Intrapartum and neonatal zidovudine treatment in reduction of perinatal HIV-1 transmission in Bangkok.

OBJECTIVE: To evaluate the efficacy of zidovudine (ZDV) administered during labor and to the infants in the first 6 weeks of life in reduction of perinatal HIV-1 transmission. DESIGN: Open label clinical trial. SITE: King Chulalongkorn Memorial Hospital, Bangkok, Thailand. MATERIAL AND METHOD: One hundred asymptomatic, antiretroviral naive HIV-1 infected pregnant women who had either late or no prenatal care were recruited from the obstetric service of King Chulalongkorn Memorial Hospital, Bangkok, Thailand. They were given ZDV 300 mg orally every 3 hours during the intrapartum period until delivery. ZDV syrup 2 mg/kg orally every 6 hours were given to the infants immediately after birth for 6 weeks. Breast feeding was not allowed. Infant's blood for HIV-1 PCR test was obtained at age 1 day, and 1, 3 and 6 months. HIV-antibody test was determined at age 18 months. Infants with at least one positive HIV-1 PCR test performed at or after 1 month of age or positive HIV-antibody test at age 18 months were classified as HIV-1 infected infants. RESULTS: There were 100 healthy infants delivered without complication. Fourteen infants were excluded due to; 13 lost to follow-up and 1 drug intolerance. Of the remaining 86 infants who were followed-up, 27 infants (31.4%) did not receive intrapartum ZDV treatment and 9 infants were HIV-1 infected. The perinatal transmission rate was 10.5 per cent, (95% CI 3.9, 17.1). CONCLUSION: The result of this study suggests that intrapartum oral ZDV treatment in asymptomatic HIV-1 infected mothers together with ZDV treatment in the neonates for 6 weeks can reduce the rate of perinatal HIV-1 transmission. This regimen may be an alternative treatment for prevention of HIV-1 infection in infants born to HIV-1 seropositive mothers who have had either late or no prenatal care.

Update on HIV/AIDS in Thailand.

Thailand experienced its first case of AIDS in 1984. Approximately 800,000 Thais were infected with HIV in 1995 and 1 million Thais became infected by the year 2000. There have been 5 major epidemic waves: among male homosexuals (started 1984-5), intravenous drug users (started 1988), female commercial sex workers (started 1989), male clients (started 1990), and housewives and the newborn (started 1991). Approximately 96 per cent of HIV-1 infected Thais carried recombinant subtype A/E, the rest carried B'. In a male seroconvertors cohort of 235 cases, median time to show CD4 <200 cells/microL was 6.8 years. Five years survival was significantly lower than that of the other subtype B seroconvertors study, i.e., 82 per cent compared to 90 per cent. Interestingly, 13.5 per cent of seronegative Thais showed homozygous SDF1-3'A polymorphism, which suggests that approximately one-tenth of Thais may become long-term non-progressors after HIV-1 infection. Primary HIV infection syndrome is rare among Thai patients (1.1%). In contrast, it was 50-90 per cent in Western cohorts. In early symptomatic patients, one-third developed pruritic pappular eruptions (PPEs). In advanced stage, disseminated tuberculosis, Pneumocystis carinii pneumonia (PCP), cryptococcosis, and esophageal candidiasis are commonly found. In Northern Thailand, however, Penicillium marneffei infection or penicillosis is more common than cryptococcosis. The recent understanding of HIV pathogenesis suggests that HIV eradication is unlikely to be achievable with current strategies. Several National HIV treatment guidelines including the Thai guideline have been recommended treatment with triple antiretroviral regimen when patients become symptomatics or CD4+ <200. Current development of antiretroviral therapy which includes new agents, new formulas, and pharmacokinetic enhancements, is directed to better potency, higher genetic resistant barrier, less pill burden, and once a day dosing. These will ultimately improve the adherence and the long-term effectiveness of antiretroviral treatment. In reality, however, although the cost of triple regimen is dramatically declining, many patients still can not afford it. Primary prophylaxis and early diagnosis and treatment of opportunistic infection should be considered in patients with CD4+ <200 cells/microL. Modified short course ZDV studies and donation campaigns for preventing mother-to-child transmission, clinical trials to investigate the best use of expensive anti HIV medications in a poor resource setting have been or are being conducted. Nine phase I/II HIV-1 vaccine trial protocols have been or are being tested. A phase III trial of gp120 subtype B/E (AIDSVAX, VaxGen) was started in 1999, a total of 2,500 volunteers will be enrolled, and interim analysis is planned for August 2002. Thai investigators are also participating in pre-clinical development of recombinant BCG and DNA vaccines. Multidisciplinary and multi-level approaches, both by the government and private sectors, have had a positive impact on the HIV epidemic as shown by the declining seroprevalence of HIV infection in Thai male conscripts, and of major sexually transmitted diseases in men. Nevertheless, more effort at the grass roots level is needed to ensure further success and sustainability of the control of the HIV epidemic in Thailand.

Short course zidovudine maternal treatment in HIV-1 vertical transmission: randomized controlled multicenter trial.

A multicenter randomized, double blind, placebo-controlled clinical trial was conducted to evaluate the effectiveness of a short course of oral zidovudine (ZDV) treatment in HIV-1 infected pregnant women, starting at 38 weeks of gestation plus ZDV infusion during labor until delivery, to reduce HIV-1 vertical transmission in non-breast fed infants. One hundred and eighty two asymptomatic antiretroviral naïve HIV-1 infected pregnant women were enrolled. Each patient was randomly allocated into either the ZDV or placebo group. The ZDV group received 250 mg ZDV orally twice a day initiated at 38 weeks' gestation until the onset of labor. During the intrapartum period, ZDV infusion at the rate of 2 mg/kg was administered within the first hour and then continuously infused at the rate of 1 mg/kg/h until delivery. The placebo group received an identical capsule during pregnancy and normal saline infusion during labor until delivery. HIV-1 transmission was documented by nested polymerase chain reaction in infants at birth and at 1, 3 and, 6 months of age. The estimated HIV-1 vertical transmission rate was 14.9 per cent (95% CI = 11.1 to 18.7) and 16.3 per cent (95% CI = 12.3 to 20.9) in ZDV and placebo group, respectively (p > 0.05). The short course ZDV in antiretroviral naïve pregnant women initiated at 38 weeks' gestation plus intrapartum ZDV infusion without treatment in the infants was not effective to prevent HIV-1 vertical transmission.

Intrapartum zidovudine infusion alone failed to reduce both maternal HIV-1 viral load and HIV-1 infection in infant.

A pilot clinical trial to assess the efficacy of intrapartum zidovudine (ZDV) infusion alone in the reduction of maternal viral load and its potential role in preventing vertical transmission of HIV-1. Twenty six, asymptomatic antiretroviral naïve HIV-1 infected pregnant women who had no prior antenatal care and were in labor were enrolled. Each patient received ZDV infusion at the rate of 2 mg/kg within the first hour. ZDV was then continuously infused at 1 mg/kg/h until delivery. Maternal plasma HIV-1 RNA prior to the commencement of ZDV infusion and within an hour after delivery were measured. HIV-1 transmission was documented by nested polymerase chain reaction in infants at six months of age. Median maternal plasma HIV-1 RNA prior to the ZDV infusion and after delivery was 29,401 and 32,555 copies/ml respectively, (p>0.05). The estimated HIV-1 transmission rate was 19.2 per cent (95% CI = 4-34). This result suggested that in asymptomatic HIV-1 infected pregnant women who were antiretroviral naïve and had no prior antenatal care, intrapartum ZDV infusion alone failed to reduce maternal HIV-1 viremia and the transmission rate of HIV-1.

Interleukin-1beta level in gingival crevicular fluid of patients with active periodontitis.

Previous studies revealed that interleukin-1beta (IL-1beta) was detectable in gingival crevicular fluid (GCF) of patients with periodontitis, and the level was increased in level in gingival tissue extracts of active periodontal disease sites (defined as attachment loss > or = 2.5 mm over the preceding 2 months) compared to inactive sites or healthy sites. The present study evaluated the relationship of IL-1beta level in GCF and periodontal disease status. GCF was collected with Periopaper strips from 34 disease-active and 45 disease-inactive teeth in 11 untreated periodontitis patients and from 60 teeth in 15 healthy control subjects. Disease activity was defined as attachment loss of > or = 2.5 mm in at least one site of a tooth as determined by sequential probing. The absorbed GCF volume was determined using a Periotron 6000 and the crevicular IL-1beta level was determined using IL-1beta monoclonal antibody (Otsuka Pharmaceutical, Japan). IL-1beta was below the detection level of the assay (6 pg/ml) in the healthy control group but was detected in most teeth of the periodontitis group. However, disease-active teeth had higher IL-1beta level (Mann-Whitney U-test, p < 0.05) than disease-inactive teeth (mean total IL-1beta of 5.89 +/- 7.88 pg/tooth and 1.72 +/- 2.28 pg/tooth; mean concentration of 1.6 +/- 2.5 ng/ml and 0.6 +/- 0.83 ng/ml, respectively). The level of IL-1beta showed no correlation with probing depth, but had significant correlation (p < 0.05) with the extent of attachment loss. This study suggests that the level of IL-1beta in GCF may have a predictive value for determining active and inactive periodontal status.

Immune responses to measles immunization and the impacts on HIV-infected children.

This prospective cohort study was conducted to determine the seroconversion rate and the pattern of antibody response to measles vaccine administered at age 9 months in HIV infected and non-infected children born to HIV-1 seropositive mothers. Thirty children born to HIV-1 seropositive mothers and 3 born to HIV-1 seronegative mothers were recruited. One single dose of Schwarz strain of measles virus vaccine (Rouvax) was given to every child at 9 months of age. Clinical status and measles antibody levels were evaluated at the time just before vaccination, 2 and 12 weeks post-vaccination. Antibody was measured by an enzyme immunoassay commercial kit (Enzygnost, Dade Behring Manufacturer, Germany). Children were classified into 3 groups, groups 1 and 2 were children with and without HIV infection respectively. Group 3 children were those born to HIV-1 seronegative mothers. Of the 33 enrolled children, 16, 14 and 3 were classified as groups 1, 2 and 3 respectively. Four children, 2 of each, in groups 1 and 3 did not complete the study. Group 3 was excluded due to the small number of children recruited. There was no short term complication and no measles infection noted during the course of study. None of the children had pre-existing antibodies. The median (range) of CD4 count and CD4/CD8 ratio measured at the time of vaccination were statistically different between groups 1 and 2 children. Group 2 children had better antibody response than group 1 in terms of seroconversion rate and median of antibody levels at 12 weeks post-vaccination. Only 7 of 29 children (24.1%) had detectable measles antibodies at 2 weeks post-vaccination. A decrease in antibody was noted in 2 symptomatic HIV infected children as their disease had progressed. Various potential predictors of measles vaccine responses in HIV infected children including CD4 count and CD4/CD8 ratio were not statistically different between the responders and non-responders. All 4 asymptomatic HIV infected children were responders. This study demonstrated that all of the children had already lost their maternal acquired antibodies at age 9 months. HIV infected children had a poorerantibody response to measles vaccine than the non-infected children.

Safety and immunogenicity of Bacillus Calmette-Guerin vaccine in children born to HIV-1 infected women.

This prospective cohort study was conducted to determine the complication of Bacillus Calmette-Guerin (BCG) vaccination given to newborn infants born to HIV-1 seropositive mothers and to compare the tuberculin reaction 9 months after BCG vaccination between HIV-1 infected and non infected children. Two hundred and twenty-three infants with BCG immunization at birth were examined. No BCG complication was noted. Tuberculin skin tests were performed on 126 children (56.5%). Eleven of them were excluded because of failure to have skin tests read at 48 hours. Of the 115 infants enrolled to this study, 15 (13%) had no BCG scar and 50 (43.5%) had no tuberculin reaction. Twenty-six children were classified as group 1 or HIV-1 infected children and 89 children were group 2 or HIV-1 non infected. Group 1 children had a smaller tuberculin skin response (X+SD) than group 2 (1.15 +/- 2.82 vs 4.64 +/- 4.29 mm; p < 0.0001). Mean weight + SD of group 1 children was also significantly less than those in group 2 (8,013 +/- 741 vs 8,540 +/- 984 g; p < 0.05). The proportion of children with non reactivity to the tuberculin test, a negative tuberculin test and no BCG scar in group 1 was significantly higher than that in group 2 (76.9% vs 33.7%, 92.3% vs 52.8% and 36.4% vs 6.7% respectively; p < 0.0001 for all). But, the proportion of non reactivity to the tuberculin test in children with or without BCG scar of each group was not different (p > 0.05). Positive tuberculin tests were 7.7% and 47.2% in group 1 and 2 respectively. None of the children with positive tuberculin tests had clinical evidence of tuberculosis. The findings of this study indicate that BCG vaccine given to newborn infants of HIV-1 seropositive mothers is safe. Although tuberculin skin responses of HIV-1 infected children are less than those of HIV-1 non-infected children, it is possible that BCG vaccine might protect these children from developing severe tuberculosis.

The risk of occupational HIV exposure among Thai healthcare workers.

To analyze the incidence of occupational exposure to HIV in a large group of healthcare workers at the 2 Thai Red Cross hospitals, prospectively collected during a seven-year period in order to find out the causes and circumstances that prone to exposure, the interventions that may minimize the exposure and the consequences of the accidents. The first 200 incident reports from 198 hospital workers of the Thai Red Cross Society who had occupational exposure to HIV-infected blood and body fluids during 1991-1997 were analyzed. We analyzed the demographic data, the timing and place of exposure, the nature and cause of exposure, HIV status at baseline and at follow-up at 3, 6 and 12 months as well as the received antiretroviral prophylaxis. All of the 198 HCW had negative anti-HIV at baseline and remained negative throughout the one-year follow-up although only 55% submitted the results of their anti-HIV testing at 6 months. However, none claimed for work-related life insurance against HIV during those 7 years indicating that nosocomial rate of transmission is less than 1 in 200 or less than 0.5%. Analysis of the incidents indicated that the risk group was the 20-40 years old nursing personnel who worked in the medical wards during the regular working hours. The procedures that were responsible for most of the injuries were venepuncture, intravenous access, injection and waste collection. Most of the injuries could be prevented if the work place safety guidelines were strictly followed and if personnel were more careful at work. The results can be used to implement more effective preventive measures for hospitals in Thailand. Postexposure management at the Thai Red Cross hospitals conformed with the international guidelines. However, only 78% of those who should receive postexposure prophylaxis were recommended for treatment and only 69% of those recommended actually took the treatment. This emphasizes the need to educate clinicians involved in postexposure care as well as to ensure them and the injured subjects about the safety of the antiretroviral prophylaxis.

IL-1beta, IL-6 and TNF-alpha in synovial fluid of patients with non-gonococcal septic arthritis.

Interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are the main proinflammatory cytokines responsible for the inflammatory process and cartilage destruction of inflammatory arthropathies. The present study sequentially measured the concentrations of these cytokines and their proportions of detectable levels in the synovial fluid (SF) of 23 patients with non-gonococcal (GC) septic arthritis before and after treatment. Persistently high concentrations and proportions of IL-6 and TNF-alpha were found up to day 7 of treatment, while SF IL-1beta concentration declined significantly after day 7 (p = 0.036). SF IL-1beta and TNF-alpha correlated with each other significantly and with SF WBC counts (p < 0.01). Positive correlations between SF IL-1beta concentration and joint effusion (p < 0.01) and between SF TNF-alpha concentration and joint tenderness (p < 0.001) were observed. SF IL-1beta and TNF-alpha were significantly higher in patients with local complications of septic arthritis. In conclusion, high levels of IL-1beta, IL-6 and TNF-alpha were detected in SF of patients with non-GC septic arthritis. Only IL-1beta decreased significantly after day 7 of treatment, but IL-6 and TNF-alpha concentrations were persistently high. SF IL-1beta and TNF-alpha may be useful in predicting the outcome and complications of patients with this disease.