Monocyte-to-lymphocyte ratio as a predictor of TB among people living with HIV.

BACKGROUND: Diagnostic tools to identify incipient or subclinical TB stages will be helpful for preventive intervention. A simple biomarker to predict TB may be the monocytes to lymphocytes ratio (ML ratio) in peripheral blood.METHODS: We assessed the relationship between multiple time-updated ML ratio measurements and incidence of TB in people living with HIV (PLWH) after antiretroviral therapy (ART) was initiated. The ML ratio was updated at least every 6 months. TB incidence with corresponding 95% confidence intervals stratified according to time-updated ML ratio was calculated using ML ratio in quartiles.RESULTS: A total of 1305 PLWH were included in the analyses: 46 had incident TB and 1259 remained TB-free. The TB incidence rate was 10.3 (95% CI 7.1-14.9) cases/1000 patient-years (PYR) among participants with ML ratio ≥0.25 compared with 1.1/1000 PYR (95% CI 0.4-2.9) among those with ML ratio <0.15. At cut-point 0.23, the ML ratio provided a diagnostic area under the receiver operating characteristics curve (AROC) of 0.849 (95% CI 0.784-0.914) and a sensitivity of 85% and specificity of 71%.CONCLUSION: Increased ML ratio was predictive of incident TB among PLWH on or after ART. The ML ratio can be a simple tool to stratify the risk of TB in PLWH.

Correlation of selenium and zinc levels to antiretroviral treatment outcomes in Thai HIV-infected children without severe HIV symptoms.

BACKGROUND/OBJECTIVES: Deficiencies in antioxidants contribute to immune dysregulation and viral replication. To evaluate the correlation of selenium (Se) and zinc (Zn) levels on the treatment outcomes in HIV-infected children. SUBJECTS/METHODS: HIV-infected Thai children 1-12 years old, CD4 15-24%, without severe HIV symptoms were included. Se and Zn levels were measured by graphite furnace atomic absorption spectrometry at baseline and 48 weeks. Deficiency cutoffs were Se <0.1 µmol/l and Zn <9.9 µmol/l. Serum ferritin and C-reactive protein (CRP) were measured every 24 weeks. No micronutrient supplement was prescribed. RESULTS: In all, 141 children (38.3% male) with a median (interquartile range (IQR)) age of 7.3 (4.2-9.0) years were enrolled. Median baseline CD4% was 20%, HIV-RNA was 4.6 log(10)copies/ml. At baseline, median (IQR) Se and Zn levels were 0.9 (0.7-1.0) µmol/l and 5.9 (4.8-6.9) µmol/l, respectively. None had Se deficiency while all had Zn deficiency. Over 48 weeks, 97 initiated antiretroviral therapy (ART) and 81% achieved HIV-RNA <50 copies/ml with 11% median CD4 gain. The mean change of Se was 0.06 µmol/l (P=0.003) and Zn was 0.42 µmol/l (P=0.003), respectively. By multivariate analysis in children who received ART, predictors for greater increase of CD4% from baseline were lower baseline CD4% (P<0.01) and higher baseline Zn level (P=0.02). The predictors for greater decrease of HIV-RNA from baseline were higher baseline HIV-RNA and higher ferritin (both P<0.01). No association of CRP with the changes from baseline of CD4% or HIV-RNA was found. CONCLUSION: In HIV-infected Thai children without severe immune deficiency who commenced ART, no correlation between Se and ART treatment outcomes was found. Higher pre-ART Zn levels were associated with significant increases in CD4% at 48 weeks.

Assessing adherence in Thai patients taking combination antiretroviral therapy.

In settings where medications and viral load (VL) monitoring are limited by cost, clinicians need reliable ways to assess patient adherence to therapy. We assessed sensitivity and specificity of two self-reported adherence tools (a visual analogue scale [VAS] and the CASE [Center for Adherence Support Evaluation] adherence index), against a standard of detectable VL, with 288 patients from three sites in Thailand. We also assessed predictors of non-adherence. The sensitivity and specificity of the VAS <95% and CASE adherence index ≤11 against a VL >50 copies/mL were 26% and 90%, 19% and 95%, respectively. Against a VL ≥1000 copies/mL sensitivities increased to 55% and 36%, respectively, and specificities were unchanged. Attending a clinic not staffed by HIV specialists (odds ratio [OR] 3.14; 95% confidence interval [CI] 1.19-8.34) and being educated to primary school level or less (OR 2.24; 95% CI 1.01-4.94) were associated with self-reported adherence <95% on the VAS in multivariate analysis. Adherence assessed by the VAS was a more accurate predictor of detectable VL. Policy-makers in resource-limited settings should ensure that treatment centres are staffed with well-trained personnel aware of the importance of good patient adherence.

Genital shedding of HIV after scheduled treatment interruption.

This study assessed genital shedding of HIV in patients on intermittent combination antiretroviral therapy (cART) and assessed predictors of having detectable genital HIV RNA in 156 Thai patients with CD4 > 350 cells/µL and HIV RNA ≤50 copies/mL who were randomized to continuous therapy (CT, n = 65) or CD4-guided cART (n = 91). There were 383 matched genital and plasma HIV RNA samples (CT: 158, CD4 guided: 225). In 14 samples collected within eight weeks of treatment interruption, detectable HIV RNA was present in 29% of genital samples and 71% of plasma samples. In 55 samples collected after eight weeks of treatment interruption, detectable HIV RNA was present in 60% of genital samples and 98% of plasma samples. In 110 samples collected up to 96 weeks after treatment re-initiation, detectable genital HIV RNA was found in 8% of samples and all of these were within the first 17 weeks. Independent predictors of detectable genital HIV RNA were increasing age and increasing concentrations of HIV RNA in plasma. These findings support the role of cART in maintaining undetectable HIV RNA in genital secretions.

Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial.

BACKGROUND: Scheduled treatment interruptions are being evaluated in an effort to decrease costs and side effects of highly active antiretroviral therapy (HAART). A schedule of 1 week on and 1 week off therapy offers the promise of 50% less drug exposure with continuously undetectable HIV RNA concentration. METHODS: In the Staccato study 600 patients on successful HAART were to be randomized to either continued therapy, CD4-guided therapy, or one week on, one week off therapy. A scheduled preliminary analysis evaluated effectiveness in the 1-week-on-1-week-off arm. RESULTS: Of 36 evaluable patients, 19 (53%) had two successive HIV RNA concentrations > 500 copies/ml at the end of the week off therapy, and were classified as virological failure. Most of those who failed took didanosine, stavudine, saquinavir, and ritonavir (11 patients). In these patients, there was no evidence of mutations suggestive of drug resistance, and plasma saquinavir levels were within the expected range. Two of three patients failing on triple nucleotides had drug resistance mutations, but nonetheless responded to reintroduction of triple nucleotide therapy. One of two patients taking nevirapine, and one of eight taking efavirenz, also failed. Both had resistance mutations at the time of failure, but not at baseline. CONCLUSIONS: The 1-week-on-1-week-off schedule, as tested in the Staccato study, showed an unacceptably high failure rate and was therefore terminated.

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.

A randomized, open-label, comparative trial of zidovudine plus lamivudine versus zidovudine plus lamivudine plus didanosine in antiretroviral-naive HIV-1-infected Thai patients.

OBJECTIVE: To assess the efficacy and tolerability of a triple nucleoside reverse transcriptase inhibitor combination of zidovudine, lamivudine, and didanosine therapy. DESIGN: A randomized open-label trial. PATIENTS: Antiretroviral-naive HIV-infected patients with CD4+ cell counts of 100 to 500 cells/microl. METHODS: A total of 106 patients were randomly assigned to 300 mg of zidovudine (200 mg for body weight <60 kg) twice daily plus 150 mg of lamivudine twice daily plus 200 mg of didanosine (125 mg for body weight <60 kg) twice daily (n = 53) or to zidovudine plus lamivudine (n = 53) for 48 weeks. MAIN OUTCOME MEASURES: Degree and duration of reduction of HIV-1 RNA load and increase in CD4+ cell counts from baseline and development of drug-related toxicities. RESULTS: At 48 weeks, triple drug therapy showed greater declines in plasma HIV-RNA levels from the beginning of treatment than double drug therapy (1.86 vs. 1.15 log10 copies/ml, respectively; p <.001). The proportions of patients with HIV-RNA <50 copies/ml in an intention-to-treat analysis were 54.7% (29 of 53 patients) and 11.3% (6 of 53 patients) in the triple and double drug therapy, respectively (p =.001). There was no significant difference in increase of CD4 count. CONCLUSION: Triple drug therapy with zidovudine, lamivudine, and didanosine was significantly more effective in inducing sustained immunologic and virologic responses than the double combination of zidovudine and lamivudine.

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.

A randomized, double-blind trial of half versus standard dose of zidovudine plus zalcitabine in Thai HIV-1-infected patients (study HIV-NAT 001). HIV Netherlands Australia Thailand Research Collaboration.

BACKGROUND: Triple combination antiretroviral therapy, recommended as standard of care, is unaffordable for much of the developing world. OBJECTIVES: To establish whether half doses of zidovudine (AZT) and zalcitabine (ddC) are as effective as standard doses in a Thai population with lower body weight than Western populations and predominantly infected with HIV-1 subtype E. METHODS: A group of 116 antiretroviral naive patients, with CD4 cell counts 100-500 x 10(6) cells/l, were randomized to: AZT 200 mg three times daily plus ddC 0.75 mg three times daily versus AZT 100 mg three times daily plus ddC 0.375 mg three times daily and followed-up regularly for 48 weeks. RESULTS: The study enrolled 111 patients: 59 men and 52 women, body weight (mean +/- standard deviation) 56.4 +/- 12.3 kg, mean CD4 cell count 324 x 10(6) cells/l, mean HIV RNA 4.7 log10 copies/ml. There were no significant differences between the two groups. Twelve patients discontinued, including two deaths that were unrelated to study medication. No significant differences in adverse events were seen. Week 48 data for the standard dose and half dose arms, respectively, were mean CD4 cell count increases of 52 and 78 x 10(6) cells/l (P = 0.34), mean plasma HIV-1 RNA reduction of 1.4 and 1.1 log10 copies/ml (P = 0.10), HIV RNA of < 400 copies/ml in 52 and 20%[ (P = 0.001). Participants with higher than mean baseline CD8 cell counts (mean 1062 x 10(6) cells/l) showed greater decline in CD8 cells on standard doses. Further analysis showed improved reduction in HIV RNA (P < 0.0001) and in the percentage with undetectable HIV RNA (P = 0.0137) in the standard dose arm, corrected for baseline HIV RNA, which if < 4.75 log10 copies/ml significantly correlated with HIV RNA < 400 copies/ml at week 48. CONCLUSION: At week 48, the proportion with HIV RNA < 400 copies/ml was significantly higher in the standard dose arm; lower baseline HIV RNA correlated with better HIV RNA outcome at 48 weeks. The arms did not differ in CD4 cell response but standard doses correlated with greater CD8 cell decline.

A randomized, dose-finding study with didanosine plus stavudine versus didanosine alone in antiviral-naive, HIV-infected Thai patients.

OBJECTIVES: To evaluate the safety and efficacy of four different regimens of didanosine (ddI) + stavudine (d4T) in HIV-infected Thais. DESIGN: Prospective, open-label, randomized study. METHODS: Patients were randomized to four regimens of high and low doses of ddI and d4T or to ddI alone. D4T was added to the ddI-alone arm after week 24. The duration of study was 48 weeks. RESULTS: Seventy-eight patients were randomized (mean CD4 cell count, 255 x 10(6)/l; mean plasma HIV-1 RNA; 4.3 log10 copies/ml). In the intent-to-treat analysis, 78% of patients in the pooled combination arms and 20% of the patients in the ddI alone arm (to which d4T was added after 24 weeks) showed plasma HIV-1 RNA < 500 copies/ml at week 24 (P < 0.001), and 59% versus 53% at week 48, respectively. In addition, the proportion of patients with < 50 HIV-1 RNA copies/ml was 13% versus 7% at week 24 (P = 0.5) and 17% versus 20% at week 48 respectively. At week 24, median CD4 cell count increases from baseline were 101 x 10(6)/l in the pooled combination versus 76 x 10(6)/l in the ddI alone arm (P = 0.78). Logistic regression modeling suggested a correlation between receiving high dose ddI and achieving HIV-1 RNA < 500 copies/ml at week 48 (P = 0.07). CONCLUSIONS: The d4T/ddI combination was superior to ddI alone in producing HIV-1 viral suppression. At week 48, > 60% of patients treated with this combination reached HIV-1 RNA levels < 500 copies/ml. Receiving high dose ddI but not d4T may correlate with a better viral suppression.

A comparison of two dosing regimens of zidovudine in Thai adults with early symptomatic HIV infection. Conducting clinical HIV trials in South-East Asia.

AIM: To compare the clinical and immunological efficacy, and tolerance of two dosage regimens of zidovudine (ZDV) in an adult Thai population with early symptomatic human immunodeficiency virus (HIV) disease and to identify important clinical issues associated with conducting HIV trials in South-East Asia. METHODS: HIV-infected Thai adults, with early symptomatic HIV disease and CD4 lymphocyte counts less than 400/mm3, who were managed in the infectious diseases clinics at two university teaching hospitals in Bangkok, Thailand, were enrolled in a randomised, open-label, dose-regimen comparison trial of ZDV. Two oral ZDV dosing regimens: regimen A, 100 mg tid+200 mg nocte (ZDV-A) vs regimen B, 250 mg bid (ZDV-B) were compared. The main outcome measures were: 1. Clinical efficacy: rate of progression to acquired immunodeficiency syndrome (AIDS) or death. 2. Immunologic efficacy: changes in CD4 lymphocyte numbers compared to baseline; rate of decline of CD4 lymphocyte numbers to less than 100/mm3. 3. Toxicity, as defined by clinical symptomatology and laboratory parameters. RESULTS: Two hundred and four patients were enrolled (103 ZDV-A; 101 ZDV-B) of whom 195 were followed beyond baseline. Patients were typical of those encountered with HIV in Thailand: mean age 33 years; 89% male; 88% heterosexual HIV acquisition; mean baseline CD4 lymphocyte count 241/mm3. Follow-up while on therapy was comparable for the two groups (mean+/-SD): 533+/-236 days (ZDV-A) vs 592+/-210 days (ZDV-B). One hundred and eleven patients (57%; 51 ZDV-A; 60 ZDV-B) were treated for at least 22 months (669+/-30 days). Clinical and immunological outcomes for ZDV-A and ZDV-B, including rate of progression to AIDS or death, development of non-AIDS-defining opportunistic infections, mean changes in CD4 lymphocyte numbers/mm3, difference in area under the CD4:time distribution curve and difference in the rate of decline of CD4 lymphocyte numbers to less than 100/mm3, were not significantly different. The presence of oral hairy leukoplakia or unintentional weight loss of 10-20% at enrollment were significantly associated with the later development of AIDS (p=0.03 and 0.04, respectively). ZDV-associated toxicity was similar for both regimens. Maintaining protocol adherence and appropriate clinical follow-up emerged as important practical issues. CONCLUSION: In Thai adults, ZDV 100 mg tid+200 mg nocte and ZDV 250 mg bid have similar clinical and immunological efficacy. Rates of ZDV toxicity are comparable to those reported in non-Asian populations. Despite limitations in medical care access and maintaining long-term follow-up, successful trials of antiretroviral agents are feasible in South-East Asia and multi-drug treatment trials should be pursued in appropriate institutions.

A randomized, controlled 24-week study of intermittent subcutaneous interleukin-2 in HIV-1 infected patients in Thailand.

OBJECTIVES: To assess the immunological and virological effects, safety profile and feasibility of subcutaneous interleukin-2 (scIL-2) therapy in an HIV-infected Thai population. DESIGN: Seventy-two patients with baseline CD4 cell count of > or = 350 x 10(6)/l and no history of opportunistic infection were randomized to receive antiretroviral therapy plus scIL-2 (scIL-2 group) or antiretroviral therapy alone (control group). scIL-2 was administered at one of three doses for at least 24 weeks. The main measure of treatment efficacy was change in CD4 cell count. RESULTS: The time-weighted mean change in CD4 cell count from baseline to week 24 was + 252 x 10(6)/l for the scIL-2 group compared with + 42 x 10(6)/l for the control group (P< 0.0001). Changes in plasma HIV RNA were not significantly different between the groups over the same time period: there was a 0.83 log10 copies/ml decrease for the scIL-2 group and a 0.70 log copies/ml decrease for the control group (P= 0.362). CONCLUSIONS: This study provides the most extensive experience of scIL-2 therapy in HIV-1 infected women and Asians, and demonstrates the immunological efficacy, tolerability and feasability of scIL-2 therapy in this population. Data from this study were instrumental in guiding the selection of the scIL-2 dosing regimen for ongoing phase III trials.

Clinical and immunological features of human immunodeficiency virus infection in patients from Bangkok, Thailand.

BACKGROUND: To assess the association between the CD4 count and clinical diseases in a cohort of Thai patients. METHODS: In all, 1902 patients who presented with human immunodeficiency virus (HIV) infection at the Chulalongkorn University Hospital in Bangkok were investigated. RESULTS: At the time of presentation 295 (15.5%) patients had acquired immunodeficiency syndrome (AIDS) and there was a highly significant tendency for lower CD4 counts in this group (median 67/mm3) than in patients free of AIDS (median 369/mm3). A total of 757 patients had data available on follow-up and were free of AIDS at the first visit. During a median follow-up of 0.9 years, 110 developed AIDS or AIDS-related death (12.2/100 person years). Subjects with CD4 count < 200/mm3 at initial visit showed over a ninefold increase in risk of developing AIDS compared to subjects with levels > or = 500/mm3 (relative risk [RR] = 9.1; 95% CI: 5.4-16.0). The rate/100 person years was 47.1 compared with 6.0 in subjects with levels > or = 500/mm3. After adjusting for initial CD4 count, homosexual men showed over a twofold increase in risk of developing AIDS compared to heterosexuals (RR = 2.4; 95% CI: 1.6-4.4) and intravenous drug users (IVDU) showed nearly a twofold increase (RR = 1.8; 95% CI: 0.9-3.9). The increased risk in homosexual men persisted even after further adjustment for clinical stage (RR = 2.2; 95% CI: 1.3-3.7) but the increased risk in IVDU was attenuated (RR = 1.5; 95% CI: 0.7-3.2) although it remained increased albeit non-significantly. Men tended to progress faster to AIDS than women but the difference was not significant. However, the faster progression in homosexual men was seen even when compared to heterosexual men only. CONCLUSION: The rate of progression of AIDS according to CD4 count group at baseline in this Thai cohort is broadly comparable with Western cohorts. It appears that heterosexuals in Thailand show slower progression to AIDS than homosexual men.

PIP: The natural history of HIV infection was investigated in a cohort of 1902 HIV-positive patients (median age, 29 years) seen at the Chulalongkorn University Hospital in Bangkok, Thailand, in 1985-90 in whom a CD4 count was performed at the initial visit. The majority (64%) were male heterosexuals; 10% were homosexual men, 10% reported intravenous drug use, and 16% were heterosexual women. At the time of study enrollment, 295 patients (15.5%) had progressed to AIDS. AIDS patients had a significantly lower CD4 count (median, 67/cu. mm) than those without AIDS (median, 369/cu. mm). Of the 757 patients who were AIDS-free at baseline and available for follow up (median time, 0.9 years), 110 developed AIDS or died from an AIDS-related cause (12.2/100 person-years). Tuberculosis was the major AIDS-defining illness in all risk groups. 50% of those with a CD4 count under 200/cu. mm at the initial visit developed AIDS within 2 years compared with 12% of those with levels of 500/cu. mm (relative risk (RR), 9.1; 95% confidence interval (CI), 5.4-16.0). The rates per 100 person-years were 47.1 and 6.0, respectively. After adjusting for initial CD4 count, homosexual men had a relative risk of developing AIDS of 2.4 (95% CI, 1.6-4.4) compared with heterosexuals; intravenous drug users had a relative risk of 1.8 (95% CI, 0.9-3.9). The increased risk in homosexual men persisted even after further adjustment for clinical stage (relative risk, 2.2; 95% CI, 1.3-3.7), but the increased risk in intravenous drug users was attenuated (RR, 1.5; 95% CI, 0.7-3.2). Older patients progressed faster to AIDS than younger patients, but there was no significant difference between men and women in the course of disease. These findings are consistent with those of studies conducted in Western countries indicating a slower progression to AIDS in heterosexual men than homosexuals and a correlation between CD4 count and rate of progression to AIDS.

International clinical trials of HIV vaccines: I. Phase I trial of an HIV-1 synthetic peptide vaccine in Bangkok, Thailand.

A randomized, double blind, placebo controlled Phase I trial of a prototype human immunodeficiency virus type 1 (HIV-1) synthetic peptide vaccine was conducted in Bangkok, Thailand, to evaluate the safety and immunogenicity of the vaccine in a population of healthy adults at low risk for HIV infection, and to establish essential infrastructure for future HIV vaccine trials in Thailand. Thirty volunteers (25 males; 5 females) were recruited and randomized into 3 groups, receiving 3 intramuscular injections of either 100 micrograms vaccine (N = 12) or 500 micrograms vaccine (N = 12) or alum placebo (N = 6) on weeks 0, 4 and 25. The vaccine was well tolerated without any serious adverse effects. HIV-1 specific ELISA responses were detected in 20/24 subjects who received the vaccine, with V3 binding antibody titers ranging from 1:69 to 1:5,041. HIV-1 (MN) specific neutralizing antibody was detected in 19/20 of subjects with detectable HIV-1 specific binding antibody. Neutralization titers ranged from 1:14 to 1:1,294, which were less than titers observed in HIV-infected subjects. The results of this study indicate that the vaccine was well tolerated, and that the vaccine stimulated anti-HIV humoral immune responses in Thai subjects. The successful undertaking of this first HIV vaccine trial conducted in Thailand provided important preparatory information surrounding volunteer recruitment and motivations, and paves the way for future trials of HIV vaccines in Thailand.

Should travellers in rabies endemic areas receive pre-exposure rabies immunization?

A questionnaire survey was conducted in 1,882 foreign travellers, 74% of which were Europeans, after being in Thailand for an average of 17 days, about the history of potential rabies exposure during their visits. Dog bite and dog lick were experienced in 1.3% and 8.9% of the travellers respectively. The exposed individuals tended to stay in Thailand longer and the incidents occurred mainly in cities rather than in the rural areas. Thirty-one (1.6%) of all travellers had a history of rabies vaccination, 9 as a result of dog bite or dog lick in Thailand whereas the remaining 22 had already received the vaccine prior to coming to Thailand. Such high prevalences of potential rabies exposure and rabies vaccination may justify the inclusion of rabies vaccine into the multiple vaccination program for travellers to rabies endemic countries. This was favoured by over half of the travellers interviewed.

Comparison of the sensitivity of various anti-HIV tests in early seroconversion sera.

Paired sera from 4 patients with proven HIV infection whose initial specimens obtained 14-51 days earlier were indeterminate were simultaneously retested with 7 screening anti-HIV test kits and the immunoblot assay. The study aimed to evaluate the sensitivity of various new and old anti-HIV screening tests. The test kits evaluated were 4 ELISA test kits from Wellcome (Wellcozyme), Organon (Vironostika anti-HTLV-III), Pasteur (Rapid Elavia) and Diagnostic Biotechnology (DB, HIV-1 ELISA), 2 rapid tests based on microfiltration enzyme immunoassay procedure from Rapport (SUDS) and Disease Detection International (SeroCard), and 1 particle agglutination (PA) test (Serodia-HIV). Immunoblot strips from Diagnostic Biotechnology (HIV-1 Western blot) were used to confirm the HIV infection in these serum specimens. Out of the 4 initial serum specimens tested, all were positive by PA, 2 by SUDS, Wellcome and Pasteur, 1 by SeroCard and DB, and none by Organon. When tested by immunoblot, 1 was negative (i.e., completely without any bands) whereas 3 were indeterminate (i.e., 1 with very weak band for p18, 1 with weak band for p24, 1 with very weak band for gp160. All repeat specimens obtained 14-51 days later (mean 32.5 +/- 16 days) were positive by all screening tests as well as immunoblot. Therefore, with these 4 early seroconversion sera, the sensitivity of the PA was 100%, that of SUDS, Wellcome and pasteur was 50%, of that SeroCard and DB was 25%, and Organon, 0%. None of these sera was considered positive by immunoblot.