Antiretroviral therapy of late presenters with advanced HIV disease

Potent antiretroviral therapy (ART) has dramatically improved the prognosis of HIV-1-infected individuals. However, 10% to 30% of patients in Western countries still present late for care, when CD4 T cells are below 200 cells/mm3 and symptomatic HIV disease has occurred. Clinical considerations for advanced HIV disease are paramount as morbidity and mortality are directly correlated with a low initial CD4 T cell count, which is commonly associated with the simultaneous occurrence of co-morbidities, particularly opportunistic infections. Upon start of ART, the clinical entity of immune reconstitution inflammatory syndrome may occur and, in this context, raise the question of early versus delayed ART in patients treated for opportunistic infections. Recent data clearly indicate that an earlier start of ART is warranted in this latter situation. Guidelines for specific antiretroviral treatment for late-presenting patients are lacking. Knowledge about drug-drug interactions and co-morbidities should guide treatment choices and influence the clinical management and monitoring of drug-related side effects and interactions. Importantly, the outlook of patients who present late is very much dependent upon the initial response to ART. Nevertheless, even if optimal response to treatment has been achieved, long-term prognosis may be impaired in patients who initially presented with advanced HIV disease. We encourage physicians to perform HIV testing more frequently in order to detect HIV-infected individuals in tim

Additive Effect of Enterococcus faecium on Enterococcal Bloodstream Infections: A 14-Year Study in a Swiss Tertiary Hospital

We investigated whether an increase in enterococcal bloodstream infections (BSIs) depends on the emergence of Enterococcus faecium in an area with low vancomycin-resistant enterococci prevalence. From 1999 to 2012, a linear increase in E. faecium BSI rates (0.009 per 1,000 patient-days per year; P<.001) was noted. Enterococcus faecalis BSI rates remained stabl

A rifampicin-containing antibiotic treatment improves outcome of staphylococcal deep sternal wound infections

Background Deep sternal wound infection (DSWI) is a severe complication after cardiac surgery, mostly caused by staphylococci. Little is known about the optimal antibiotic management. Methods A 10 year retrospective analysis of 100 patients with staphylococcal DSWI after cardiac surgery in a tertiary hospital. Treatment failure was defined as sternal wound dehiscence or fistula at the end of the prescribed antibiotic therapy, 12 months later, or DSWI-related death. Results Most patients were male (83%) and the median age was 72 years [interquartile range (IQR) 63-76]. Coronary artery bypass was the most frequent preceding procedure (93%). The median time to diagnosis of DSWI was 13 days (IQR 10-18) after surgery. Clinical presentation consisted of wound discharge in 77% of patients. Coagulase-negative staphylococci were isolated in 54 and Staphylococcus aureus in 46 patients. All patients received antibiotics and 95% underwent surgical debridement. The median duration of antibiotic treatment was 47 days (IQR 41-78). During follow-up, 21 out of 100 patients experienced treatment failure. Of these, 8/21 patients (38%) died from DSWI after a median of 12 days (IQR 8-30). In the multivariate analysis, a rifampicin-containing antibiotic regimen was the only factor associated with lower risk of treatment failure (hazard ratio 0.26, 95% confidence interval 0.10-0.64, P = 0.004). Prolonged treatment (12 weeks instead of 6 weeks) did not alter outcome (P = 0.716) in patients without prosthetic valve endocarditis. Conclusions Treatment of rifampicin-susceptible staphylococcal DSWI with a rifampicin-containing antibiotic regimen may improve the outcome. After surgical debridement an antibiotic treatment of 6 weeks may be adequate for staphylococcal DSW

Adverse events of raltegravir and dolutegravir.

To compare the frequency and risk factors of toxicity-related treatment discontinuations between raltegravir and dolutegravir. Prospective cohort study. All antiretroviral therapy (ART)-naïve and ART-experienced HIV-infected individuals from the Swiss HIV Cohort Study who initiated raltegravir or dolutegravir between 2006 and 2015 were investigated concerning treatment modification within the first year. Of 4041 patients initiating ART containing raltegravir (n = 2091) or dolutegravir (n = 1950), 568 patients discontinued ART during the first year, corresponding to a rate of 15.5 [95% confidence interval (CI) 14.5-16.9] discontinuations per 100 patient-years. Only 10 patients on raltegravir (0.5%) and two patients on dolutegravir (0.1%) demonstrated virologic failure. The main reason for ART discontinuation was convenience expressed as patient's wish, physician's decision, or treatment simplification (n = 302). Toxicity occurred in 4.3% of patients treated with raltegravir and 3.6% with dolutegravir, respectively. In multivariable analysis, the only independent risk factor for discontinuing ART because of toxicity was female sex (hazard ratio 1.98, 95% CI 1.45-2.71, P &lt; 0.001).Neuropsychiatric complaints were the most commonly reported toxic adverse events and more frequent in the dolutegravir (n = 33, 1.7%) compared with the raltegravir group (n = 13, 0.6%). Risk of discontinuation for neurotoxicity was lower for raltegravir than for dolutegravir in multivariable analysis (hazard ratio 0.46, 95% CI 0.22-0.96, P = 0.037). In this, large cohort raltegravir and dolutegravir-containing regimen demonstrated a high virologic efficacy. Drug toxicity was infrequent and discontinuation because of neuropsychiatric events within the first year of treatment was only marginal higher with dolutegravir compared with raltegravir. However, monitoring of neurotoxic side-effects of dolutegravir is important

Improved sensitivity of an interferon-gamma release assay (T-SPOT.TB™) in combination with tuberculin skin test for the diagnosis of latent tuberculosis in the presence of HIV co-Infection

BACKGROUND: Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV infection. METHODS: IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture-confirmed tuberculosis was diagnosed in HIV-infected individuals in the Swiss HIV Cohort Study. RESULTS: 64 individuals (69% males, 45% of non-white ethnicity, median age 35 years (interquartile range [IQR] 31-42), 28% with prior AIDS) were analysed. Median CD4 cell count was 223 cells/μl (IQR 103-339), HIV-RNA was 4.7 log10 copies/mL (IQR 4.3-5.2). T-SPOT.TB resulted positive in 25 patients (39%), negative in 18 (28%) and indeterminate in 21 (33%), corresponding to a sensitivity of 39% (95% CI 27-51%) if all test results were considered, and 58% (95% CI 43-74%) if indeterminate results were excluded. Sensitivity of IGRA was independent of CD4 cell count (p = 0.698). Among 44 individuals with available TST, 22 (50%) had a positive TST. Agreement between TST and IGRA was 57% (kappa = 0.14, p = 0.177), and in 34% (10/29) both tests were positive. Combining TST and IGRA (at least one test positive) resulted in an improved sensitivity of 67% (95% CI 52-81%). In multivariate analysis, older age was associated with negative results of TST and T-SPOT.TB (OR 3.07, 95% CI 1,22-7.74, p = 0.017, per 10 years older). CONCLUSIONS: T-SPOT.TB and TST have similar sensitivity to detect latent TB in HIV-infected individuals. Combining TST and IGRA may help clinicians to better select HIV-infected individuals with latent tuberculosis who qualify for preventive treatment

Factors Associated with the Incidence of Type 2 Diabetes Mellitus in HIV-Infected Participants in the Swiss HIV Cohort Study

Background. Human immunodeficiency virus (HIV)-infected persons may be at increased risk for developing type 2 diabetes mellitus because of viral coinfection and adverse effects of treatment. Methods. We studied associations of new-onset diabetes mellitus with hepatitis B virus and hepatitis C virus coinfections and antiretroviral therapy in participants in the Swiss HIV Cohort Study, using Poisson regression. Results. A total of 123 of 6513 persons experienced diabetes mellitus during 27,798 person-years of follow-up (PYFU), resulting in an incidence of 4.4 cases per 1000 PYFU (95% confidence interval [CI], 3.7-5.3 cases per 1000 PYFU). An increased incidence rate ratio (IRR) was found for male subjects (IRR, 2.5; 95% CI, 1.5-4.2), older age (IRR for subjects >60 years old, 4.3; 95% CI, 2.3-8.2), black (IRR, 2.1; 95% CI, 1.1-4.0) and Asian (IRR, 4.9; 95% CI, 2.2-10.9) ethnicity, Centers for Disease Control and Prevention disease stage C (IRR, 1.6; 95% CI, 1.04-2.4), and obesity (IRR, 4.7; 95% CI, 3.1-7.0), but results for hepatitis C virus infection or active hepatitis B virus infection were inconclusive. Strong associations were found for current treatment with nucleoside reverse-transcriptase inhibitors (IRR, 2.22; 95% CI, 1.11-4.45), nucleoside reverse-transcriptase inhibitors plus protease inhibitors (IRR, 2.48; 95% CI, 1.42-4.31), and nucleoside reverse-transcriptase inhibitors plus protease inhibitors and nonnucleoside reverse-transcriptase inhibitors (IRR, 3.25; 95% CI, 1.59-6.67) but were not found for treatment with nucleoside reverse-transcriptase inhibitors plus nonnucleoside reverse-transcriptase inhibitors (IRR, 1.47; 95% CI, 0.77-2.82). Conclusions. In addition to traditional risk factors, current treatment with protease inhibitor- and nucleoside reverse-transcriptase inhibitor-containing regimens was associated with the risk of developing type 2 diabetes mellitus. Our study did not find a significant association between viral hepatitis infection and risk of incident diabete

Incidence and Outcome of Progressive Multifocal Leukoencephalopathy over 20 Years of the Swiss HIV Cohort Study

Background. We investigated the incidence and outcome of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected individuals before and after the introduction of combination antiretroviral therapy (cART) in 1996. Methods. From 1988 through 2007, 226 cases of PML were reported to the Swiss HIV Cohort Study. By chart review, we confirmed 186 cases and recorded all-cause and PML-attributable mortality. For the survival analysis, 25 patients with postmortem diagnosis and 2 without CD4+ T cell counts were excluded, leaving a total of 159 patients (89 before 1996 and 70 during 1996-2007). Results. The incidence rate of PML decreased from 0.24 cases per 100 patient-years (PY; 95% confidence interval [CI], 0.20-0.29 cases per 100 PY) before 1996 to 0.06 cases per 100 PY (95% CI, 0.04-0.10 cases per 100 PY) from 1996 onward. Patients who received a diagnosis before 1996 had a higher frequency of prior acquired immunodeficiency syndrome-defining conditions (P=.007) but similar CD4+ T cell counts (60 vs. 71 cells/µL; P=.25), compared with patients who received a diagnosis during 1996 or thereafter. The median time to PML-attributable death was 71 days (interquartile range, 44-140 days), compared with 90 days (interquartile range, 54-313 days) for all-cause mortality. The PML-attributable 1-year mortality rate decreased from 82.3 cases per 100 PY (95% CI, 58.8-115.1 cases per 100 PY) during the pre-cART era to 37.6 cases per 100 PY (95% CI, 23.4.-60.5 cases per 100 PY) during the cART era. In multivariate models, cART was the only factor associated with lower PML-attributable mortality (hazard ratio, 0.18; 95% CI, 0.07-0.50; P<.001), whereas all-cause mortality was associated with baseline CD4+ T cell count (hazard ratio per increase of 100 cells/µL, 0.52; 95% CI, 0.32-0.85; P=.010) and cART use (hazard ratio, 0.37; 95% CI, 0.19-0.75; P=.006). Conclusions. cART reduced the incidence and PML-attributable 1-year mortality, regardless of baseline CD4+ T cell count, whereas overall mortality was dependant on cART use and baseline CD4+ T cell coun