Factors Affecting Discordance between Sputum Smear and Culture Conversion Rates In Newly Diagnosed Pulmonary Tuberculosis: A Retrospective Study in Developing Country.

Aims: To assess the performance of sputum AFB smear for monitoring treatment response and outcome of anti-tuberculous drugs among newly diagnosed smear positive pulmonary TB patients. Study Design: This study was conducted prospectively among newly diagnosed smear positive pulmonary TB patients. Place and Duration of Study: Queen Savang Vadhana Memorial Hospital and Chonburi Regional Hospital, Chonburi province, Thailand during April 2010 and July 2012. Methodology: Sputum AFB smear, culture and drug susceptibility test were performed at the time of diagnosis, the second and the fifth month of treatment. Baseline characteristic, clinical and laboratory parameters, treatment regimens and adverse events were recorded. Descriptive statistics and multiple logistic regression analysis were applied as appropriate. The performance of sputum AFB smear for monitoring treatment response and outcome of anti-tuberculous drugs was done using culture as the gold standard. Results: Of 297 eligible pulmonary TB cases, majorities were male (72.4%) with median age of 39 years, illiterate to low educated (52.6%) and earning low income (77.5%). Cough was the most common symptom (91.2%) and cavity was present in 31.1%. At the second month, 17.0% of patients had discordance between sputum AFB smear and culture. High bacilli load (adjusted OR=2.38, CI=1.09-5.18), and hearing alteration (adjusted OR=10.98, CI=1.79-67.28) were significant predictors. Hypoalbuminemia was significantly more severe in patients with false positive AFB smear (P=.04). Sensitivity and specificity for AFB smear were 44.7% and 89.6% at the second month and 57.1% and 97.5% at the fifth month, respectively. MDR-TB was diagnosed in 1.0% and success rate was 77.1%. Conclusions: Baseline AFB smear ≥ 2+ and hypoalbuminemia as well as adverse events during intensive phase are strongly recommended as the criteria to prioritize culture and DST for new smear positive pulmonary TB patients with positive AFB smear at the second and the third month of treatment in developing countries.

Expanding research capacity and accelerating AIDS vaccine development in Asia.

According to the Joint UN Program on AIDS (UNAIDS), an estimated 4.9 million adults and children are living with HIV in Asia and the Pacific. Refinement and development of existing and new prevention and treatment technologies--including safe, effective, and accessible AIDS vaccines--are urgent public health priorities. The Asian region faces several challenges for AIDS vaccine development. There are multiple genetic variants of HIV-1 driving the epidemic in the region and too few vaccine candidates in the pipeline targeting those subtypes. Low HIV incidence throughout the region means that trial sites must recruit larger numbers of volunteers and shift their focus to higher-risk populations where incidence is higher. Also, the cultural, economic, and political diversity of the region may render collaboration very complex, but also beneficial at a regional level. Recognizing that collaborating as a region could foster and accelerate AIDS vaccine development, participants at the Sapporo International Consultation recommended that an AIDS Vaccine Asian Network (AVAN) be created to facilitate interactions between donors and funding opportunities, increase regional clinical trial and production capacity, support region-specific advocacy and communication strategies, contribute to the Global HIV Vaccine Enterprise Scientific Plan, prepare a regional approach for future vaccine deployment, and develop a regional platform for clinical trials including harmonized legal, regulatory, and ethical frameworks.

Predisposing factors for nevirapine toxicity among AIDS patients with low baseline CD4 count.

The objective of the study was to determine the predisposing factors and incidence of toxicity among AIDS patients treated with a nevirapine (NVP)-based regimen in clinical practice. A retrospective cohort study of representative samples of AIDS patients treated with a NVP-based regimen was performed. A total of 206 adult HIV/AIDS cases with median age (IQR) 33 years (range, 29-38 years), 51% male, treated between January 2004-December 2005, were included. Most (92.2%) of the patients were naïve to antiretroviral drug. The incidence of NVP toxicity was 1.09/100 person-months. The median onset time was 4 weeks post NVP initiation (2.57 weeks for skin toxicity and 12.43 weeks for hepatic toxicity). History of drug allergy and NVP toxicity were significantly associated (p = 0.006), as were sulfamethoxazole allergy and toxicity (p = 0.015). Regarding concomitant medication, concurrent anti-tuberculosis drugs significantly increased the risk of NVP associated liver toxicity (p = 0.001). Therefore, it is important to monitor adverse events from NVP, including liver function tests among HIV/AIDS patients with history of drug allergy, especially against sulfamethoxazole, and those concurrently treated with antituberculosis drugs.

Social harms in injecting drug users participating in the first phase III HIV vaccine trial in Thailand.

OBJECTIVE: To study related social harms due to identification with a group of participants in an HIV-1 vaccine trial who are potentially high risk for HIV/AIDS. MATERIAL AND METHOD: Two thousand five hundred forty six injecting drug users (IDU) were enrolled in a 36-month vaccine trial. Volunteers received education and risk reduction counseling at every six-month study visit. Social harms were not actively solicited, but volunteers were encouraged to report any during the process of counseling at every six-month visit. If a social harm was reported, a questionnaire was administered and the harm was tracked If necessary, clinic staff assisted in resolving the social harm. RESULTS: Thirty-nine social harms were reported by 37 participants; 33 (84.6%) were disturbances in personal relationships, three (7.7%) in employment, one (2.6%) was medically related, one (2.6%) was related to admission in the military and one (2.6%) was related with misbelieve about the vaccine. The most common reason for disturbances in personal relationships was suspicion of HIV infection (n=20). The impact of these harms on quality of life was characterized as minimal by 31 (79.5%) participants, as moderate by seven (17.9%), and as major by one (2.6%). All social harms were documented to be resolved by the end of the study. CONCLUSION: A few participants reported study-related social harms during the course of the trial. Most harm had minimal impact and all could be resolved by the end of the present study.

Outcomes in HIV-infected patients on antiretroviral therapy with tuberculosis.

HIV-infected patients with active tuberculosis (TB) having CD4 counts < 100/mm3 and who were antiretroviral therapy (ART) naïve were reviewed retrospectively to determine the outcomes of their tuberculosis infection. All patients received ART at or after receiving anti-TB treatment. Clinical manifestations, treatment regimens and outcomes were analyzed. Of 101 patients, 62 (61.4%) completed TB treatment. Of these, 53.2% were treated with a 6-month standard TB regimen, while the rest were treated with prolonged TB regimens. The median interval between anti-TB treatment and ART was 68 days (range: 0-381). Among the clinically cured patients 66.1% received rifampin concomitantly with nevirapine, and 32.3% received rifampin concomitantly with efavirenz. The treatment success rate was 75.6%, with a mortality rate of 6.1%. The risk factors for death were resistant TB (p = 0.03) and poor compliance (p < 0.05). Seven point nine percent had multi-drug resistant TB. Possible or probable immune reconstitution inflammatory syndrome (IRIS) was seen in 15 cases (14.9%). No life-threatening IRIS was reported, and it did not affect disease outcome (p = 0.5). A shorter time between anti-TB treatment and ART onset was associated with the occurrence of IRIS (31 days vs 90 days; p < 0.05). Regarding adverse drug effects, 44.6% had side effects due either to anti-TB drugs or ART. Sixty-six point one percent of them occurred within the first 2 months of TB treatment, and 43 (76.8%) had to stop or change either anti-TB treatment or ART. The mortality rate with TB and HIV on ART was low and the occurrence of IRIS did not carry any additional mortality.

Comparison of one week with two week regimens of amphotericin B both followed by fluconazole in the treatment of cryptococcal meningitis among AIDS patients.

BACKGROUND: Amphotericin B treatment in cryptococcosis requires daily hospital visits or admission. Its toxicities and hospital costs have been concerned. Short course amphotericin B regimen warrants to be evaluated. OBJECTIVE: To compare the safety and efficacy of one-week (AmB1) with two-week (AmB2) amphotericin B both followed by fluconazole. MATERIAL AND METHOD: 57 AIDS with cryptococcal meningitis were randomly assigned to either AmB1 or AmB2. Microbiological and clinical clearances were the outcomes of the study. RESULTS: The treatment success at 6 weeks was 63.3% in AmB1 and 70.4% in AmB2 (p = 0.574). Clinical assessment at week 10 and renal toxicities were not significantly different between both regimens. Mortality rate was 14% however, 75% of deaths were in AmB2. CONCLUSION: AmB1 was comparably effective and safe as the standard AmB2 regimen in the treatment of AIDS related cryptococcal meningitis. It can be an alternative regimen to lower hospital based care and improve cost effective for source limiting health care centers.

Efficacy and safety of generic fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-vir) in advanced HIV infection.

OBJECTIVES: To assess the efficacy and safety of generic fixed-dose combination of stavudine, lamivudine and nevirapine; GPO-vir in advanced HIV infection. MATERIAL AND METHOD: Open-label combined prospective and retrospective study involving 102 HIV infected patients with baseline CD4 cell count < 100 cells/mm3. All patients received GPO-vir for 48 weeks. The CD4 cell count and plasma viral load (pVL) was measured at 48 weeks. RESULTS: The median baseline CD4 cell count and pVL were 13 cells/mm3 and 363,500 copies/ml, respectively. At 48 weeks, the median CD4 cell count increased to 191 cells/mm3 and 63.7% in intention-to treat and 82.3% in on-treatment analysis had pVL < 50 copies/ml. There was no significant difference in pVL between patients with baseline pVL > 100,000 or < or = 100,000 copies/ml (p = 0.312). The incidence of hepatotoxicity, rash and peripheral neuropathy was 4.9%, 14.7% and 6.9%, respectively. CONCLUSION: GPO-vir was well tolerated and effective in increasing CD4 cell count and suppressing plasma viremia in advanced HIV infection during the 48 weeks follow-up period.

Clinical features, etiology and short term outcomes of interstitial pneumonitis in HIV/AIDS patients.

A prospective study was conducted at Bamrasnaradura Hospital, Nonthaburi Province, Thailand from November 11, 2002 to January 5, 2003. A total of 59 HIV/AIDS patients with interstitial infiltrates on chest radiographs were included in the study. The objectives of this study were to describe the clinical manifestations and determine the etiologies of interstitial pneumonitis, assess the short-term outcomes and determine the accuracy of the clinical diagnosis of the etiologies of interstitial pneumonitis in HIV/AIDS patients at Bamrasnaradura Hospital, Nonthaburi, Thailand. Tuberculosis was the most common diagnosis (44%), followed by Pneumocystis carinii pneumonia (25.4%), bacterial pneumonia (20.3%) and fungal pneumonia (10.2%). In tuberculosis, compared to other diagnoses, a mild cough (p = 0.031), pallor (p = 0.021), lymphadenopathy (p < 0.001), absence of skin lesions (p = 0.003), higher mean body temperature (p = 0.004) and an absence of dyspnoea on exertion (p = 0.042) were significant findings. On multivariate analysis, however, only an absence of skin lesions (p = 0.023) remained a statistically significant predictor of TB. In Pneumocystis carinii pneumonia compared to other diagnoses, dyspnea on exertion (p = 0.014), non-purulent sputum production (p = 0.047), a higher mean respiratory rate (p < 0.001), absence of lymphadenopathy (p < 0.001) and lack of purulent sputum (p = 0.030) were significant factors. By multivariate analysis, only an absence of lymphadenopathy were shown to be independently and statistically significantly associated (p = 0.040). In bacterial pneumonia, compared to other diagnoses, production of purulent sputum (p = 0.014), hemoptysis (p = 0.006), pallor (p = 0), skin lesions (p = 0.002) and a severe cough (p = 0.020) were significantly associated factors. On multivariate analysis, none of these factors were statistically significant. In fungal pneumonia, compared to other diagnoses, headache and papulonecrotic skin lesions were common findings, but no factor had a significant association. After four weeks, 59.3% of the patients were alive, 13.6% died and 27.1% were lost to follow-up. Among the alive patients 88.6% had clinically improved. On multivariate analysis, no factor was shown to be a statistically significant predictor of death. The cumulative survival after 28 days was highest among PCP patients, followed by bacterial pneumonia, tuberculosis and fungal pneumonia, but this difference was not statistically significant (p = 0.0453).

The efficacy and adverse effects of GPO-VIR (stavudine+lamivudine+nevirapine) in treatment-naïve adult HIV patients.

A descriptive, combined retrospective and prospective study was conducted at the Anonymous Clinic, Chon Buri Hospital, Chon Buri Province, Thailand from November 10, 2003 to January 4, 2004. A total of 83 adult HIV-treatment-naïve patients undergoing treatment with GPO-VIR (stavudine, lamivudine, and nevirapine) for at least one year were studied. The objectives of the study were to assess the efficacy of GPO-VIR by evaluating body weight changes, CD4 T-cell count changes, the occurrence of opportunistic infections, and long-term side effects, such as lipodystrophy, during treatment. Of 83 studied patients, approximately half (52.3%) of them had a body weight increase > 10% of pre-treatment body weight after 12 months treatment. After taking GPO-VIR, CD4 T-cell counts increased rapidly, by a median of 78 x 10(6) cells/l during the first three months. 39.5% of the patients attained median CD4 counts > 200 x 10(6) cells/I, and 11.6% achieved > 500 x 10(6) cells/l after 2 years of treatment. The occurrence of opportunistic infections was significantly lower after treatment with GPO-VIR (p = 0.001). Subjective assessment of lipodystrophy by physicians and patients showed that 16.8% had symptoms of lipodystrophy within 2 years of GPO-VIR treatment. There was a significant association between older age group (40-49 years) and occurrence of lipodystrophy (p = 0.043). GPO-VIR is an inexpensive and effective antiretroviral drug regimen for initiating treatment of naïve patients, but careful assessment for lipodystrophy is necessary, especially after one year of treatment.

6-month evaluation of JinHuang Chinese herbal medicine study in asymptomatic HIV infected Thais.

Good results of in vitro study of anti-HIV effects of JinHuang, a Chinese herbal medicine led to in vivo study of safety and efficacy among asymptomatic HIV infected individuals. It was a prospective open study of 21 asymptomatic HIV infected Thai volunteers. Twelve and 9 were female and male, respectively, with mean age of 29.24 +/- 3.94 years. JinHuang preparation, 6 capsules and 2 bottles of liquid formula orally three times a day, was given on an outpatient basis initially for 6 months. Regular close monitoring and follow-up were done. The side effects reported included : increased bowel movements (81%), vague taste, and smell of drug after initiation (52%). No serious adverse event related to JinHuang was detected during study. No significant changes in terms of log viral load and CD4 count were observed after 6-months' duration. Most of the patients felt that the quality of life was better in terms of better appetite, good sleep and healthy during study participation, however, these were subjective.

Evaluation of attitude, risk behavior and expectations among Thai participants in Phase I/II HIV/AIDS vaccine trials.

The Understanding of volunteers in vaccine trials about their role as study participants and their voluntary commitment during the study are always one of the important concerns apart from evaluation of safety and efficacy of vaccine trials, especially in HIV prophylactic vaccine trials. The apprehension of indirectly risky behavior encouragement and deviated expectations among volunteers should be of concern. The current prospective cohort study aimed to assess and monitor the changes of risk behaviors, attitude and expectations among 164 volunteers from 2 studies of different prophylactic HIV vaccines, the Chiron HIV Thai E gp 120/MF59 +/- the Chiron HIV SF52 gp120 and Aventis Pasteur Live Recombinant ALVAC HIV (vCP1521) priming with VaxGen gp120B/E (AIDSVAX B/E) boosting. 113 males and 51 females with a mean age (+/- SD) of 28.82 +/- 7.97 years old were enrolled from October 1997 to December 1998 and February 2000 to April 2001. Education and risk reduction counseling were regularly performed at every visit and questionnaires about risk behaviors, knowledge, attitudes, social influences and expectations were asked at baseline, 4 months and 12 months. No change of potentially HIV transmission related risk behavior was observed during the studies. There was a statistically significant decrease of risk sexual practices from the beginning of the trials (42.2% vs 1%, p < 0.0001). While 35.2 per cent from 62.2 per cent of the volunteers at the beginning of the study continued sexual practice with an identified single sexual partner at the end of the study (p < 0.0001). All of the volunteers expressed the beneficial expectations as knowledge gain, social contribution, feelings of having gained merit and self-benefits from health check-ups.

Clinical and mycological responses to fluconazole and fluconazole MIC in oropharyngeal candidiasis in HIV-infected patients.

INTRODUCTION: OPC is a common opportunistic infection in HIV-infected patients. Although some patients are asymptomatic, progression of the disease may occur leading to esophageal candidiasis. Fluconazole resistant candidiasis has been reported in several international studies. OBJECTIVES: This study aimed to test the MICs (minimal inhibitory concentrations) to fluconazole of Candida species isolated from mouthwash specimens of 54 HIV positive patients with oral candidiasis. Clinical and mycological responses to fluconazole were also assessed in 16 patients. MATERIAL AND METHOD: This was a prospective study. Mouthwash specimens were cultured on sabouraud dextrose agar twice. Candida species identification was performed and MICs for fluconazole were obtained using NCCLS guidelines. Clinical and mycological responses were assessed on day 14 and 42 in 16 patients who received a 14-day course of fluconazole. RESULTS: 48/54 patients (88.89%) were found to carry pure C. albicans. The other 6 patients (11.11%) had mixed Candida species on cultures. Among these 6 patients, 5 patients had mixed C. albicans and C. glabrata, and 1 patient had C. albicans and C. krusei. Fluconazole MICs of C. albicans, C. glabrata, and C. krusei ranged from 0.125-32 (median=0.250), 4-64 (median=2), and 8 g/L respectively. This study showed that the MICs to fluconazole of oropharyngeal Candida was a good predictor of the therapeutic responses.

Mycobacterium tuberculosis infection among HIV/AIDS patients in Thailand: clinical manifestations and outcomes.

A one year retrospective study, was conducted at Bamrasnaradura Hospital, Nonthaburi Province, Bangkok, Thailand, of 271 subjects with both TB and HIV/AIDS. Single males (median age group 31 to 40 years) were most likely to develop co-infection. The commonest clinical manifestations on initial presentation included a low grade fever, cough, weight loss, lymphadenopathy with pancytopenia, and lung infiltrates. Multi-drug resistant TB (MDR-TB) was found in 26.6% of the subjects which was significantly associated with a past history of anti-TB treatment (p = 0.005; OR=2.5); it was also significantly associated with disseminated TB (p = 0.022; OR=1.9) and mortality (p= 0.013; OR=2.8). Analysis of clinical outcomes showed that 46.7% were lost to follow-up and 13.3% had died by the time of follow-up. Among those who survived, only 11.4% had been successfully treated; the rest had not improved due to relapse (2.9%), therapeutic failure (8.8%), treatment in progress (5.9%), and failure to complete treatment (10.7%).