Transmitted Raltegravir Resistance in An HIV-1 Crf_Ag-Infected PatientBoyd, Sarita D; Maldarelli, Frank; Sereti, Irini; Ouedraogo, G Laissa; Rehm, Catherine A; Boltz, Valerie; Shoemaker, Diana; Pau, Alice K
doi: 10.3851/imp1749pmid: 21447876
Abstract Here, we describe an HIV-infected patient with pre-treatment resistance to raltegravir, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the ultimate ability to achieve viral suppression. Pretreatment integrase resistance testing is not routinely performed because transmitted integrase mutations conferring resistance to raltegravir are currently thought to be negligible. We suggest obtaining a pretreatment integrase genotype in patients with transmitted multiclass drug resistance in order to create an optimal first regimen and increase the chance for virological suppression.
Risk Factors for Fatality in HIV-Infected Patients with Dideoxynucleoside-Induced Severe Hyperlactataemia or Lactic AcidosisGroup, the Lactic Acidosis International Study; Arenas-Pinto, Alejandro; Grant, Alison; Bhaskaran, Krishnan; Copas, Andrew; Carr, Andrew; Worm, Signe W; Martinez, Esteban; Reiss, Peter; Dunn, David; Weber, Rainer; Hoy, Jennifer; Weller, Ian
doi: 10.3851/imp1739pmid: 21447871
Abstract Background Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate. Methods In a multinational retrospective cohort study, LA was defined as arterial blood pH<7.35, bicarbonate <20 mmol/l and lactate above normal, and HL as con-firmed blood lactate >5 mmol/l. Logistic regression was used to identify factors associated with fatality. Sensitivity and specificity of different case definitions as predictors of death were compared. Results The overall case-fatality rate was 19/110 (17.3%), but among acidotic patients it was 33% (16/49 cases). There were 10 asymptomatic patients and none of them died as a consequence of the event. The median lactate for fatal, non-fatal and all patients was 8.3 mmol/l (IQR 7.2–13.1), 6.4 mmol/l (IQR 5.4–7.8) and 6.7 mmol/l (IQR 5.5–8.1), respectively. After adjusting for age and current CD4+ T-cell count, lactate >7 mmol/l (OR 6.27, 95% CI 1.13–34.93), blood bicarbonate <12 mmol/l (OR 10.02 relative to >18 mmol/l, 95% CI 1.33–75.65) and concurrent opportunistic infections (OR 8.69, 95% CI 1.45–52.22) were independently associated with case fatality. Blood lactate >7 mmol/l showed a sensitivity of 84% for fatality with a specificity of 60%, whereas bicarbonate <12 mmol/l showed a better specificity (85%) but a poorer sensitivity (42%). Bicarbonate <18 mmol/l appears to be as good as lactate <7 mmol/l at predicting death (sensitivity 90% and specificity 54%). Conclusions Our data suggest that blood lactate >7 mmol/l and blood bicarbonate <18 mmol/l appear to predict death and might help clinicians in selecting patients who may benefit from more intense monitoring.
On-Treatment Monitoring of Liver Fibrosis with Transient Elastography in Chronic Hepatitis B PatientsWong, Grace Lai-Hung; Wong, Vincent Wai-Sun; Choi, Paul Cheung-Lung; Chan, Anthony Wing-Hung; Chim, Angel Mei-Ling; Yiu, Karen Ka-Lam; Chu, Shirley Hoi-Ting; Chan, Francis Ka-Leung; Sung, Joseph Jao-Yao; Chan, Henry Lik-Yuen
doi: 10.3851/imp1726pmid: 21447865
Abstract Background The performance of liver stiffness measurement (LSM) to monitor the changes in the severity of liver fibrosis in chronic hepatitis B (CHB) patients on antiviral treatment is uncertain. Methods We prospectively studied CHB patients undergoing paired liver biopsy and transient elastography before and at week 48 of antiviral treatment. Based on our previously reported LSM algorithm, advanced liver fibrosis (F3–4) could be excluded or confirmed at >90% confidence. Results A total of 71 CHB patients were studied. The median alanine aminotransferase (ALT) level decreased from 99I U/l to 33I U/l, and the median LSM decreased from 8.8 kPa to 6.6 kPa, respectively, from baseline to week 48. Overall, 17 and 11 patients had regression and progression of histological fibrosis, respectively. Areas under the receiver operating characteristics curves of the LSM algorithm at baseline and week 48 for advanced fibrosis were 0.80 (95% confidence interval [CI] 0.69– 0.90) and 0.78 (95% CI 0.64–0.92), respectively. The sensitivity of LSM algorithm to exclude advanced fibrosis was 100% at baseline and 75% at week 48. The specif-city of the LSM algorithm to diagnose advanced fibrosis was 84% at baseline and 91% at week 48. Overall, 11/28 (39%) patients with LSM that decreased by >30%, 28/41 (68%) of patients with LSM that changed within 30% and 1/2 (50%) patients with LSM that increased by >30% had decreased, unchanged and increased histological fibrosis stages, respectively. Conclusions LSM could predict advanced fibrosis during antiviral therapy according to the ALT-based algorithm. Decrease in absolute LSM value, which could be related to ALT normalization, was unreliable to indicate regression of liver fibrosis.