Coreceptor tropism determined by genotypic assay in HIV-1 circulating in Thailand, where CRF01_AE predominates.

OBJECTIVES: Chemokine (C-C motif) receptor 5 (CCR5) inhibitors are a novel class of antiretroviral agents that are promising for treatment of patients who harbour the HIV-1 R5 strain. Data on coreceptor tropism in non-B HIV-1 subtypes are limited. We studied coreceptor tropism in HIV-1 circulating in Thailand, where CRF01_AE predominates, using a genotypic assay. METHODS: We compiled V3 sequences of HIV-1 strains circulating in Thailand during 2010-2012. Coreceptor tropism was predicted based on V3 sequences using geno2pheno version 2.5 (http://coreceptor.bioinf.mpi-inf.mpg.de). RESULTS: One hundred and fifty-five HIV-1-infected patients were enrolled in this study. Ninety-nine patients (63.9%) were antiretroviral-naïve, and the remainder had virological failure. The median (interquartile range) CD4 cell count and HIV-1 RNA were 220 (74-379) cells/µL and 75,374 (14,127-226,686) HIV-1 RNA copies/mL, respectively. Of the sequences obtained from these patients, 119 (76.8%) were CRF01_AE and 22 (14.2%) were subtype B. At a false positive rate of < 5%, 61 (39.4%) HIV-1-infected individuals were predicted to harbour the X4 phenotype. X4 viruses were detected more frequently in the treatment-failure group compared with the treatment-naïve group (30.3 vs. 55.4%, respectively; P = 0.002). Those with CRF01_AE had a higher proportion of X4 viruses compared with non-AE subtypes (47.9 vs. 11.1%, respectively; P < 0.001). By multivariate logistic regression, CRF01_AE and treatment failure were independently associated with predicted X4 phenotype [odds ratio (OR) 7.93; 95% confidence interval (CI) 2.57-24.50; P < 0.001, and OR 3.10; 95% CI 1.50-6.42; P = 0.002, respectively]. CONCLUSIONS: CRF01_AE and treatment failure are associated with the predicted X4 phenotype. In regions where CRF01_AE predominates, use of CCR5 inhibitors must be considered with caution. The phenotypic assay and its correlation with genotypes should be further investigated in CRF01_AE.

Low level of efavirenz in HIV-1-infected Thai adults is associated with the CYP2B6 polymorphism.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) infections with a plasma efavirenz concentration of <1,000 ng/mL appear to have a high risk for the emergence of drug resistance. In the present study, we assessed the influence of the CYP2B6 polymorphism on the plasma efavirenz level. METHODS: CYP2B6 T18492C (rs2279345) in 149 HIV-infected Thai adults were genotyped. Plasma efavirenz concentrations 12 h after dosing were measured using a validated high-performance liquid chromatography. The relationship between the plasma efavirenz level and the CYP2B6 T18492C polymorphism were analysed. RESULTS: Among the 149 patients, the frequency of T18492C heterozygous (T/C) and homozygous mutant (C/C) was 38.26 % (n = 57) and 6.04 % (n = 9), respectively. In the entire cohort, the median efavirenz plasma concentration was 2,410 ng/mL [interquartile range (IQR) 1,460-4,120 ng/mL]. The plasma efavirenz concentration for patients with 18492CC (1,200 ng/mL, IQR 1,050-1,990 ng/mL) or 18492TC (1,900 ng/mL, IQR 1,320-2,510 ng/mL) genotypes were significantly lower than those with homozygous wild type (3,380 ng/mL, IQR 2,040-5,660 ng/mL), P-value < 0.001. CONCLUSIONS: The CYP2B6 T18492C polymorphism was significantly associated with lower efavirenz concentrations compared to those with homozygous wild type in HIV-1 infections. The genetic polymorphism CYP2B6 T18492C may be useful for the optimised efavirenz dose. Further studies in the clinical setting will need to be conducted before such an approach can be recommended for widespread use.

Development of multiplex pyrosequencing for HLA-B*57:01 screening using single nucleotide polymorphism haplotype.

WHAT IS KNOWN AND OBJECTIVE: Abacavir (ABC) is a commonly used nucleoside reverse-transcriptase inhibitor with potent antiviral activity against HIV-1. The US Food and Drug Administration and international HIV treatment guidelines recommend HLA-B*57:01 screening before initiating treatment with ABC. The current standard method for HLA-B*57:01 screening is limited by its high-cost, time-consuming and labour-intensive procedure with the requirement of a specialized laboratory. Our study aims to develop a more reliable screening test by selecting rs3093726 as an additional single nucleotide polymorphism (SNP) to combine with rs2395029 for multiplex pyrosequencing development. It offers high-accuracy, cost-effective and rapid detection. METHODS: Multiplex pyrosequencing was developed for HLA-B*57:01 screening using rs2395029 and rs3093726 as a surrogate marker and tested in 130 Thai subjects in parallel with singleplex pyrosequencing of each SNP and the standard sequence-based method. RESULTS AND DISCUSSION: Multiplex pyrosequencing showed 100% concordance when compared with both singleplex pyrosequencing and standard sequence-based method. This method showed 100% of negative predictive value (NPV), positive predictive value (PPV), specificity and sensitivity. WHAT IS NEW AND CONCLUSION: Multiplex pyrosequencing is a powerful tool for HLA-B*57:01 screening using the rs2395029 and rs3093726 haplotype genotyping as surrogate marker for this HLA-B. The assay provides accurate, cost-effective and rapid detection of this haplotype. It can be applied for ABC hypersensitivity screening of the Thai population before initiating treatment with ABC.

Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study.

OBJECTIVES: Amid the increasing number of pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19. METHODS: From 27 March to 4 April 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared. RESULTS: Two-hundred pairs of samples were collected. Sixty-nine (34.5%) individuals were male, and the median (interquartile) age was 36 (28-48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% (95% CI 60.4%-96.6%), and 98.9% (95% CI 96.1%-99.9%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (κ coefficient 0.851, 95% CI 0.723-0.979; p < 0.001). CONCLUSIONS: Saliva might be an alternative specimen for the diagnosis of COVID-19. The collection is non-invasive, and non-aerosol generating. This method could facilitate the diagnosis of the disease, given the simplicity of specimen collection and good diagnostic performance.

Monitoring and impact of fluconazole serum and cerebrospinal fluid concentration in HIV-associated cryptococcal meningitis-infected patients.

OBJECTIVES: The aim of the present study was to assess fluconazole pharmacokinetic measures in serum and cerebrospinal fluid (CSF); and the correlation of these measures with clinical outcomes of invasive fungal infections. METHODS: A randomized trial was conducted in HIV-infected patients receiving three different regimens of fluconazole plus amphotericin B (AmB) for the treatment of cryptococcal meningitis. Regimens included fluconazole 400 mg/day+AmB (AmB+Fluc400) or fluconazole 800 mg/day+AmB (AmB+Fluc800) (14 days followed by fluconazole alone at the randomized dose for 56 days); or AmB alone for 14 days followed by fluconazole 400 mg/day for 56 days. Serum (at 24 h after dosing) and CSF samples were taken at baseline and days 14 and 70 (serum only) for fluconazole measurement, using gas-liquid chromatography. RESULTS: Sixty-four treated patients had fluconazole measurements: 11 in the AmB group, 12 in the AmB+Fluc400 group and 41 in the AmB+Fluc800 group. Day 14 serum concentration geometric means were 24.7 mg/L for AmB+Fluc400 and 37.0 mg/L for AmB+Fluc800. Correspondingly, CSF concentration geometric means were 25.1 mg/L and 32.7 mg/L. Day 14 Serum and CSF concentrations were highly correlated with AmB+Fluc800 (P<0.001, r=0.873) and AmB+Fluc400 (P=0.005, r=0.943). Increased serum area under the curve (AUC) appears to be associated with decreased mortality at day 70 (P=0.061, odds ratio=2.19) as well as with increased study composite endpoint success at days 42 and 70 (P=0.081, odds ratio=2.25 and 0.058, 2.89, respectively). CONCLUSION: High fluconazole dosage (800 mg/day) for the treatment of HIV-associated cryptococcal meningitis was associated with high serum and CSF fluconazole concentration. Overall, high serum and CSF concentration appear to be associated with increased survival and primary composite endpoint success.

Deferred modification of antiretroviral regimen following documented treatment failure in Asia: results from the TREAT Asia HIV Observational Database (TAHOD).

OBJECTIVE: The aim of the study was to examine the rates and predictors of treatment modification following combination antiretroviral therapy (cART) failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational Database (TAHOD). METHODS: Treatment failure (immunological, virological and clinical) was defined by World Health Organization criteria. Countries were categorized as high or low income by World Bank criteria. RESULTS: Among 2446 patients who initiated cART, 447 were documented to have developed treatment failure over 5697 person-years (7.8 per 100 person-years). A total of 253 patients changed at least one drug after failure (51.6 per 100 person-years). There was no difference between patients from high- and low-income countries [adjusted hazard ratio (HR) 1.02; P=0.891]. Advanced disease stage [Centers for Disease Control and Prevention (CDC) category C vs. A; adjusted HR 1.38, P=0.040], a lower CD4 count (>or=51 cells/microL vs. or=400 HIV-1 RNA copies/mL vs. <400 copies/mL; adjusted HR 2.69, P<0.001) were associated with a higher rate of treatment modification after failure. Compared with patients from low-income countries, patients from high-income countries were more likely to change two or more drugs (67%vs. 49%; P=0.009) and to change to a protease-inhibitor-containing regimen (48%vs. 16%; P<0.001). CONCLUSIONS: In a cohort of Asian patients with HIV infection, nearly half remained on the failing regimen in the first year following documented treatment failure. This deferred modification is likely to have negative implications for accumulation of drug resistance and response to second-line treatment. There is a need to scale up the availability of second-line regimens and virological monitoring in this region.

Measures of site resourcing predict virologic suppression, immunologic response and HIV disease progression following highly active antiretroviral therapy (HAART) in the TREAT Asia HIV Observational Database (TAHOD).

OBJECTIVES: Surrogate markers of HIV disease progression are HIV RNA in plasma viral load (VL) and CD4 cell count (immune function). Despite improved international access to antiretrovirals, surrogate marker diagnostics are not routinely available in resource-limited settings. Therefore, the objective was to assess effects of economic and diagnostic resourcing on patient treatment outcomes. METHODS: Analyses were based on 2333 patients initiating highly active antiretroviral therapy (HAART) from 2000 onwards. Sites were categorized by World Bank country income criteria (high/low) and annual frequency of VL (> or = 3, 1-2 or <1) or CD4 (> or = 3 or <3) testing. Endpoints were time to AIDS/death and change in CD4 cell count and VL suppression (<400 HIV-1 RNA copies/mL) at 12 months. Demographics, Centers for Disease Control and Prevention (CDC) classification, baseline VL/CD4 cell counts, hepatitis B/C coinfections and HAART regimen were covariates. Time to AIDS/death was analysed by proportional hazards models. CD4 and VL endpoints were analysed using linear and logistic regression, respectively. RESULTS: Increased disease progression was associated with site-reported VL testing less than once per year [hazard ratio (HR)=1.4; P=0.032], severely symptomatic HIV infection (HR=1.4; P=0.003) and hepatitis C virus coinfection (HR=1.8; P=0.011). A total of 1120 patients (48.2%) had change in CD4 cell count data. Smaller increases were associated with older age (P<0.001) and 'Other' HIV source exposures, including injecting drug use and blood products (P=0.043). A total of 785 patients (33.7%) contributed to the VL suppression analyses. Patients from sites with VL testing less than once per year [odds ratio (OR)=0.30; P<0.001] and reporting 'Other' HIV exposures experienced reduced suppression (OR=0.28; P<0.001). CONCLUSION: Low measures of site resourcing were associated with less favourable patient outcomes, including a 35% increase in disease progression in patients from sites with VL testing less than once per year.

Predicting factors for unsuccessful switching from nevirapine to efavirenz in HIV-infected patients who developed nevirapine-associated skin rash.

Skin rash associated with nevirapine (NVP) is common and efavirenz (EFV) is often used as a substitute. We aimed to determine the predicting factors for unsuccessful switching from NVP to EFV. A retrospective cohort study was conducted in HIV-infected patients who developed rash after taking NVP. There were 109 patients with a mean standard deviation (SD) age of 36.6 (7.4) years and 45% were males. Median (interquartile range) CD4 cell count and HIV RNA at the time of NVP initiation were 163 (50-273) cells/mm(3) and 4.6 (1.7-5.4) log copies/mL, respectively. Twenty (18.3%) patients subsequently developed EFV-associated rash. By logistic regression, history of drug allergy apart from NVP (odds ratio [OR] 11.42) and CD4 cell count <100 cells/mm(3) (OR 6.14) were significant predicting factors for EFV-associated rash. Two predicting factors for unsuccessful switching from NVP to EFV were found. Patients who have these factors need to have a close follow-up if EFV is substituted.

Impact of drug-resistant tuberculosis on the survival of HIV-infected patients.

OBJECTIVE: To determine the effect of drug-resistant tuberculosis (TB) on the survival of human immunodeficiency virus (HIV) infected patients in an area with a high prevalence of TB. DESIGN: Retrospective cohort study. RESULTS: Of 225 HIV-TB patients with a mean age of 35.8 years, 72.4% were male. The median CD4 cell count at TB diagnosis was 44 cells/mm3. Sixty per cent presented with extra-pulmonary TB (EPTB). Sixty-three (28%) patients were infected with Mycobacterium tuberculosis resistant to at least one drug; respectively 16.4%, 9.3%, 5.3% and 12.9% were resistant to isoniazid (INH), rifampicin (RMP), ethambutol and streptomycin, and 14 (6.2%) had multidrug-resistant TB (MDR-TB). During a median follow-up of 11.5 months, 4% died. From Kaplan-Meier analysis, INH resistance, RMP resistance and MDR-TB were associated with shorter survival (log-rank test, P < 0.005). Cox's proportional hazard model showed that MDR-TB (hazard ratio [HR] 11.7; 95% CI 2.1-64.9), not receiving antiretroviral therapy (ART) (HR 7.9; 95% CI 1.5-43.1) and EPTB (HR 5.1; 95% CI 1.9-25.9) were significant risk factors for death. CONCLUSION: MDR-TB and EPTB substantially reduce survival among patients co-infected with HIV and TB. Early detection and optimal treatment of MDR-TB are crucial. ART significantly prolongs survival and should be initiated in HIV-TB co-infected patients.

Clinical presentation and medical complication in 59 cases of laboratory-confirmed leptospirosis in Bangkok.

We reviewed the laboratory-confirmed cases of leptospirosis in Ramathibodi Hospital, a medical-school hospital in Bangkok, to assess the documented cases of leptospirosis in Bangkok and the medical complications of severe cases. There were 59 cases from January 1994 to December 2000. More than half of the cases were Bangkok residents and did not travel outside Bangkok in the preceding 2 weeks. The majority of the cases presented in late rainy season. The clinical presentation, laboratory findings, medical complication, treatment and outcome are given. Leptospirosis in the urban area is common and should be recognized, particularly in rainy season.

Pneumocystis carinii pneumonia in patients without HIV infection.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) can occur in immunocompromised patients without HIV infection. Risk factors, clinical features, treatment outcomes, and factors related to mortality in these patients may be useful clinical data for physicians who care for these patients. METHOD: A retrospective study of PCP patients without HIV infection at Ramathibodi Hospital, from 1994 to 2001, was conducted. Only cases with microbiological and/or pathological proven were included. RESULTS: There were 19 patients with 42.1 per cent males and a mean age of 44.6 years. All patients had underlying immunocompromised diseases. 94.7 per cent of the cases received immunosuppressive drugs. PCP occurred at a mean duration of 26.4 months after the diagnosis and treatment of underlying diseases. Common clinical presentations of PCP were progressive dyspnea, fever, and non-productive cough. All patients had abnormal chest radiography with a majority of bilateral interstitial infiltration (63.2%). Diagnosis of PCP was confirmed with microbiological examination from bronchoalveolar larvage (84.2%) and pathological diagnosis from transbronchial biopsy (15.8%). Almost all of the cases (94.7%) were treated with co-trimoxazole. Ten patients (52.6%) had concomitant bacterial pneumonia or fungal pneumonitis. Overall mortality rate was 36.8 per cent. Mortality was significantly higher in patients who needed mechanical ventilation (p = 0.006). There was a trend toward a higher mortality rate in patients with concomitant pulmonary diseases (p = 0.09). CONCLUSIONS: PCP may complicate a variety of immunocompromised states especially autoimmune diseases and hematologic malignancy. Patients who receive corticosteroids and/or cytotoxic drugs should receive primary PCP prophylaxis. The mortality rate is high especially in severe cases that need mechanical ventilation. Intensive care and close monitoring are needed for these patients.

Treatment of invasive fungal sinusitis with liposomal amphotericin B: a report of four cases.

Invasive fungal sinusitis increasingly causes significant morbidity and mortality in immunocompromised patients. It is difficult to treat. Despite standard treatment by surgical debridement and intravenous amphotericin B, morbidity and mortality remain high. Conventional amphotericin B is the standard drug but its use is limited by dose-related nephrotoxicity and infusion-related acute toxicity. Liposomal amphotericin B has proven to be as effective as conventional amphotericin B with less nephrotoxicity and infusion reaction. We report four cases of invasive fungal sinusitis who were treated with liposomal amphotericin B after having severe side effects from conventional amphotericin B. There were two cases of mucormycosis and two cases of aspergillosis. All patients had diabetes millitus. One patient had systemic lupus erythematosus and another was receiving immunosuppressive drugs after kidney transplantation. All cases needed multiple operations for sinus surgery. Two cases had acute reaction to amphotericin B infusion, one had active lupus nephritis with renal insufficiency, and one was considered treatment failure from amphotericin B. The patients received liposomal amphotericin B at the total doses of 4.55-8.85 g. Two cases of mucormycosis were considered to be successfully treated. In cases of aspergillosis, one was considered improved and another one with immunocompromised status died with active disease. From our experience, surgery is the main treatment for patients with invasive fungal sinusitis and liposomal amphotericin B is an effective alternative drug for adjuvant medical treatment. However, the degree of immunosuppression of the patients, the extension of fungal sinusitis and perhaps the species of fungus are important factors determining the clinical response.

Preliminary report for the application of nucleic acid sequence-based amplification in detection of human cytomegalovirus (HCMV) late pp67 mRNA for diagnosis of HCMV infection.

Human cytomegalovirus (HCMV) late pp67 mRNA expression by nucleic acid sequence-based amplification (NASBA) in patients, clinically diagnosed as possible HCMV, probable HCMV disease, and no disease, was evaluated. The RNAs were isolated from 11 whole-blood samples of 11 patients for the specific amplification of the pp67 mRNA. NASBA results were compared to results from PCR assay and serological assay. The HCMV pp67 mRNA could be found in 3 of 11 patients, whereas, HCMV-DNA PCR was positive in 6 of 11 patients. PCR assay for HCMV-DNA in plasma has proved to correlate with clinical diagnosis of HCMV infection. Only 2 patient samples of NASBA positive results coincided with HCMV-DNA PCR. However, the diagnosis of clinically relevant HCMV infection by NASBA was seen. Anti-CMV IgG titers of 1:1,600 or over 1:1,600 were found in 2 of 3 NASBA positive cases and 5 of 6 HCMV-DNA positive cases, whereas, anti-CMV IgM were all negative. These results showed the correlation of HCMV infection detected by NASBA, PCR assay and anti-CMV IgG of the titers up to 1:1,600. Additionally, a low antibody titer of the HIV patient could be diagnosed by NASBA or PCR. In conclusion, pp67 mRNA NASBA appears to be a promising diagnostic tool in analysis of HCMV infection and/or disease. Its diagnostic value should be defined in the specific group for the follow-up of immunocompromised patients, such as organ transplant recipients in future prospective studies.

Predictors of clinical progression in HIV-1-infected adults initiating combination antiretroviral therapy with advanced disease in the Asia-Pacific region: results from the TREAT Asia HIV observational database.

The majority of HIV-infected patients in developing countries commences combination antiretroviral therapy (cART) with advanced disease. We examined predictors of disease progression in patients initiating cART with CD4 count ≤200 cells/mm(3) in the TREAT Asia HIV Observational Database. The main outcome measure was progression to either an AIDS-defining illness or death occurring 6 months after initiation of cART. We used survival analysis methods. A total of 1255 patients contributed 2696 person years of follow-up; 73 were diagnosed with AIDS and 9 died. The rate of progression to the combined end point was 3.0 per 100 person years. The factors significantly associated with a higher risk of disease progression were Indian ethnicity, infection through intravenous drug use, lower CD4 count, and hemoglobin ≤130 g/dL at 6 months. In conclusion, measurements of CD4 count and hemoglobin at month 6 may be useful for early identification of disease progression in resource-limited settings.

HIV-1 drug resistance at virological failure versus immunological failure among patients failing first-line antiretroviral therapy in a resource-limited setting.

Antiretroviral treatment failure has been defined by immunological failure (IF) in some resource-limited settings whereas defining by virological failure (VF) has been widely used in developed countries. There is limited comparison of the levels of HIV-1 drug resistance between using VF and IF for the diagnosis of treatment failure. A retrospective cohort study was conducted among HIV-1-infected patients failing first-line antiretroviral therapy (ART). Of 95 patients, median CD4 and HIV-1 RNA were 158 cells/mm(3) and 10,200 copies/mL, respectively. Patients in the IF group had higher HIV-1 RNA than those in VF group (23,820 versus 9510 copies/mL, P = 0.008). Nucleoside reverse transcriptase inhibitor (NRTI)-, non-NRTI- and protease inhibitor-resistance-associated mutations (RAMs) were observed in 57.9%, 94.7% and 5.3%, respectively. Q151M, a multidrug RAM, was more commonly observed in the IF group (14.8% versus 2.9%, P = 0.032). Using IF to diagnose treatment failure is associated with higher HIV-1 RNA levels and a higher rate of Q151M, which can limit the options for second-line ART.

Isoniazid preventive therapy and 4-year incidence of pulmonary tuberculosis among HIV-infected Thai patients.

SETTING: Human immunodeficiency virus (HIV) clinics at two Thai tertiary care medical centres. OBJECTIVES: To evaluate the efficacy of tuberculin skin test (TST) guided isoniazid preventive therapy (IPT) in combination with antiretroviral therapy (ART) in the prevention of tuberculosis (TB). DESIGN: A 4-year prospective comparative study of patients at two HIV clinics: one performed TST at enrolment and, if positive, prescribed IPT (IPT group), while the other did not perform TST (non-IPT group). RESULTS: There were 200 patients included in each group. Baseline characteristics and drop-out rates were similar in both groups. The incidence of pulmonary TB over 4 years was not significantly different between the IPT and non-IPT groups (0.80 cases vs. 1.76 per 100 person-years [py], P = 0.13). However, the incidence of pulmonary TB in the non-IPT group was significantly higher during the first 6 months (8.60 vs. 0 cases/100 py, P = 0.01) and among patients with initial CD4 < 200 cells/l (9.41 vs. 0 cases/100 py, P = 0.02). The survival analyses demonstrated a protective effect of IPT (x(2) = 3.66, P = 0.04) for early TB. CONCLUSIONS: Benefit of IPT plus ART was evident only in the first 6 months of care. These findings suggest that TST-guided IPT should be routinely provided for HIV-infected patients after initial entry into medical care.

Tuberculin skin test and isoniazid prophylaxis among health care workers in high tuberculosis prevalence areas.

The tuberculin skin test (TST) is an important tool for the detection of latent tuberculosis (TB) and the identification of health care workers (HCWs) who require chemoprophylaxis. Although TST is inexpensive, easily available and the preferred test in most TB-prevalent settings, it has recognised limitations, including subjective interpretation, false positivity, cross reactivity with non-tuberculous mycobacteria, administration errors and the requirement for two visits. Given these limitations and the unavailability of better screening tests in resource-limited settings, the acceptance rate for chemoprophylaxis among HCWs has remained low. Furthermore, chemoprophylaxis in these settings is complicated by the high rate of drug-resistant TB, potential adverse reactions, prescription of chemoprophylaxis in undiagnosed active TB patients and the unavailability of follow-up systems provided by occupational health programmes. In the present article, we provide our viewpoint and a practical approach along with existing evidence supporting or discouraging the use of TST and isoniazid chemoprophylaxis for TB screening and management among HCWs in TB-prevalent settings.

Standard-dose efavirenz vs. standard-dose nevirapine in antiretroviral regimens among HIV-1 and tuberculosis co-infected patients who received rifampicin.

BACKGROUND: There is limited comparative data between efavirenz (EFV) 600 mg/day and nevirapine (NVP) 400 mg/day-based antiretroviral therapy (ART) among HIV-1 patients with tuberculosis (TB) and receiving rifampicin. METHODS: A retrospective cohort study was conducted in all ART-naïve patients who were receiving rifampicin between January 2002 and December 2005. RESULTS: Of 188 patients, 77 and 111 patients were initiated on EFV-based ART (EFV group) and NVP-based ART (NVP group), respectively. Overall, median [interquartile range (IQR)] CD4 count was 36 (15-77) cells/microL and median (IQR) viral load was 5.6 (5.2-5.9) HIV-1 RNA log copies/mL. At 48 weeks, 77.9% (60/77) in the EFV group and 67.6% (75/111) in the NVP group achieved HIV-1 RNA <50 copies/mL (P=0.140, odds ratio=0.590, 95% confidence interval=0.302-1.153). At 24 and 48 weeks, respective median CD4 counts were 174 and 254 cells/muL in the EFV group and 156 and 218 cells/microL in the NVP group (P>0.05). By binary logistic regression, treatment group was not associated with HIV-1 RNA <50 copies/mL (P>0.05). No patient in the EFV group and eight (7.2%) patients in the NVP group discontinued ART because of adverse reactions (P=0.084). CONCLUSIONS: For HIV-TB co-infected patients who receive rifampicin, efficacy of 600 mg EFV-based and 400 mg NVP-based ART may be similar, although adverse events tend to be higher in NVP-based ART.

Malignancies in HIV-infected Thai patients.

Of 1416 HIV-infected patients seen at Ramathibodi Hospital over a 5-year period (1999-2003), 42 were diagnosed with malignancies, giving a prevalence of 3%. Twenty-one of these patients (50%) were men and their mean age was 40.8 years. The median CD4 cell count was 235 cells/muL. AIDS-related malignancies were found in 26 patients (62%). The most common AIDS-related malignancies were non-Hodgkin's lymphoma (NHL) (33%), cervical cancer (21%) and Kaposi's sarcoma (KS) (5%). Breast cancer was the most common non-AIDS-related malignancy (10%). Eleven patients (26%) died. The 75% survival time of patients who received treatment for their malignancy was longer than that of patients who received no treatment (18.3 vs 1.2 months; P<0.01).

Predictors of immunity after hepatitis A vaccination in HIV-infected persons.

Hepatitis A virus (HAV) infection remains a health risk for human immunodeficiency virus (HIV)-infected persons. While the inactivated HAV vaccine affords protection to immunocompetent persons >95% of the time, rates of developing protective antibody (anti-HAV) in HIV+ persons are considerably lower. Although low CD4+ T-cell counts have previously been reported to be correlated with this poor response, the effect of HIV viraemia on HAV vaccine response has not previously been reported. The medical records of HIV-infected patients who had received at least one dose of HAV vaccine (Havrix, 1440 EIU) were reviewed for factors associated with the development of a protective anti-HAV response. Serological data with regard to anti-HAV status after vaccination were available in 238 patients with 133 individuals (49.6%) developing immunity after vaccination. In a logistic regression model, the only factors associated with a protective antibody response were an HIV plasma RNA level <1000 copies/mL at the time of vaccination (P = 0.011) and male gender (P = 0.016). Neither nadir CD4+ T cell count nor CD4+ T-cell count at time of vaccination were predictive of the development of anti-HAV. Suppression of HIV replication at time of vaccination is associated with a protective antibody response to HAV vaccination in HIV-infected adults. The low rate of response warrants further research in alternative strategies for HAV vaccination among HIV-infected persons.