Virologic outcomes of HAART with concurrent use of cytochrome P450 enzyme-inducing antiepileptics: a retrospective case control study

<p>Abstract</p> <p>Background</p> <p>To evaluate the efficacy of highly-active antiretroviral therapy (HAART) in individuals taking cytochrome P450 enzyme-inducing antiepileptics (EI-EADs), we evaluated the virologic response to HAART with or without concurrent antiepileptic use.</p> <p>Methods</p> <p>Participants in the US Military HIV Natural History Study were included if taking HAART for ≥6 months with concurrent use of EI-AEDs phenytoin, carbamazepine, or phenobarbital for ≥28 days. Virologic outcomes were compared to HAART-treated participants taking AEDs that are not CYP450 enzyme-inducing (NEI-AED group) as well as to a matched group of individuals not taking AEDs (non-AED group). For participants with multiple HAART regimens with AED overlap, the first 3 overlaps were studied.</p> <p>Results</p> <p>EI-AED participants (n = 19) had greater virologic failure (62.5%) compared to NEI-AED participants (n = 85; 26.7%) for the first HAART/AED overlap period (OR 4.58 [1.47-14.25]; P = 0.009). Analysis of multiple overlap periods yielded consistent results (OR 4.29 [1.51-12.21]; P = 0.006). Virologic failure was also greater in the EI-AED versus NEI-AED group with multiple HAART/AED overlaps when adjusted for both year of and viral load at HAART initiation (OR 4.19 [1.54-11.44]; P = 0.005). Compared to the non-AED group (n = 190), EI-AED participants had greater virologic failure (62.5% vs. 42.5%; P = 0.134), however this result was only significant when adjusted for viral load at HAART initiation (OR 4.30 [1.02-18.07]; P = 0.046).</p> <p>Conclusions</p> <p>Consistent with data from pharmacokinetic studies demonstrating that EI-AED use may result in subtherapeutic levels of HAART, EI-AED use is associated with greater risk of virologic failure compared to NEI-AEDs when co-administered with HAART. Concurrent use of EI-AEDs and HAART should be avoided when possible.</p

Hepatitis B Vaccine Antibody Response and the Risk of Clinical AIDS or Death

Whether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death. (HR 3.40; 95% CI, 1.39–8.32).

Specific Behaviors Predict \u3ci\u3eStaphylococcus aureus\u3c/i\u3e Colonization and Skin and Soft Tissue Infections Among Human Immunodeficiency Virus- Infected Persons

Background. Few data exist on the incidence and risk factors of Staphylococcus aureus colonization and skin and soft tissue infections (SSTIs) among patients infected with human immunodeficiency virus (HIV). Methods. Over a 2-year period, we prospectively evaluated adults infected with HIV for incident S aureus colonization at 5 body sites and SSTIs. Cox proportional hazard models using time-updated covariates were performed. Results. Three hundred twenty-two participants had a median age of 42 years (interquartile range, 32–49), an HIV duration of 9.4 years (2.7–17.4), and 58% were on highly active antiretroviral therapy (HAART). Overall, 102 patients (32%) became colonized with S aureus with an incidence rate of 20.6 (95% confidence interval [CI], 16.8– 25.0) per 100 person-years [PYs]. Predictors of colonization in the final multivariable model included illicit drug use (hazard ratios [HR], 4.26; 95% CI, 1.33–13.69) and public gym use (HR 1.66, 95% CI, 1.04–2.66), whereas antibacterial soap use was protective (HR, 0.50; 95% CI, 0.32–0.78). In a separate model, perigenital colonization was associated with recent syphilis infection (HR, 4.63; 95% CI, 1.01–21.42). Fifteen percent of participants developed an SSTI (incidence rate of 9.4 cases [95% CI, 6.8–12.7] per 100 PYs). Risk factors for an SSTI included incident S aureus colonization (HR 2.52; 95% CI, 1.35–4.69), public shower use (HR, 2.59; 95% CI, 1.48–4.56), and hospitalization (HR 3.54; 95% CI, 1.67–7.53). The perigenital location for S aureus colonization was predictive of SSTIs. Human immunodeficiency virus-related factors (CD4 count, HIV RNA level, and HAART) were not associated with colonization or SSTIs. Conclusions. Specific behaviors, but not HIV-related factors, are predictors of colonization and SSTIs. Behavioral modifications may be the most important strategies in preventing S aureus colonization and SSTIs among persons infected with HIV

Detecting Rickettsia parkeri Infection from Eschar Swab Specimens

The typical clinical presentation of several spotted fever group Rickettsia infections includes eschars. Clinical diagnosis of the condition is usually made by analysis of blood samples. We describe a more sensitive, noninvasive means of obtaining a sample for diagnosis by using an eschar swab specimen from patients infected with Rickettsia parkeri

Analysis of the Impact of Early Surgery on In-Hospital Mortality of Native Valve Endocarditis

Background— The impact of early surgery on mortality in patients with native valve endocarditis (NVE) is unresolved. This study sought to evaluate valve surgery compared with medical therapy for NVE and to identify characteristics of patients who are most likely to benefit from early surgery. Methods and Results— Using a prospective, multinational cohort of patients with definite NVE, the effect of early surgery on in-hospital mortality was assessed by propensity-based matching adjustment for survivor bias and by instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection, and congestive heart failure. Of the 1552 patients with NVE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared with medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] versus 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction [ARR] −5.9%, P<0.001). With a combined instrument, the instrumental-variable–adjusted ARR in mortality associated with early surgery was −11.2% (P<0.001). In subgroup analysis, surgery was found to confer a survival benefit compared with medical therapy among patients with a higher propensity for surgery (ARR −10.9% for quintiles 4 and 5, P=0.002) and those with paravalvular complications (ARR −17.3%, P<0.001), systemic embolization (ARR −12.9%, P=0.002), S aureus NVE (ARR −20.1%, P<0.001), and stroke (ARR −13%, P=0.02) but not those with valve perforation or congestive heart failure. Conclusions— Early surgery for NVE is associated with an in-hospital mortality benefit compared with medical therapy alone