Deborah Konopnicki

Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort

Background: Whether hepatitis B (HBV) coinfection affects outcome in HIV-1-infected patients remains unclear. Objective: To assess the prevalence of HBV (assessed as HBsAg) coinfection and its possible impact on progression to AIDS, all-cause deaths, liver-related deaths and response to highly active antiretroviral therapy (HAART) in the EuroSIDA cohort. Methods: Data on 9802 patients in 72 European HIV centres were analysed. Incidence rates of AIDS, global mortality and liver-related mortality, time to 25% CD4 cell count increase and time to viral load < 400 copies/ml after starting HAART were calculated and compared between HBsAg-positive and HBsAg-negative patients. Results: HBsAg was found in 498 (8.7%) patients. The incidence of new AIDS diagnosis was similar in HBsAg-positive and HBsAg-negative patients (3.3 and 3.4/100 person-years, respectively) even after adjustment for potential confounders: the incidence rate ratio (IRR) was 0.94 [95% confidence interval (CI), 0.74–1.19; P = 0.61]. The incidences of all-cause and liver-related mortalities were significantly higher in HBsAg-positive subjects (3.7 and 0.7/100 person-years, respectively) compared with HBsAg-negative subjects (2.6 and 0.2/100 person-years, respectively). The adjusted IRR values were 1.53 for global (95% CI, 1.23–1.90; P = 0.0001) and 3.58 for liver-related (95% CI, 2.09–6.16; P < 0.0001) mortality. HBsAg status did not influence viral or immunological responses among the 1679 patients starting HAART. Conclusions: The prevalence of HBV coinfection was 9% in the EuroSIDA cohort. Chronic HBV infection significantly increased liver-related mortality in HIV-1-infected patients but did not impact on progression to AIDS or on viral and immunological responses to HAART.

Indinavir/ritonavir‐based therapy in HIV‐1‐infected antiretroviral therapy‐naive patients: comparison of 800/100 mg and 400/100 mg twice daily

To compare the efficacy and tolerability of indinavir (IDV)/ritonavir (RTV) at 800/100 and 400/100 mg twice daily (bid) in antiretroviral therapy (ART)‐naive patients.

Impact of rapid microbial identification directly from positive blood cultures using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry on patient management

For septic patients, delaying the initiation of antimicrobial therapy or choosing an inappropriate antibiotic can considerably worsen their prognosis. This study evaluated the impact of rapid microbial identification (RMI) from positive blood cultures on the management of patients with suspected sepsis. During a 6-month period, RMI by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed for all new episodes of bacteraemia. For each patient, the infectious disease specialist was contacted and questioned about his therapeutic decisions made based on the Gram staining and the RMI. This information was collected to evaluate the number of RMIs that led to a therapeutic change or to a modification of the patients general management (e.g. fast removal of infected catheters). During the study period, 277 new episodes of bacteraemia were recorded. In 71.12% of the cases, MALDI-TOF MS resulted in a successful RMI (197/277). For adult and paediatric patients, 13.38% (21/157) and 2.50% (1/40) of the RMIs, respectively, resulted in modification of the treatment regimen, according to the survey. In many other cases, the MALDI-TOF MS was a helpful tool for infectious disease specialists because it confirmed suspected cases of contamination, especially in the paediatric population (15/40 RMIs, 37.50%), or suggested complementary diagnostic testing. This study emphasizes the benefits of RMI from positive blood cultures. Although the use of this technique represents an extra cost for the laboratory, RMI using MALDI-TOF MS has been implemented in our daily practice.

Sustained Viral Suppression and Higher CD4+ T-Cell Count Reduces the Risk of Persistent Cervical High-Risk Human Papillomavirus Infection in HIV-Positive Women

BACKGROUND Studies analyzing the impact of combination antiretroviral therapy (cART) on cervical infection with high-risk human papillomavirus (HR-HPV) have generated conflicting results. We assessed the long-term impact of cART on persistent cervical HR-HPV infection in a very large cohort of 652 women who underwent follow-up of HIV infection for a median duration of 104 months. METHODS Prospective cohort of HIV-infected women undergoing HIV infection follow-up who had HR-HPV screening and cytology by Papanicolaou smear performed yearly between 2002 and 2011. RESULTS At baseline, the median age was 38 years, the race/ethnic origin was sub-Sarahan Africa for 84%, the median CD4(+) T-cell count was 426 cells/µL, 79% were receiving cART, and the HR-HPV prevalence was 43%. The median interval of having had an HIV load of <50 copies/mL was 40.6 months at the time of a HR-HPV-negative test result, compared with 17 months at the time of a HR-HPV-positive test result (P < .0001, by univariate analysis). The median interval of having had a CD4(+) T-cell count of >500 cells/µL was 18.4 months at the time of a HR-HPV-negative test result, compared with 4.45 months at the time of a HR-HPV-positive test result (P < .0001). In multivariate analysis, having had an HIV load of <50 copies/mL for >40 months (odds ratio [OR], 0.81; 95% confidence interval [CI], .76-.86; P < .0001) and having had a CD4(+) T-cell count of >500 cells/µL for >18 months (OR, 0.88; 95% CI, .82-.94; P = .0002) were associated with a significantly decreased risk of HR-HPV infection. CONCLUSION Sustained HIV suppression for >40 months and a sustained CD4(+) T-cell count of >500 cells/µL for >18 months are independently and significantly associated with a decreased risk of persistent cervical HR-HPV infection.

High-risk human papillomavirus infection in HIV-positive African women living in Europe

Cervical infection with high‐risk human papillomavirus (HRHPV) induces cervical cancer and is present in 14% of women in Europe. We assessed the prevalence and incidence of cervical HRHPV in a cohort of HIV‐positive women living in Belgium.

Prolonged antiretroviral therapy is associated with fewer anal high-grade squamous intraepithelial lesions in HIV-positive MSM in a cross-sectional study

Objective HIV-positive men who have sex with men (MSM) are at increased risk of anal cancer. We evaluate the risk factors for anal high-grade squamous intraepithelial lesion (HSIL) (the precursor of anal cancer) in HIV-positive MSM. Methods In this cross-sectional study within a cohort, 320 HIV-positive MSM were screened by anal cytology followed by high-resolution anoscopy (HRA) in case of abnormal cytology. Risk factors for anal HSIL were analysed. Results Men were mostly middle-aged Caucasians with median CD4+ T lymphocytes of 638 cells/µL, 87% on combined antiretroviral therapy (cART) for a median of 5 years. 198 anal cytology samples were normal. In the 122 patients with abnormal cytology, HRA with biopsies were performed: 12% (n=15) normal, 36% (n=44) anal low-grade squamous intraepithelial lesion (LSIL) and 51% (n=63) anal HSIL. Comparing patients with or without anal HSIL (normal cytology or normal biopsy or LSIL), we found in multivariate analysis significantly fewer anal HSIL in patients with cART ≥24 months (OR 0.32 CI 95% 0.162 to 0.631, p=0.001). Conclusions Prolonged cART (≥24 months) is associated with fewer anal HSIL.

High-risk human papillomavirus genotypes distribution in a cohort of HIV-positive women living in Europe: epidemiological implication for vaccination against human papillomavirus.

Background:Worldwide, human papillomavirus (HPV) 16 and 18 represents 70% of high-risk (HR) HPV found in cervical cancer. However HIV-positive women are more frequently infected by HRHPV other than HPV 16 or 18 (OHR). We aimed to analyse the HRHPV genotype distribution in a cohort of HIV-positive women and to estimate the potential protection offered by the different HPV vaccines. Methods:HRHPV genotypes by PCR and cytology were assessed in cervical samples from 508 HIV-positive women prospectively followed in Brussels. Results:Women characteristics were as follows: African origin (84%), median age 42 years, median CD4+ T 555/&mgr;l, 89% under combined antiretroviral therapy and 73% with HIVRNA less than 20 copies/ml. HRHPV prevalence was 23% (116/508): 38% had abnormal cytology, 76% carried OHR without HPV 16 or 18 and 11% had concomitant infection by OHR and HPV 16 or 18. The most frequent HRHPV were HPV52 (19.8%), HPV18 (14.6%), HPV31/35/51/58 (12.1% each), HPV56 (9.9%) and HPV16 (9.5%). Less than 30% of women had their HRHPV genotypes included in the bivalent or quadrivalent vaccines against HRHPV 16 and 18; however, 79% had their HRHPV covered by the ninevalent vaccine against HRHPV 16/18/31/33/45/52/58. Conclusion:The HRHPV genotypes distribution found in these women living in Europe with a successfully treated HIV is similar to the one found in Central Africa with HRHPV other than HPV16 or 18 retrieved in 87%. In this population, the bivalent or quadrivalent vaccines could offer protection in only 30% of women; however this protection could be extended up to 80% with the ninevalent vaccine.

MALDI-TOF MS contribution to the diagnosis of Campylobacter rectus multiple skull base and brain abscesses

Campylobacter rectus is rarely associated with invasive infection. Both the isolation and the identification requirements of C. rectus are fastidious, probably contributing to an underestimation of its burden. We report the case of a 66-year-old man who developed several skull base and intracerebral abscesses after dental intervention. Campylobacter rectus was isolated from the brain biopsy. Within 45 minutes of reading the bacterial plate, the strain was accurately identified by MALDI-TOF MS. This rapid identification avoided the extra costs and delays present with 16S rRNA gene sequencing and allowed for a rapid confirmation of the adequacy of the empirical antibiotic treatment.

Lowered Rilpivirine Exposure During the Third Trimester of Pregnancy in Human Immunodeficiency Virus Type 1-Infected Women

Background The use of antiretroviral therapy during pregnancy is important for control of maternal human immunodeficiency virus (HIV) disease and the prevention of perinatal HIV transmission. Physiological changes during pregnancy can reduce antiretroviral exposure. We studied the pharmacokinetics of rilpivirine 25 mg once daily in HIV-1-infected women during late pregnancy. Methods We conducted a nonrandomized, open-label, multicenter, phase 4 study. HIV-infected pregnant women receiving rilpivirine 25 mg once daily were included. Intensive 24-hour pharmacokinetic sampling was performed in the third trimester and at least 2 weeks postpartum. Pharmacokinetic parameters were calculated by noncompartmental analysis. Results Sixteen subjects were included. Geometric mean ratios of third trimester vs postpartum were 0.55 (90% confidence interval [CI], .46-.66) for the 24-hour area under the concentration-time curve (AUC0-24h); 0.65 (90% CI, .55-.76) for the maximum concentration; and 0.51 (90% CI, .41-.63) for the minimum observed concentration (Cmin). Four of 16 (25%) subjects had Cmin below the target concentration (0.04 mg/L) in the third trimester of pregnancy. No subtherapeutic levels were observed postpartum. No detectable viral loads were observed in this study. All newborns tested negative for HIV. No birth defects were reported. The median (range, n = 5) rilpivirine cord-to-maternal plasma concentration ratio was 0.50 (range, .35-.81). Conclusions Rilpivirine exposure is substantially lowered during late pregnancy. Despite lower exposure, virologic suppression was maintained and no perinatal transmission was observed. Overall, these results suggest that rilpivirine 25 mg once daily may be an alternative treatment option for HIV-1-infected pregnant women who are virologically suppressed, in settings where therapeutic drug monitoring and/or close viral load monitoring are feasible to detect suboptimal antiretroviral therapy. Clinical Trials Registration NCT00825929.

Relapsing fever in asylum seekers from Somalia arriving in Belgium in August 2015.

Current population displacements favor the re-emerging of diseases, nowadays very rare in Europe. We report two cases of ‘imported’ relapsing fever in two Somali asylum seekers occurring shortly after their arrival in Belgium. A diagnosis of relapsing fever should be considered in all migrants coming from endemic regions or having traveled in low hygiene and crowded conditions, presenting with recurrent fever, especially if no malaria parasites are found.