaginally at least three times per week (with or without sex) and to use gel with condoms every time they had sex. Safety was assessed by visual inspection of the vagina and cervix, changes in vaginal flora and self-reported symptoms at day 14, month 1 and then monthly for up to 1 year. Acceptability was assessed through reported use of the gel, return of used and unused applicators, and quarterly interviews. Results:One hundred sixty-five women were randomized: 83 to Carraguard and 82 to the placebo (methylcellulose gel) group. Study gel use was similarly high in both groups throughout the trial with an average of four applicators per week. Carraguard use was not associated with abnormal genital clinical findings, abnormal vaginal flora, Pap smear abnormalities or other abnormal clinical signs or symptoms. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups. Participants in both groups reported high acceptability. Conclusions:Carraguard can safely be used an average of four times per week with or without sex and is acceptable to Thai women. A Phase III efficacy trial of Carraguard is warranted and is currently ongoing in South Africa.

Early diagnosis of HIV-1-infected infants in Thailand using RNA and DNA PCR assays sensitive to non-B subtypes.

Objectives: To evaluate the sensitivity and specificity of RNA and DNA polymerase chain reaction (PCR) for early diagnosis of perinatal HIV‐1 infection and to investigate early viral dynamics in infected infants. Design: A cohort study of 395 non‐breastfed infants born to HIV‐infected mothers in a randomized clinical trial of short‐course antenatal zidovudine. Methods: Infant venous blood specimens collected at birth, 2 months, and 6 months of age were tested by qualitative DNA and quantitative RNA PCR (Roche Amplicor). To determine sensitivity and specificity of DNA and RNA PCR, results were compared with later DNA PCR results and to antibody results at 18 months. The HIV‐1 subtype of the mothers infection was determined by peptide serotyping. Results: In the study, 92% of mothers were infected with subtype E. DNA PCR sensitivity was 38% (20 of 53) at birth, and 100% at 2 months (53 of 53) and 6 months (47 of 47). RNA PCR sensitivity was 47% (25 of 53) at birth and 100% (53 of 53) at 2 months. All samples that tested DNA‐positive tested RNA‐positive. Specificity was 100% for both DNA and RNA testing at all timepoints. For infected infants, the median viral load of RNA‐positive specimens was 407,000 copies/ml (5.6 log10) at birth, 3,700,000 copies/ml (6.6 log10) at 2 months, and 1,700,000 copies/ml (6.2 log10) at 6 months. Infant RNA levels at 2 and 6 months did not differ by maternal zidovudine exposure, or RNA level at birth. Conclusion: This RNA PCR assay performed well for diagnosing perinatal HIV subtype E infection, detecting nearly half of infected infants at birth, and 100% at 2 and 6 months, with 100% specificity. Infected infant viral RNA levels were very high at 2 and 6 months, and were unaffected by maternal zidovudine treatment.

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.

A Randomized, Placebo-controlled Trial to Assess the Safety and Acceptability of Use of Carraguard Vaginal Gel by Heterosexual Couples in Thailand

Objectives: To determine the safety and acceptability of use of Carraguard, a carrageenan-derived candidate microbicide gel, during sexual intercourse in women and men. Study Design: We conducted a 6-month randomized, placebo-controlled trial among sexually active, couples at relatively lower risk for HIV infection in northern Thailand. Methods: Women inserted 1 applicator of study gel vaginally every time the couple had sex. Safety was assessed by symptom report and genital examination of both partners and by changes in vaginal flora. Acceptability was assessed by participant interview. Results: Overall, 55 couples were randomized, 28 to Carraguard use and 27 to the methyl-cellulose placebo gel group. Retention and study gel use were similarly high in both study groups; use of gel without condoms was reported in more than 95% of vaginal sex acts. The 2 study groups were similar in the proportions of women and men with symptoms or with genital findings without epithelial disruption, of men with findings with epithelial disruption, and of women with abnormal genital flora, whereas more women in the placebo group had findings with epithelial disruption. Women and men in both groups reported that the gel and applicator were acceptable. Conclusions: Carraguard can safely be used an average of 2 to 3 times per week during sex and is acceptable to Thai women and men.