Two-year safety and tolerability study of enfuvertide use in salvage therapy of Thai HIV-1 experienced cases.

OBJECTIVE: To assess safety and tolerability of enfuvirtide, an antiretroviral, in Thai patients with advanced HIV-1 disease who have received antiretroviral treatment and failed on regimens that contain at least one of each antiretroviral (ARV) classes (PIs, NRTIs, and NNRTIs), or who have intolerance to previous antiretroviral regimens. MATERIAL AND METHOD: An open-label non-comparative study of enfuvirtide used in salvage regimens along with the backbone antiretroviral therapy of choice in Thai HIV-1 experienced cases that have been treated with at least one of each available ARV classes. RESULTS: Twenty-three patients were recruited from five participating centers. Seventeen patients (74%) completed 96 weeks of the treatment. Six patients prematurely withdrew from the present study in which three expired from HIV related complications, two withdrew consents, and one from adverse event. The most common adverse event is injection site reactions, which occurred in 22 patients. The manifestations and intensity varied from rash, erythema, edema, pain, induration, and bleeding at the injection sites, to inflammatory nodules. Most of the patients tolerated the treatment well. Enfuvirtide administered along with other antiretroviral combination provided a good control of the disease. CONCLUSION: Enfuvirtide was well tolerated by Thai patients who participated in the present study. The adverse events did not compromise the patient compliance.

Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents: the recommendations of the Thai AIDS Society (TAS) 2008.

BACKGROUND: More than 100,000 patients have been treated, since the implementation of the National Universal Coverage for antiretroviral therapy (ART) in Thailand Although there are several comprehensive guidelines available internationally, there is a need to have guidelines that can be implemented in Thailand. MATERIAL AND METHOD: The guidelines were developed by a panel of 17 members who are the experts on HIV research and/or HIV patient care and appointed without incentive by the Thai AIDS Society (TAS). The recommendations were based on evidences from the published studies and availability of antiretroviral agents. Published studies that are relevant and applicable to Thailand in particular have been taken into consideration. RESULTS: The recommendations include: when to start ART; what to start; how to monitor the therapy; adverse effects and its management; diagnosis of treatment failure; and antiretroviral treatment options in patients with treatment failure. ART in special circumstances, i.e., patients with co-infection of tuberculosis or hepatitis B virus, is also included Appropriate level of CD4+ T-cell count to start ART among Thai patients has been considered carefully. The authors recommend to start ART at CD4+ T-cell count < 200 cells/mm3. CONCLUSION: ART should be initiated in adults and adolescents HIV-1 infected patients with a history of HIV-related illness or AIDS or with a CD4+ T-cell count <200 cells/mm3. For treatment-naive patients, the preferred initial therapy is a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. CD4' T-cell count and viral load should be monitored for at least twice and once a year, respectively. Proper management of antiretroviral-related toxicity and enhancement of adherence are crucial for the long-term success of ART.

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.

Prevalence of rheumatic disease in HIV infected Thai patients.

OBJECTIVE: To determine the prevalence of rheumatic diseases in HIV-infected patients at Siriraj Hospital, Thailand. MATERIAL AND METHOD: 178 patients who attended the HIV-Clinic at Siriraj Hospital between November 2002 and February 2003 were examined for the presence of rheumatic diseases. Diagnosis of HIV infection was performed by ELISA and confirmed by partial agglutination testing. HIV-infected patients were classified according to the Centers for Disease Control (CDC) 1993 revised classification system. Standard criteria were used to classify the rheumatic diseases. RESULTS: 98 patients had rheumatic diseases. Seventy-seven patients were treated with antiretroviral drugs. Forty-nine patients had mechanical low back pain, twenty-four patients had arthralgia, nineteen patients had plantar fasciitis, eighteen patients had nonspecific myalgia, thirteen patients had fibromyalgia, and eleven patients had others. Arthralgia was associated significantly with Quadricept muscle wasting (p = 0.00001). Nonspecific myalgia was more likely to be associated with female (p = 0. 018) and less likely with use of antiretroviral therapy (p = 0.031). CONCLUSION: Rheumatic diseases were commonly found in HIV-infected patients. Arthralgia associated with wasting Quadricep muscle. Nonspecific myalgia was predominant in female and without antiretroviral drug treatment.

Vaccination against hepatitis B virus: are Thai medical students sufficiently protected?

Medical students are frequently at risk of being infected by hepatitis B virus (HBV) via occupational exposure to infected blood or body fluids. In 2002, the Faculty of Medicine, Siriraj Hospital provided screening tests for HBV serology to all medical students for a vaccination campaign against the infection. There were 1,165 medical students tested. Eight hundred and eleven (69.6%) students had immunity by previous vaccination, but more importantly 212 (18.2%) had no immunity and required vaccination. Most of the students who needed to be vaccinated were in the pre-clinical year (82.5%). Moreover, the students in the pre-clinical year who had previous vaccination had a 2.2 times greater risk of having negative anti-HBs than the students in the clinical year (OR = 2.2, 95% CI = 1.4-3.5). This is because they might have been vaccinated when they were young and the antibody waned overtime.

Estimated economic losses of hospitalized AIDS patients at Siriraj Hospital from January 2003 to December 2003: time for aggressive voluntary counseling and HIV testing.

This retrospective study was performed to explore the pattern of adult HIV-infected patients admitted to Siriraj Hospital from January 2003 to December 2003 and estimated the economic losses of these patients. Two hundred and forty four medical records were available for review. The proportion of male to female was 2 to 1. Mean age of patients was 36.64 +/- 9.72 years. The mean CD4 count among 112 patients was 82.79 +/- 96.49 cell/mm3. One hundred and twenty four (50.82%) were newly diagnosed of HIV infection. The three most common opportunistic infections were Tuberculosis (42.62%), Pneumocystis carinii pneumonia (14.75%), and cryptococcosis (13.11%). The mean duration of admission was 15.72 +/- 15.11 days. The mean expense per admission was 38,194.58 +/- 32,354.86 Baht. Fifty four patients (22.13%) died during admission. The mean income of these patients was 3,903.5 +/- 3,841.42 baht per month. The estimated economic losses of 54 patients who died during admission including medical care expense and income losses due to premature death was 69,769,739.32 baht. However, the expected medical expense of antiretroviral medications in these 54 patients if they had been diagnosed earlier and their lives had been saved would have been 42,214,608 baht. Therefore, vigorous voluntary counseling and HIV testing in patients aged 13-70 years when they have any risk factors for HIV infection regardless of symptoms might be more cost effective than diagnosis when they get sick.

Serological survey of viral hepatitis A, B, and C at Thai Central Region and Bangkok: a population base study.

Hepatitis A, B, and C are important viral hepatitis infections in the Thai population. Hepatitis B vaccination was included in the Thai Expanded Program on Immunization (EPI) 10 years ago. In addition, the seroprevalence of hepatitis A has significantly changed in the last two decades. This study was done to evaluate current risk groups for hepatitis A and B infections and identify the magnitude of hepatitis C infection in the general population of Bangkok and six provinces in the Central Region of Thailand, during the period October 2000 to January 2002. This study revealed that the prevalence of anti-HAV in people younger than 25 years was low but very high in people older than 25 years. The prevalence of anti-HAV was 1.95% in Bangkok and 12.7% in other provinces in people younger than 25 years (p<0.001) while 90.9% in Bangkok and 88.2% in other provinces among people older than 25 years. Therefore, people who are older than 25 years should have a blood test for anti-HAV before getting a hepatitis A vaccination. Approximately 80% of people who are not covered by hepatitis B vaccination from EPI are at risk of hepatitis B infection and its complications. This group of people should receive hepatitis B vaccination. For hepatitis C, the prevalence is lower than 2% across age groups and areas. Therefore, current good primary prevention via blood donor screening and health education must be maintained.

Intracellular production of type I and type II cytokines during HIV-1 progression in Thai patients.

A type I to type II cytokine switch on cells of the immune system has been suggested as a critical step in the etiology of HIV infection. In this study, type I and type II cytokine production of both CD4+ and CD8+ T cells activated by superantigen were investigated in 10 healthy donors and 39 HIV-1 infected patients. Patients were divided into 3 groups based on their CD4 count (< 200, 200-500, > 500 cells/microl). Whole blood from each subject was activated by staphylococcal enterotoxin B (SEB) and anti-CD28. Intracellular cytokine stainings for proinflamatory cytokine (TNF-alpha), type I cytokines (IFN-gamma and IL-2) and type II cytokines (IL-4 and IL-5) in CD4+ and CD8+ T lymphocytes were determined by flow cytometer. Type I cytokine (IFN-gamma) expression in CD4+ T cells co-expressing with CD69 were significantly increased in HIV infected patients, particularly in patients with CD4 counts < 200 and 200-500 cells/microl (means +/- S.D. of 20.7 +/- 18.7% and 10.5 +/- 5.9%, respectively) when compared with 4.8 +/- 1.8% in the normal group (p < 0.05). But IL-2 production in both groups of patients was significantly lower than the normal (3.8 +/- 2.6% and 3.2 +/- 1.4% in patients with < 200, 200-500 cells/microl, and 5.9 +/- 1.5% in the normal group) (p < 0.05). For type II cytokines, there was no difference in all groups of subjects when IL-4 was determined. However, IL-5 production was significantly higher in patients with a CD4 count < 200 cells/microl (0.6 +/- 0.5%) than that in the normal group (0.1 +/- 0.1%) (p < 0.005). CD8+ T cells also showed higher IFN-gamma production in patients with a CD4 count < 200 cells/microl (11.9 +/- 4.7%) and 200-500 cells/microl (12.0 +/- 4.3%) than the normal group (5.3 +/- 2.5%) (p < 0.005). In contrast, IL-2 production in CD8+ T cells was low in these HIV infected patients (0.3 +/- 0.2%, 0.3 +/- 0.2%, and 0.3 +/- 0.4% in patients with < 200, 200-500, and > 500 cells/microl, respectively), which was significantly different compared to the control group (1.2 +/- 0.8%) (p < 0.05). For type II cytokines, only IL-4 production in patients with a CD4 count < 200 cells/microl (0.1 +/- 0.1%) was significantly reduced when compared to the other groups (p < 0.05). This study shows that although HIV infection alters the production of both type I and type II cytokines, it does not induce a polarized type I or type II state in the course of HIV-1 progression in Thai patients.

Safety and efficacy of a simplified fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-VIR) for the treatment of advanced HIV-infected patients: a 24-week study.

OBJECTIVE: To determine the efficacy and safety of the fixed-dose combination of stavudine (d4T), lamivudine (3TC) and nevirapine (NVP) in the treatment of antiretroviral naive HIV-infected Thai adults. PATIENTS AND METHOD: An open-label, single arm trial was conducted Baseline clinical assessment and blood test was done on 10, antiretroviral naive HIV-infected patients, who then received a fixed dose combination of d4T, 3TC and NVP (GPO- VIR, Thai Government Pharmaceutical Organization, Bangkok, Thailand). Nevirapine was given as 200 mg once daily for the first 2 weeks. The patients were followed up at 2, 4, 8, 12 and 24 weeks. A CD4 cell count and HIV-RNA assay were done at 12 and 24 weeks. RESULTS: One hundred and one patients were enrolled The mean baseline CD4 cell count and mean HIV RNA were 58.7 (57.7) cells/mm3 and 5.3 (0.5) log10, copies/mL respectively. At week 24th, the mean decrease in log HIV RNA was 3.6 (0.7) log10 copies/mL [P < 0.001; 95% confidence interval (CI), 2.70-3.03]. Eighty one (80.2%) patients had HIV RNA < 400 copies/mL by intention-to-treat analysis (ITT) and 97.6% had HIV RNA < 400 copies/mL by on-treatment analysis (OT). Sixteen (84.2%) patients with baseline HIV RNA < or = 100,000 copies/mL and 65 (82.3%) patients with baseline HIV RNA > 100,000 copies/mL had viral load < 400 copies/mL by ITT (P = 0.842; 95% CI, -20.9%-16.2%). Sixteen (94.1%) patients with baseline HIV RNA < or = 100,000 copies/mL and 65 (98.5%) patients with baseline HIV RNA > 100,000 copies/mL had viral load < 400 copies/mL by OT (P = 0.295; 95% CI, -25.5%-3.8%). The mean CD4 cell count at week 24 was 155.1 (89.0) cells/mm3 (range 13-402). The mean increase in CD4 cell count from baseline was 96.5 (63.5) cells/ mm3 (P < 0.001). A total of 12% of the patients receiving d4T + 3TC + NVP developed skin rashes. Grade 3 or 4 hepatotoxicity was recognized in 7% of the patients. CONCLUSION: Fixed-dose combination of d4T + 3 TC + NVP (GPO- VIR) is safe, well tolerated and effective in increasing CD4 cell counts and suppression of HIV RNA at 24 weeks in advanced HIV-infected patients in Thailand.

HIV infection/acquired immunodeficiency syndrome at Siriraj Hospital, 2002: time for secondary prevention.

The authors retrospectively reviewed the medical records of HIV/AIDS patients who were admitted to the medical service, Siriraj Hospital from January 1, 2002 through December 31, 2002. Demographics, CD4 lymphocyte counts, discharge diagnoses, the incidence of Pneumocystis carinii pneumonia (PCP), cerebral toxoplasmosis and cryptococcosis in patients who received and did not receive appropriate chemoprophylaxis against those opportunistic infections when indicated, and outcome of the patients were collected. Three hundred medical records of 286 HIV/AIDS patients were available for review. One hundred and seventy two patients (60.1%) were male. Mean age of the patients was 36.8 +/- 9.91 years (range 14-74). The mean CD4 lymphocyte count that was determined in 165 patients was 74.7 +/- 134.21 cells/mm3 (range 0-894). Of the 300 admissions, 36 per cent were newly diagnosed HIV infection. Only 23 (7.7%) patients had received antiretroviral drugs at the time of hospitalization. The leading HIV-related diseases were tuberculosis (29.3%), Pneumocystis carinii pneumonia (18.7%), and cryptococcosis (15.7%). The rest of them included cytomegalovirus diseases (6.3%), lymphoma (6.3%), Salmonella bacteremia (6%), cerebral toxoplasmosis (5.7%), cryptosporidiosis (5.3%), disseminated Mycobacterium avium complex infection (1.0%), extrapulmonary histoplasmosis (1.0%), Candida esophagitis (1.0%), progressive multifocal leukoencephalopathy (1.0%), and rhodococcosis (0.7%). Among those for whom HIV infection was established and chemoprophylaxis for PCP, cerebral toxoplasmosis and cryptococcosis were indicated, 9.8 per cent vs 28.2 per cent, 3.6 per cent vs 5.1 per cent, and 10 per cent vs 15.2 per cent of whom received and did not receive the appropriate chemoprophylaxis developed PCP, cerebral toxoplasmosis and cryptococcosis respectively. One hundred and ninety (63.3%) patients were alive at discharge, 84 (28.0%) had died, 21 (7%) were referred to other hospitals, and 5 (1.7%) left hospital against medical advice. The mortality rate in newly diagnosed HIV and in known HIV without antiretroviral treatment were comparable but much lower in known HIV-infected patients who received antiretroviral therapy. Secondary prevention by detection of HIV-infected patients while they are asymptomatic and providing them with appropriate chemoprophylaxis against specific opportunistic infections as well as appropriate antiretroviral treatment would decrease morbidity, mortality, and improve the quality of life of HIV-infected patients in Thailand.

Infection due to nontuberculous Mycobacterium other than MAC in AIDS patients at Siriraj hospital during 1998-2000: saprophyte vs pathogen.

HIV is a major health problem in Thailand. These patients are vulnerable to opportunistic infections, especially Mycobacterium tuberculosis and MAC infection. However, NTM was considered a rare disease in Thailand before the AIDS era. In this study, there were 38 HIV seropositive patients with NTM (other than MAC) identified from clinical specimens during the 3 year period 1998-2000 at Siriraj Hospital, which has a higher prevalence than the previous report. Among these patients, 29 cases were likely to have had definite infection from NTM, 5 cases possibly had NTM as a pathogen, and 4 cases had NTM as colonization. The most common site of infection was the lung (87%) and most common symptoms were cough (62.2%), fever (34.2%), weight loss (42.1%), and lymphadenopathy (5.3%). The outcome was poor because many NTM are not susceptible to standard medication for tuberculosis which is the empirical treatment for the majority of HIV seropositive patients with a clinical finding suspected of mycobacterial infection. The fatality rate was as high as 58.6 per cent. Awareness of NTM as a potential pathogen in HIV seropositive patientsand adjustment of medications even before the availability of culture results may improve the outcome of treatment of NTM infection in HIV seropositive patients.

Epidemiological correlation between chromium content in gallstones and cholesterol in blood.

The authors measured the chromium in gallstones and bile from patients in three areas (Kawasaki (a city adjacent to Tokyo) in Japan, Chiang Mai and Bangkok in Thailand) by means of neutron activation analysis. The chromium in three types of gallstones (cholesterol, pigment, and rare stones) and bile from patients living in Bangkok were evidently larger than those from patients living in Kawasaki and Chiang Mai. The high chromium intake by Bangkok patients continued from the start of gallstone formation until the time the stones were removed. The total-cholesterol, triglyceride, and hemoglobin A(1C) levels in the blood from Bangkok residents with high chromium intake over a long period were clearly lower than those of Japanese and Chiang Mai residents. The authors showed that the high dietary intake of chromium over a long period may play a role in the lowering of total-cholesterol, triglyceride, and hemoglobin A(1C) in blood.

Increased HIV-DNA load in CCR5-negative lymphocytes without viral phenotypic change.

We have previously described a selective increase in HIV-DNA content in CCR5-negative lymphocytes from late stage HIV-infected patients. Here, we show that this increase occurred even in the absence of viral phenotypic switching from CCR5- to CXCR4-tropic. This leads us to hypothesize that early and late CCR5-tropic viruses might be different in the ability to infect CCR5-low or -negative cells. We compared a set of early CCR5-tropic viruses with low viral DNA content in CCR5-negative cells to a set of late CCR5-tropic viruses with high viral DNA content in CCR5-negative cells. We could not find any significant differences between the two sets of viruses in the aspects of relative infectivity in CCR5-low cells and the level of inhibition by beta-chemokine. This suggested that there may be some changes in cellular phenotype or environment that allows an expansion of susceptible cell population in late stages HIV infection. Understanding these changes may provide a novel approach for HIV therapy.

Studies on the potential use of CD38 expression as a marker for the efficacy of anti-retroviral therapy in HIV-1-infected patients in Thailand.

The monitoring of the efficacy of anti-retroviral therapy (ART) is becoming an important issue in the developing world. The current use of CD4 counts, plasma viral loads, and monitoring of drug-resistant viruses are at present either uninformative or costly. Thus, more new cost-effective and practical techniques need to be established and implemented. Towards this goal, our lab has carried out studies on the potential use of CD38 frequency and density expression by flow analysis as a means to assess the efficacy of ART. Results of our studies using whole blood sample from normal healthy donors indicate that CD38 is expressed by a high frequency of not only CD4+ and CD8+ T cells but also most hematopoietic cell lineages analyzed. Detailed studies of CD38 expression along with other cell surface markers using whole blood sample from HIV-1-infected patients showed that the most discriminating change was the increased frequency and density of CD38 expression by CD3+CD8+ T cells. Of importance was our preliminary finding that a reversal of the increased frequency and density of CD38 expression by CD8+ T cells only appeared in the whole blood sample from patients who were responders to ART but not those who were drug failures. These initial data provide a platform and incentive for larger cohort studies including prospective pre- and post-ART for the institution of such monitoring techniques in resource limited settings.