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.

Compliance with hepatitis B and hepatitis C virus infection screening among HIV-1 infected patients in a resource-limited setting.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important risk factors for mortality among HIV-infected patients. We assessed compliance with screening for HBV and HCV infection prior to initiation of ART in a resource-limited setting. Six hundred thirty-eight patients with a mean age of 38.4 years (53% males) were studied. Prior to initiation of antiretroviral therapy (ART) 371 patients (58%) were screened for HBV and 273 (43%) were screened for HCV infection. Of those screened, 9.7% had HBV infection and 8.8% had HCV infection. Given the relatively high prevalence of HBV and HCV infection among HIV-infected patients, screening for HBV and HCV infections prior to ART initiation should not be omitted in the resource-limited setting.

Incidence and risk factors of nevirapine-associated severe hepatitis among HIV-infected patients with CD4 cell counts less than 250 cells/microL.

OBJECTIVES: To determine incidence and risk factors of nevirapine (NVP)-associated severe hepatitis that led to NVP discontinuation among HIV-infected patients with CD4 < 250 cells/microL. MATERIAL AND METHOD: A retrospective cohort study was conducted among antiretroviral-naïve HIV-infected patients who had baseline CD4 < 250 cells/microL and were initiated NVP-based antiretroviral therapy (ART) between January 2003 and October 2005. All patients were categorized to group A: occurred clinical hepatitis and group B: did not occur clinical hepatitis. All were followed until 6 months after ART. RESULTS: There were 910 patients with a mean age of 35.4 years, 57% were males and median (IQR) CD4 cell count was 27 (9-80) cells/microL; contributing 5,006 person-months of observations. Ten (1.1%) patients were in group A and 900 (98.9%) patients were in group B. Incidence of clinical hepatitis was 2 per 1,000 person-months. Probabilities of clinical hepatitis at 0.5, 1, 2, 3 and 6 months after ART were 0.2%, 0.5%, 0.7%, 0.8% and 1.1%, respectively. By Cox regression analysis, baseline AST > or = 1.5 times of upper limit was associated with higher incidence of clinical hepatitis (p = 0.019, HR = 5.83, 95% CI = 1.33-25.51). CONCLUSION: Incidence of NVP-associated severe hepatitis that lead to NVP discontinuation among HIV-infected patients with baseline CD4 < 250 cells/microL is low. The higher baseline AST is also associated with a higher risk of severe hepatitis.

Survival time of HIV-infected patients with cryptococcal meningitis.

OBJECTIVE: To study survival time and risk factors of mortality among HIV-infected patients who had cryptococcal meningitis. DESIGN: Retrospective cohort study. MATERIAL AND METHOD: Patients' medical records of those who had HIV-infection with newly diagnosed cryptoccocal meningitis between January 2002 and December 2004 were reviewed. Each patient was classified into one of two groups, according to their anti-retroviral status (ART). RESULTS: Five hundred and forty nine patients enrolled in the present study: 281 (51.2%) in the ART+ group and 268 (48.8%) in the ART-group. The mean age was 33.4 +/- 6.9 years old in the ART + group and 33.6 +/- 7.0 years old in the ART-group. There were more male in both groups: 207 males and 74 females in the ART+ group, and 195 males and 73 females in the ART-group. Baseline CD4 cell count of both groups was 20 (6-74) cells/mL and 24 (9-72) cells/ml. About 30% of both groups of patients experienced major opportunistic infection before cryptococcal meningitis. All patients were treated by standard amphotericin B for a 2-week duration followed by fluconazole for an additional 8 weeks. There were no differences of baseline characteristics between the two groups (p > 0.05). The survival rates at 12, 24, and 36 months were 92.8%, 87.4%, and 85.4% in the ART+ group and 55.3%, 42.2%, and 36.8% in the ART- group, respectively (p < 0.01). The median survival time in the ART- group was 15 months. From the Cox regression model, the hazard ratio for "not received ART" was 4.87 (95%CI = 2.48-9.44, p < 0.01). CONCLUSION: The present study demonstrated the substantial increasing of survival time of HIV-infected patients with cryptococcal meningitis by initiated ART even in a resource limited setting (no flucytosine, local combined antiretroviral drugs with NVP based regimens).

Declining prevalence of drug-resistant tuberculosis among HIV/tuberculosis co-infected patients receiving antiretroviral therapy.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a serious threat in developing countries where the prevalence of both HIV and TB are high. Antiretroviral therapy (ART) has been more accessible in these countries. The present study aimed to determine the impact of ART on the prevalence of DR-TB among HIV/TB co-infected patients. MATERIAL AND METHOD: A retrospective cohort study was conducted among HIV-infected patients with culture-proved TB from 1999 to 2004. Susceptibilities of Mycobacterium tuberculosis to antituberculous drugs and rate ofART use were studied. RESULTS: There were 225 patients, mean age 35.8 years, 72.4% male and median CD, 44 cells/mm(3). Patients who had received ART increased from 18.5% in 1999 to 92.1% in 2004 (p<O. 001). The prevalence of DR-TB in the years 1999 and 2004 were 48% and 7.9%, respectively (p<O.001). The prevalence of isoniazid- and rifampicin-resistance significantly declined in 2004 when compared with those in 1999 (p<O. 05). CONCLUSION: The declines in the prevalence of DR-TB, INH- and RFP-resistance in HIV/TB co-infected patients are possibly attributable to the use of ART In addition to the survival benefit from ART in HIV-infected patients, increasing use of ART among HIV-infected patients may eliminate DR-TB in this population.

Plasma nevirapine levels and 24-week efficacy of a fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-VIR) among Thai HIV-infected patients.

BACKGROUND: A fixed-dose combination of stavudine, lamivudine, and nevirapine (GPO-VIR) is the most affordable antiretroviral therapy (ART) regimen in Thailand. The data of nevirapine (NVP) level and efficacy of this fixed-dose combination is limited. MATERIAL AND METHOD: Patients who were initiated GPO-VIR in 2004 were enrolled NVP levels at 12 weeks were determined. Patients were followed for 24 weeks. RESULTS: Fifty-nine patients with a mean age of 36.4 years and 54% male were enrolled. Mean body weight was 54.7 kgs. Median baseline CD4 and HIV-RNA were 29 cells/mm3 and 270,000 (5.4 log10) copies/mL, respectively. Mean plasma NVP levels at 12 weeks was 6.4 mg/L. By linear regression, female gender (p = 0.042), and higher weight (p = 0.020) were associated with lower NVP levels. At 24 weeks, 78% achieved undetectable HIV-RNA and median CD4 was 156 cells/mm3. CONCLUSION: NVP levels and 24-week efficacy of GPO-VIR are favorable. According to the affordable cost, GPO-VIR should be an appropriate initial regimen for naïve HIV-infected patients in resource-limited settings.

Virological and immunological responses of efavirenz-based HAART regimen initiated in HIV-infected patients at CD4 < 100 versus CD4 > or = 100 cells/mm3.

OBJECTIVE: To compare virological and immunological responsiveness of efavirenz (EFV)-based highly active anti retroviral therapy (HAART) between patients with baseline CD4 < 100 and CD4 > or = 100 cells/mm3. MATERIAL AND METHOD: A prospective cohort study in antiretroviral-naive HIV-infected patients was conducted between February and April 2002. Donated HAART regimen, consisting of stavudine, didanosine, and EFV was initiated. The primary outcome was time to undetectable HIV RNA, < 50 copies/mL. Patients were followed up every 12 weeks until 48 weeks (the end of the study). RESULTS: Forty-six patients were included, 21 patients for CD4 < 100 cells/mm3 and 25 patients for CD4 > or = 100 cells/mm3. Median CD4 cell counts of these corresponding groups were 26.5 and 177 cells/mm3. Patients' characteristics were similar between the two groups except CD4. The probability of undetectable HIV RNA at 12, 24, 36, and 48 weeks were 57.1% (95% CI, 37.7-78.1%), 76.2% (95% CI, 56.9-91.3%), 80.9% (95% CI, 62.3-94.0%), and 90.5% (95% CI, 68.9-99.1%) for the former group; and 64.0% (95% CI, 45.8-81.8%), 92.0% (95% CI, 77.5-98.6%), 96.0% (95% CI, 83.0-99.7%), and 96.0%.(95% CI, 83.0-99.7%) for the latter group. Median time to undetectable HIV RNA was 12 weeks for both groups. Median CD4 change at 48 weeks was 171 and 132 cells/mm3, respectively (p = 0.232). The adverse events were similar between the two groups. CONCLUSION: Initiation of EFV-based HAART regimen in HIV-infected patients at CD4 < 100 and > or = 100 cells/ mm3 gains similar immunological and virological response.

Antifungal susceptibilities of Cryptococcus neoformans cerebrospinal fluid isolates and clinical outcomes of cryptococcal meningitis in HIV-infected patients with/without fluconazole prophylaxis.

OBJECTIVES: To compare the MICs of FLUconazole (FLU) and amphotericin B against isolates of Cryptococcus neoformans (C. neoformans) obtained from the CerebroSpinal Fluid (CSF); and clinical outcomes of HIV-infected patients diagnosed with cryptococcal meningitis. MATERIAL AND METHOD: There were two groups including those who did not receive FLU (group A) and those who did receive either FLU 400 mg/week for primary prophylaxis cryptococosis or 200 mg/day for secondary prophylaxis cryptococosis (group B). CSF isolates of C. neoformans from group A and group B between January 2003 and October 2004 were retrospectively studied. The MICs were determined by using the standard NCCLS broth microdilution methods (M27-A). The MICs of FLU and amphotericin B, and clinical outcomes after 10 weeks of cryptococcal meningitis treatment were determined. RESULTS: There were 98 isolates; 80 in group A and 18 in group B. The patients in group B had a higher proportion of previous opportunistic infections (p = 0.008). The other baseline characteristics between the two groups were not different. The median (range) MIC of FLU was 8.0 (0.5-32) microg/ml in group A, and 6.0 (0.5-32) microg/ml in group B (p = 0.926). The median (range) MIC of amphotericin B was 0.25 (0.03-1.0) microg/ml in group A, and 0.25 (0.12-1.0) microg/ml in group B (p = 0.384). Sixty patients from group A and 14 from group B received standard treatment and continued to follow-up. After the 10-week treatment, 39/60 (65%) patients in group A and 7/14 (50%) in group B had complete recovery (p = 0.364; RR = 0.538, 95%CI = 0.166-1.742). The overall mortality rate was 14/60 (23.3%) in group A and 7/14 (50.0%) in group B (p = 0.096; RR = 3.286, 95%CI = 0.983-10.979). CONCLUSION: The MICs of FLU and amphotericin B against CSF isolates of C. neoformans and clinical outcomes between HIV-infected patients who receive or did not receive FLU prophylaxis are not different.

Prevalence of hepatitis B virus and hepatitis C virus co-infection with human immunodeficiency virus in Thai patients: a tertiary-care-based study.

BACKGROUND: Hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV share the route of transmission. HBV or HCV co-infection with HIV has been associated with a reduced survival rate, an increased risk of progression to severe liver disease, and an increased risk of hepatotoxicity associated with active antiretroviral therapy. Information regarding prevalence of HBV and HCV co-infection with HIV in Thailand is limited. PATIENTS AND METHOD: A cross-sectional study of prevalence and risk factors of HBV and HCV co-infection in HIV-infected patients was conducted. All HIV-infected patients who were cared for in March 2003 at Ramathibodi Hospital were included. RESULTS: There were 529 HIV-infected patients with a mean age of 36.7 years and 56.5% males. Of these, 58.8% lived in Bangkok, whereas, the others were from provincial areas. Heterosexual contact were the acquisition of HIV infection in 98.1% of all patients. The prevalence of HBV infection was 8.7%, and HCV infection was 7.8%. There was no difference between the prevalence of these infections in Bangkok and provincial areas (p = 0.115). History of intravenous drug use was associated with both HBV and HCV co-infection (p < 0.001). HCV co-infection group was also associated with male gender (p = 0.002) and elevated serum alanine transaminase (ALT) level (p = 0.0003). CONCLUSIONS: The prevalence of HBV and HCV co-infection with HIV in Thai patients is significant. In the author s resources-limited setting, history of intravenous drug use is a major indicator to screen for both HBV and HCV co-infection. Male gender and elevated serum ALT level are also suggestive of HCV co-infection.

Concurrent chromomycosis and aspergillosis of the maxillary sinus.

The authors describe a rare case of an infection of both the chromomycosis and aspergillosis of the maxillary sinus in an immunocompetent 72-year-old female who presented with progressive visual loss and dull aching pain of the left eye. Sinuscopy of the left maxillary sinus showed swelling of the mucosa with clay-like materials. Biopsy from the left maxillary sinus showed the typically characteristic morphology of chromomycosis and culture from sinus tissue which yielded Aspergillus. The patient responded to a combination therapy of surgical excision and antifungal agent.

Case report: Brucellosis: a re-emerging disease in Thailand.

Brucellosis is a zoonotic disease prevalent in many countries, but it has been reported only once in Thailand, 36 years ago. We describe here two consecutive cases of brucellosis in Bangkok, Thailand. Both cases presented with prolonged fever and weight loss. Blood cultures taken from 2 patients yielded Brucella melitensis. The slide agglutination test of blood samples were also positive, with a titer of 1:64 for antibodies to Brucella. The first patient responded to a combination of doxycycline, gentamicin, and ciprofloxacin; the other responded to doxycycline and rifampicin. Brucellosis is a potential public health threat, therefore, preventive measures should be actively implemented. This clinical syndrome should be included in the differential diagnosis of patients presenting with prolonged fever, particularly those with contact to animals which could serve as reservoirs.