Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2014, Thailand.

New evidence has emerged regarding when to commence antiretroviral therapy (ART), optimal treatment regimens, management of HIV co-infection with opportunistic infections, and management of ART failure. The 2014 guidelines were developed by the collaborations of the Department of Disease Control, Ministry of Public Health (MOPH) and the Thai AIDS Society (TAS). One of the major changes in the guidelines included recommending to initiating ART irrespective of CD4 cell count. However, it is with an emphasis that commencing HAART at CD4 cell count above 500 cell/mm(3) is for public health, in term of preventing HIV transmission and personal benefit. In tuberculosis co-infected patients with CD4 cell counts ≤50 cells/mm(3) or with CD4 cell counts >50 cells/mm(3) who have severe clinical disease, ART should be initiated within 2 weeks of starting tuberculosis treatment. The preferred initial ART regimen in treatment naïve patients is efavirenz combined with tenofovir and emtricitabine or lamivudine. Plasma HIV viral load assessment should be done twice a year until achieving undetectable results; and will then be monitored once a year. CD4 cell count should be monitored every 6 months until CD4 cell count ≥350 cells/mm(3) and with plasma HIV viral load <50 copies/mL; then it should be monitored once a year afterward. HIV drug resistance genotypic test is indicated when plasma HIV viral load >1,000 copies/mL while on ART. Ritonavir-boosted lopinavir or atazanavir in combination with optimized two nucleoside-analogue reverse transcriptase inhibitors is recommended after initial ART regimen failure. Long-term ART-related safety monitoring has also been included in the guidelines.

Etiology and risk factors of stroke in HIV-infected patients in Siriraj Hospital: a case-control study.

BACKGROUND: Stroke and HIV infection are major health problems in Thailand. There is limited data regarding the etiology and risk factors of stroke in HIV-infected Thai patients. OBJECTIVE: To study the risk factors, types, and mechanisms of stroke in HIV-infected patients. MATERIAL AND METHOD: The authors reviewed records of consecutive HIV-infected patients with acute first stroke in a large urban medical center from August 1, 2009 through December 31, 2010. Age-matched controls of HIV-infected patients without stroke were consecutively recruited at a 2:1 ratio. Data collection included demographics, stroke subtypes, risk factors of stroke, and HIV disease parameters. Multiple logistic regression analysis (p < 0.05) identified factors associated with stroke in HIV-infected patients. RESULTS: There were 37 subjects and 74 controls. In HIV-positive stroke patients, 81.1% were males and mean age was 50.5 years. There were 33 and 4 cases of ischemic and hemorrhagic strokes respectively. HIV infection was previously diagnosed in 70%, mean CD4 count was 287 cells/uL and 33% had CD4 counts < 200 cells/uL. Prior antiretroviral medications were used in 49%. TOAST classification of stroke was as follows: large artery atherosclerosis 2 (6.1%), small vessel occlusion 9 (27.3%), cardioembolism 2 (6.1%), other determined etiology 9 (27.3%) (vertebral artery dissection 1, anti-thrombin III deficiency 1, thrombotic thrombocytopenic purpura 1, tuberculous meningitis 4, cryptococcal meningitis 1, intravenous heroin 1) and undetermined 11 (33.2%) (incomplete evaluation 10, negative evaluation 1). Multivariate analysis demonstrated the following to be significant risk factors of stroke: smoking p = 0.001, adjusted OR 6.9 (95% CI 12.3, 21.1) and tuberculous meningitis p = 0.034, adjusted OR 11.9 (95% CI 1.2, 117.2). CONCLUSION: Stroke etiology in HIV-infected patients is more heterogeneous than in non-immunocompromised hosts. Smoking and concurrent tuberculous meningitis were significantly associated with stroke in HIV-infected Thai patients. Further prospective cohort studies should be performed in a larger population of more severely immunocompromised patients in Thailand.

Effect of radiation therapy to immunological and virological status in HIV/AIDS-cancer patients, preliminary report.

OBJECTIVE: To describe effects of radiation therapy (RT) on immunological status (CD4 cell counts) and disease progression among HIV-positive cancer patients. MATERIAL AND METHOD: This prospective observational study was conducted among HIV-positive cancer patients who received RT for curative intention of cancer in five selected hospitals in Thailand. All subjects received external beam radiation therapy, according to standard clinical practice guidelines of RT. Blood samples were taken 4 times for complete blood count, CD4 cell count and plasma HIV RNA viral load (HIV-VL) assays before and in the last week of RT, then three and six months after completion of RT. RESULTS: This preliminary study reported immunological status and HIV-VL before and the last week of RT, among 29 HIV-positive female cancer patients enrolled from August 22, 2009 to June 30, 2010. The median age was 38 years (range 30-54). 27 patients (93 percent) had invasive cervical cancer. 26 patients (90 percent) were on antiretroviral treatment (ART). The mean baseline white blood cell (WBC) count, lymphocyte percentage were 6,771.7 cells/microL and 31.7 percent respectively. The mean baseline CD4 cell count and CD4%, 387.8 cells/microL and 17.5 percent respectively. In the last week of RT, 25 subjects (86 percent) had CD4 count less than 200 cells/microL. The last week, mean WBC count, and mean lymphocyte percentage decreased to 3,902.8 cells/microL and 17.5 percent respectively. Mean CD4 count number decreased to 157.7 cells/microL, but the mean CD4 % did not change. Four patients (14 percent) had increased HIV-VL after RT, of these two were not on ART and two were on ART for more than 1 year. CONCLUSION: The CD4 cell count was not a good surrogate for prediction of immunologic status of HIV-positive cancer patients during RT.

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.

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

BACKGROUND: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. METHODS AND FINDINGS: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. CONCLUSIONS: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.

Cryptococcal immune reconstitution inflammatory syndrome after antiretroviral therapy in AIDS patients with cryptococcal meningitis: a prospective multicenter study.

A prospective multicenter study of cryptococcal immune reconstitution inflammatory syndrome (IRIS) was conducted as a substudy of the Bacteriology and Mycology Study Group 3-01. Of 101 AIDS patients with cryptococcal meningitis who received highly active antiretroviral therapy (HAART), 13 experienced cryptococcal IRIS. No association between the timing of HAART initiation and the diagnosis of IRIS was identified. Increased baseline serum cryptococcal antigen (CrAg) titer was a risk factor for cryptococcal IRIS.

Causes of death in HIV-infected persons who have tuberculosis, Thailand.

Up to 50% of persons with HIV and a diagnosis of tuberculosis (TB) in Thailand die during TB treatment. In a prospective observational study, a team of physicians ascribed the cause of death after reviewing verbal autopsies (interviews of family members about events preceding death), laboratory data, and medical records. Of 849 HIV-infected TB patients enrolled, 142 (17%) died. The cause of death was TB for 38 (27%), including 6 with multidrug-resistant TB and 20 with disseminated TB; an HIV-associated condition other than TB for 50 (35%); and a condition unrelated to TB or HIV for 22 (15%). Twenty-three patients (16%) were judged not to have had TB at all. Death from all causes except those unrelated to TB or HIV was less common in persons receiving antiretroviral therapy (ART). In addition to increasing the use of ART, death rates may be reduced through expanded use of modern TB diagnostic techniques.

Diagnostic accuracy of perfusion CT in differentiating brain abscess from necrotic tumor.

OBJECTIVE: To evaluate the diagnostic accuracy of perfusion computed tomography (CTP) in differentiating between brain abscess and necrotic tumor. MATERIAL AND METHOD: Prospective study was performed in patients suspected of a space taking lesion in the brain. CTP was done at the suspected levels and post-processing measurement of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability surface index (PS) were evaluated at ring enhanced area, central non-enhanced area, edema and contralateral normal brain. RESULTS: Seventeen patients with 21 lesions were studied. Of the 21 lesions, 12 were abscess and nine were tumors. By comparing means, only MTT at the ring enhanced area showed statistically significant difference between brain abscess and tumor (p = 0.009, 95% CI = 1.403 to 4.900). When ratio of CBV, CBF and MTT of the ring enhanced area and contralateral normal brain were analyzed (CBVr, CBFr, MTTr respectively), there were significant differences of CBVr and CBFr between the two groups (p = 0.003, 95% CI = -4.266 to -1.051 and p = 0.006, 95% CI = -9.934 to -1.969 respectively). With the threshold of CBVr more than or equal to 1.5 and CBFr more than or equal to 1, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis of tumor were 100%, 75%, 75%, 100%, and 85.7% respectively. CONCLUSION: The CTP was shown to be useful in differentiating brain abscess from tumor. With CBVr less than 1.5, tumor can be excluded.

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.

Implementation and assessment of a prevention with positives intervention among people living with HIV at five hospitals in Thailand.

BACKGROUND: We implemented a hospital-based prevention with positives (PwP) intervention among people living with HIV (PLHIV) that included HIV transmission risk screening, short HIV prevention messages, family planning, HIV disclosure counseling, and partner HIV testing at five hospitals in Thailand. We assessed changes in sexual risk behaviors among PLHIV who received the PwP services at the hospitals. METHODS: From January 2008-March 2009, we systematically selected a subset of PLHIV receiving care at the five hospitals to offer participation in the PwP intervention. We collected demographic, risk behavior, and laboratory data using a standardized questionnaire. We analyzed data from PLHIV who completed at least four visits, using generalized estimating equations to identify baseline participant characteristics that were associated with adopting sexual practices less likely to be associated with HIV transmission during follow-up. RESULTS: A total of 830 PLHIV were interviewed and 756 (91.1%) completed four visits. The median age of these 756 participants was 37 years, 400 (52.9%) were women, and 475 (62.8%) had a steady partner. At baseline, 353 (74.3%) of the steady partners had been tested for HIV and 132 (37.4%) had tested negative. Among the 756 PLHIV, 427 (56.5%) reported having sex in the 3 months before enrollment and 413 (54.6%) in the 3 months before the fourth visit. The proportion reporting having vaginal or anal sex without a condom decreased from 20.8% at baseline to 5.1% at the fourth visit (p<0.001). Factors associated (p<0.05) with abstinence or 100% condom use at follow-up visits included: completing ≥ two visits, being diagnosed with HIV for longer than 3 months, and receiving HIV prevention messages from a doctor (versus a nurse or counselor). CONCLUSION: Safe sex behaviors increased among PLHIV receiving PwP services, suggesting that expansion of hospital-based PwP services may reduce the number of new HIV infections in Thailand.

High rate multiple drug resistances in HIV-infected patients failing nonnucleoside reverse transcriptase inhibitor regimens in Thailand, where subtype A/E is predominant.

The prevalence of drug resistance was determined among 64 HIV-infected Thai patients who were failed while receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. Eighty-nine percent of patients had 1 or more NNRTI mutation resistances. Almost all patients had resistance to at least 1 nucleoside reverse transcriptase inhibitor (NRTI), and 42% had multiple-NRTI resistance.

Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate in Asian Subjects with Human Immunodeficiency Virus 1 Infection: A Sub-Analysis of Phase 3 Clinical Trials.

The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) were analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naïve and ART-experienced Asian subjects infected with human immunodeficiency virus (HIV)-1. Studies GS-US-236-102 and GS-US-236-103 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naïve subjects, comparing E/C/F/TDF versus efavirenz (EFV)/F/TDF or ritonavir-boosted atazanavir (ATV+RTV) plus emtricitabine/tenofovir DF (F/TDF), respectively. Studies GS-US-236-115 and GS-US-236-121 were randomized, open-label, 96-week long conducted in ART-experienced subjects, who switched to E/C/F/TDF from ritonavir-boosted protease inhibitors (PI+RTV)+F/TDF, or non-nucleoside reverse transcriptase inhibitors (NNRTI)+F/TDF regimens. The E/C/F/TDF appeared to have sustained efficacy and safety and was well tolerated in the small number of ART-naïve and ART-experienced Asian subjects.

The burden of HIV-associated neurocognitive disorder (HAND) in the Asia-Pacific region and recommendations for screening.

BACKGROUND: HIV-associated neurocognitive disorder incurs a significant burden on HIV patients in Asia-Pacific countries; however, the incidence is difficult to estimate due to a lack of local epidemiological data. The impact of neurocognitive impairment in HIV patients is often underestimated due to a lack of education and awareness, and there are consequently gaps in the provision of screening and diagnosis to enable earlier intervention to limit neurocognitive impairment. METHOD: This review seeks to redress the imbalance by promoting awareness and education among physicians concerning the neurovirulence of HIV and thereby increase screening efforts to improve diagnosis rates and clinical outcomes for underserved patients in this region. The Asia, Australia, and Middle East (AAME) HAND Advisory Board convened expert regional representatives to review current practice and recommend appropriate measures related to the implementation of standardised screening programmes and treatment recommendations to curb the developing HAND epidemic in the region. In particular, we recommend basic neuropsychological testing protocols that could be efficiently introduced into clinical practice for routine screening. RESULT: We also propose simple guidelines for the management of HAND. We believe that HAND is a significant and under-reported diagnosis in HIV patients that warrants both greater recognition and further clinical investigation of the underlying pathophysiology and the impact of HIV disease progression, with HAND being associated with worse medication adherence and therefore possibly increased risk of ARV treatment failure. DISCUSSION: Widespread screening will lead to greater recognition of HAND and earlier intervention, which may lead to improved management strategies in the future.

Nevirapine plasma concentrations and concomitant use of rifampin in patients coinfected with HIV-1 and tuberculosis.

OBJECTIVES: In countries with high numbers of HIV/tuberculosis coinfection nevirapine and rifampin are used extensively. However, limited data are available about whether or not nevirapine and rifampin can be safely coadministered without the plasma concentration of nevirapine falling below therapeutic levels. METHODS: Blood samples for determination of nevirapine plasma concentrations were collected from patients using nevirapine 200 mg twice daily with or without concomitant rifampin. Bivariate and multivariate linear regression models were used to investigate factors possibly related to nevirapine concentrations. RESULTS: We received 74 blood samples from patients using nevirapine plus rifampin, and collected blood samples from an equal number of controls using nevirapine only. Groups were similar for age, gender, weight, height and body mass index (BMI). In the rifampin group the mean nevirapine concentration was 5.47 +/- 2.66 mg/l, whereas in the control group the mean nevirapine concentration was 8.72 +/- 3.98 mg/l. In the rifampin group seven nevirapine trough concentrations were low (< 3.1 mg/l), while in the control group two patients had low nevirapine trough concentrations (P = 0.164). In the multivariate linear regression analysis, corrected for time after drug intake, the use of rifampin was significantly (P < 0.001) associated with lower nevirapine plasma concentrations, whereas higher BMI reached borderline significance (P = 0.065). CONCLUSION: Although nevirapine plasma concentrations were 3.3 mg/l lower when co-administered with rifampin, still more than 86% of these patients had nevirapine plasma concentrations > 3.1 mg/l. Our results suggest that from a pharmacological point of view the majority of Thai coinfected patients, who have low BMIs, reach nevirapine plasma concentrations that are adequate for treatment of HIV. However this can only be undertaken if nevirapine plasma concentration monitoring is available and can be closely followed.

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.

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.

Utility of Cryptococcal Antigen Screening and Evolution of Asymptomatic Cryptococcal Antigenemia among HIV-Infected Women Starting Antiretroviral Therapy in Thailand.

Cryptococcal meningitis (CM) remains a significant HIV-associated opportunistic infection in Southeast Asia and Africa, with a high burden of disease and a high mortality rate despite the availability of antiretroviral therapy (ART). We retrospectively examined the utility of cryptococcal antigen screening to identify risk for CM among 211 Thai women initiating ART. Antigenemia prevalence was 11% (n = 9) among 84 women with a CD4 count <100 cells/mm(3). Screening identified all women who later developed CM. Cryptococcal antigen titers decreased over time with ART. Our study confirmed findings from previous studies in Thailand and South Africa and provided novel observational data regarding the course of cryptococcal antigenemia in patients initiating ART and the poor efficacy of low-dose fluconazole prophylaxis in preventing CM among patients with antigenemia.