Significant intolerability of efavirenz in HIV occupational postexposure prophylaxis.

BACKGROUND: Completion of human immunodeficiency virus (HIV) occupational postexposure prophylaxis (PEP) is important for successful prophylaxis. AIM: To determine factors associated with failure to complete the four-week HIV PEP. METHODS: A retrospective study was conducted among healthcare workers (HCWs) accidentally exposed to blood or body fluids of patients at the Bamrasnaradura Infectious Diseases Institute, Thailand, between March 1996 and June 2014. Logistic regression analysis was used to determine factors associated with failure to complete the four-week HIV PEP. FINDINGS: In total, 225 exposure episodes were reported. The mean age of HCWs was 33.1 (standard deviation 9.9) years, and 189 (84%) were female. Nurses (43%) were exposed most frequently. The HIV status of the source was defined in 149 (66%) episodes, and 101 (68%) of these were positive. Of 225 exposures, PEP was prescribed in 155 (69%) cases, with intentional discontinuation in 26 cases. Ninety-one of 129 (71%) HCWs completed the four-week regimen. Multi-variate analysis showed that a regimen of two nucleotide reverse transcriptase inhibitors (NRTI) + efavirenz (EFV) was the only significant factor associated with non-completion of the four-week course (odds ratio 37.8, 95% confidence interval 4.2-342.3; P < 0.01). Other factors including age, sex, staff position, status of the source and other PEP regimens were not associated with non-completion of the four-week course (P > 0.05). None of the HCWs were documented to have HIV seroconversion. CONCLUSION: A regimen of two NRTIs + EFV was significantly associated with premature discontinuation of occupational PEP. This regimen should not be used for HIV prophylaxis following occupational exposure.

Efficacy and tolerability of a double boosted protease inhibitor (lopinavir + saquinavir/ritonavir) regimen in HIV-infected patients who failed treatment with nonnucleoside reverse transcriptase inhibitors.

OBJECTIVES: Long-term nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral treatment failure in most developing countries has led to broad cross-resistance within NNRTI and nucleoside reverse transcriptase inhibitor (NRTI) classes. In this study, we investigated the efficacy and tolerability of a double boosted protease inhibitor (PI) regimen in this setting. METHODS: A total of 64 HIV-infected patients who had failed NNRTI-based regimens were randomized to receive either lopinavir/saquinavir/ritonavir [LPV/SQV/r; 400/1000/100 mg twice a day (bid)] alone or indinavir/ritonavir (IDV/r; 800/100 mg bid) plus two NRTIs optimized with genotypic drug resistance guidance. Patients who had no available optimized NRTI backbone were allocated to the LPV/SQV/r arm. RESULTS: At 48 weeks, the percentages of patients with plasma viral load<50 HIV-1 RNA copies/mL were 60% (31 of 52 patients) in the LPV/SQV/r arm vs 50% (six of 12) in the IDV/r/2NRTIs arm in the intent-to-treat (ITT) analysis, and 61% (31 of 51) vs 71% (five of seven), respectively, in the as-treated analysis. The median (interquartile range) increases in absolute CD4 cell count from baseline were 177 (91-269) and 100 (52-225) cells/microL in the LPV/SQV/r and IDV/r/2NRTIs groups, respectively (P=0.32). Four of 12 patients (33%) in the IDV/r/2NRTIs group experienced severe nausea and vomiting and four patients (8%) in the LPV/SQV/r group had significant hepatitis. CONCLUSIONS: LPV/SQV/r and high-dose boosted IDV were not well tolerated and led to <65% ITT virological efficacy outcomes. A randomized larger scale study with new formulations and/or more tolerable boosted PIs in NNRTI-based failure is warranted.

Protozoan enteric infection in AIDS related diarrhea in Thailand.

The aim of this study was to determine the prevalence of enteric protozoa and other pathogens in AIDS patients with diarrhea in Bangkok, Thailand. Of 288 consecutive patients screened in the 10 month period between November 1999-August 2000 inclusive, 55 (19.2%) had Cryptosporidium spp, 13 (4.5%) had Isospora oocyst, 11 (3.8%) had Giardia lamblia, 3 (0.9%) had Entamoeba histolytica, and 1 (0.3%) had Iodamoeba butschlii infection. The prevalence of microsporidia was 11% in this study. Of 251 patients for whom stool culture for bacteria was performed, enteric bacterial pathogens isolated were Campylobacter spp in 18 (7.1%), Salmonella spp in 11 (4.3%), and Shigella spp in 1 (0.5%). Other pathogens found in these patients were Clostridium difficile in 16/102 (15.6%). Mycobacterium spp in 18/287 (6.2%), and Strongyloides stercoralis in 23/288 (8.0%). Overall, parasitic and bacterial pathogens were identified in 140 (48.6%) patients. These pathogens were identified by the routine simple wet smear technique in 32, formalin-ether concentration method in 46, culture for S. stercoralis in 5, and culture for bacteria in 30. Additional test, using modified Ziehl-Neelsen staining, identified cryptosporidial oocyst, isospora oocyst, and Mycobacterium spp in 72. The microsporidia, initially identified by modified trichrome blue staining, all were then determined to be Enterocytozoon bieneusi by thin sectioning electron microscopy. Protozoan and bacterial pathogens were confirmed to be important etiologic agents in diarrhea in AIDS in Thailand. They were all associated with increased mortality. Routine stool examination by simple wet smear detected only one-fourth of these pathogens. Therefore all diagnostic techniques for these organisms should be made more widely available in Thailand.