Risk factors for and outcome of hyperlactatemia in HIV-infected persons: is there a need for routine lactate monitoring?

BACKGROUND: Lactic acidosis is a rare but life-threatening complication of combination antiretroviral therapy (CART). Asymptomatic or mildly symptomatic episodes of hyperlactatemia are more frequent, but their clinical relevance is unknown. METHODS: The incidences of, risk factors for, and courses of hyperlactatemia and lactic acidosis were prospectively assessed in the following 3 groups at the Zurich center of the Swiss HIV Cohort Study: persons already receiving CART at baseline, treatment-naive persons who initiated CART during the observation period, and persons who received no CART before or during the observation period. RESULTS: During 4788 person-years of follow-up, a total of 22,678 lactate assessments were performed for 1566 persons; 662 (42.3%) had at least 1 lactate level measurement of > 2.4 mmol/L, and 49 (3.1%) had severe hyperlactatemia (lactate level of > 5.0 mmol/L). The incidence of hyperlactatemia was 227 cases (95% confidence interval [CI], 210-245) and 59 cases (95% CI, 38-93) per 1000 person-years of follow-up among persons with and persons without CART, respectively. During the observation period, the incidence decreased from 459 cases (95% CI, 415-508) to 85 cases (95% CI, 76-107) per 1000 person-years of follow-up, respectively, because of changing CART prescription patterns. Severe hyperlactatemia occurred in treated persons only. In multivariable Cox proportional hazards models, significant risk factors for severe hyperlactatemia were regimens containing stavudine and didanosine (hazard ratio [HR], 6.65; 95% CI, 2.70-16.3) and regimens containing efavirenz (HR, 2.85; 95% CI, 1.31-6.21). Lactic acidosis was diagnosed in 4 of 1566 persons, all of whom were receiving stavudine and didanosine. CONCLUSIONS: Hyperlactatemia was frequently observed in all 3 groups, but severe hyperlactatemia and lactic acidosis were rarely observed among persons who received CART. Lactate monitoring appears to be indicated primarily for persons receiving stavudine and didanosine and for persons who are symptomatic. Long-term follow-up is needed to investigate the risk of novel treatment regimens for hyperlactatemia.

Impact of genotypic resistance testing on selection of salvage regimen in clinical practice.

OBJECTIVE: To determine whether genotypic resistance testing leads to selection of more potent drug regimens when compared to regimens based on treatment history only. DESIGN: Prospective, tertiary care centre-based study. PATIENTS: One-hundred-and-forty-five HIV-infected adults on stable antiretroviral therapy (ART) for >6 months experiencing virological failure. METHODS: The physicians' decision-making process when choosing a salvage regimen was prospectively documented: at time of virological failure, on 'failing ART', genotyping was performed and a hypothetical 'clinical expert ART' based upon patient's drug history was documented. Subsequently, data on resistance mutations, rating by a decision support software and drug history were used to define 'genotyping ART'. After discussion with the patient, final treatment, 'new personalized ART' was chosen and prescribed. To compare the relative potency of the four ART regimens in a standardized manner, a resistance score ranging from 1 (best) to 8 (worst) based on drug ranking by decision support software was attributed to each ART regimen. Virological and immunological outcomes were analysed based on the magnitude of the resistance score. RESULTS: Median follow-up was 1.5 years. In all 145 patients, median resistance scores for the stepwise selected ART regimens were: 'failing ART': 4.5, 'clinical expert ART': 1.8, 'genotyping ART': 1.5 and 'new personalized ART': 2. The latter was 1.5 in patients who effectively switched to 'new personalized ART' (n=89). Lower resistance scores translated into significantly improved virological response after initiation of 'new personalized ART'. In multivariable analysis, lower resistance scores, lower baseline HIV RNA levels and use of novel antiretroviral drugs were associated with the probability of reducing plasma viraemia to <50 copies/ml. CONCLUSIONS: This study suggests that treatment choices including genotype and decision support software were virologically superior to those based on drug history only.

Clonal spread of mef-positive macrolide-resistant Streptococcus pneumoniae isolates causing invasive disease in adults in Germany.

Isolates (3,845) obtained from German adults with invasive pneumococcal disease between 1992 and 2004 were investigated. Of these, 430 isolates (11.2%) were erythromycin A nonsusceptible. Macrolide resistance genotypes and multilocus sequence types were determined. Among the isolates, 35.6% were erm(B) positive and 63.5% were mef positive. Over the study period, the frequency of resistance rose significantly from 2.2 to 17.0% (P < 0.001). A serotype 14, sequence type 9 clone was the most widespread.

Emergence of macrolide and penicillin resistance among invasive pneumococcal isolates in Germany.

Continuous nationwide surveillance of antibiotic resistance in invasive pneumococcal disease was performed in Germany between 1992 and 2000, with a total of 2586 strains being isolated. The average resistance rates to erythromycin and clindamycin were 7.7% and 3.5%, respectively, throughout the study period; 3.3% of strains were found to have intermediate resistance to penicillin. Over the study period an increase in both macrolide and penicillin resistance was observed. The percentage of strains exhibiting reduced susceptibility to penicillin increased from 1.8% in 1992 to 5.8% in 2000. A dramatic increase in resistance was observed with erythromycin, where the resistance rate rose from 3.0% in 1992 to 15.3% in 2000. Of the erythromycin-resistant strains, 86 (43.4%) and 111 (56.1%) belonged to the erm(B) and mef types of resistance, respectively. An analysis of macrolide consumption data during the study period showed that erythromycin resistance was highly correlated to the consumption of newer bd and od macrolides (r = 0.89, P < 0.01).