Surapol Suwanagool

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

ObjectivesTo assess the immunological and virological effects, safety profile and feasibility of subcutaneous interleukin-2 (scIL-2) therapy in an HIV-infected Thai population. DesignSeventy-two patients with baseline CD4 cell count of ⩾ 350 × 106/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. ResultsThe time-weighted mean change in CD4 cell count from baseline to week 24 was + 252 × 106/l for the scIL-2 group compared with + 42 × 106/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). ConclusionsThis 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.

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/μl. 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.

Body Shape and Metabolic Abnormalities in Thai HIV-Infected Patients

Fat and metabolic abnormalities and their associated factors in HIV-infected patients in Thailand were examined. Body fat and fasting lipids (total cholesterol, TC; triglyceride, TG; and HDL-cholesterol, HDL-c) were evaluated in 247 HIV-infected Thais. Body fat was evaluated by subjects and blinded observers, and measured using dual-energy X-ray absorptiometry. Descriptive statistics and logistic regression were used for analyses. Antiretroviral (ARV)-treated Thais were significantly older, more likely to be male, and had higher education and income compared to untreated subjects. The prevalence of lipoatrophy was 10.3% in ARV-naive patients, 36.7% in patients receiving non-protease inhibitor (PI)-based ARV, and 78.7% in PI-based ARV-treated patients (p < 0.001). Excess abdominal or neck fat was found in 0.8%, 6.7%, and 24.6% of the naive, non-PI-treated, and PI-treated, respectively (p < 0.001). Hypercholesterolemia (TC > or = 240 mg/dl) was found in 4.8%, 26.6%, and 42.6%; hypertriglyceridemia (TG > or = 150 mg/dl) in 8.2%, 48.3%, and 75.4%; and low HDL-c (HDL-c < 40 mg/dl) in 42.9%, 20.0%, and 31.2% of the naive, non-PI treated, and PI-treated, respectively (p < 0.05 for all). Central to peripheral fat ratios were 1.11 +/- 0.03, 1.45 +/- 0.06, and 1.93 +/- 0.08 for the naive, non-PI, and PI-treated, respectively (p < 0.001). Treatment was associated with abnormal fat. The adjusted ORs (95% CI) of lipoatrophy for excess fat were 4.6 (2.0-10.7); 6.3 (0.6-71.1) for ARV-naive vs. non-PI; 5.6 (3.4-9.1); 10.7 (3.4-33.8) for ARV-naive vs. PI, and 5.7 (2.4-13.9); 5.3 (1.2-11.4-13.9) for ARV-naive vs. PI. ARV-associated metabolic abnormalities are common in this non-Western population. Appropriate selection and monitoring of ARV treatment are critical to minimize the risk of long-term complications.

Oseltamivir and inhaled zanamivir as influenza prophylaxis in Thai health workers: a randomized, double-blind, placebo-controlled safety trial over 16 weeks

Abstract Objectives Long-term chemoprophylaxis using neuraminidase inhibitors may be needed during influenza epidemics but safety data are limited to several weeks. We sought to assess the tolerability of oseltamivir and zanamivir as primary prophylaxis over 16 weeks. Methods We conducted a parallel group, double blind, 2 (active drug) :1 (placebo) randomized trial of oral oseltamivir/placebo or inhaled zanamivir/placebo over 16 weeks in healthy, Thai hospital professionals at two Bangkok hospitals. The primary endpoint was study withdrawal due to drug-related (possibly, probably, definitely) serious or adverse events (AEs) graded ≥2. Results Recruited subjects numbered 129 oseltamivir/65 placebo and 131 zanamivir/65 placebo. A total of 102 grade ≥2 AEs were reported or detected in 69 subjects: 23/129 (17.8%) versus 15/65 (23.1%) (P = 0.26), and 23/131 (17.6%) versus 8/65 (12.3%) (P = 0.28). Intercurrent infections/fevers [26/102 (25.5%)], abnormal biochemistry [25/102 (24.5%)] and gastrointestinal symptoms [18/102 (17.6%)] were the most frequently reported AEs. There were no drug-related study withdrawals. Eight serious AEs were all due to intercurrent illnesses. Laboratory, lung function and ECG parameters were similar between drugs and placebos. Conclusions Oseltamivir and zanamivir were well tolerated in healthy hospital professionals. Both drugs can be recommended for primary influenza prophylaxis for up to 16 weeks.

Peru-15 (Choleragarde®), a live attenuated oral cholera vaccine, is safe and immunogenic in human immunodeficiency virus (HIV)-seropositive adults in Thailand

BACKGROUND Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccines safety among HIV-seropositive adults had been collected. METHODS This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. RESULTS 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (p<0.001) in the vaccine group compared to 1.6 (p<0.14) in the placebo group. Among the 16 vaccinees,14 vaccinees (87.5%) had seroconversion compared to 1 of 16 placebo recipients (6.3%). V. cholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. CONCLUSION Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults.

Target cell populations of human immunodeficiency virus type 1 in peripheral blood lymphocytes with different chemokine receptors at various stages of disease progression.

ABSTRACT We studied the distribution of human immunodeficiency virus type 1 (HIV-1) DNA in CCR5-positive and -negative peripheral blood lymphocyte populations in HIV-1-infected individuals. While HIV-1 DNA in the CCR5-positive population showed no correlation with CD4 count, the increase of total HIV-1 DNA with lower CD4 count was mainly contributed by the increase of HIV-1 DNA in the CCR5-negative population. This might indicate the change in coreceptor usage from CCR5 to CXCR4 in later stages of disease progression. However, some of the samples with a high viral DNA load in the CCR5-negative population did not have any characteristic of the V3 loop sequence that is compatible with CXCR4 usage or the syncytium-inducing (SI) phenotype. We also did not find any known characteristic change predictive of the SI phenotype in V1 and V2 sequences. Our findings showed that there might be a shift in target cell populations during disease progression, and this shift was not necessarily associated with the genetic changes characteristic of CXCR4 usage.