Ototoxic reactions of quinine in healthy persons and patients with Plasmodium falciparum infection

Audiometric changes following quinine administration were studied in healthy Caucasian subjects and patients suffering from falciparum malaria disease. Quinine-dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 h every 8 h in 10 Plasmodium falciparum malaria patients. The hearing function was monitored by conventional and high frequency audiometry. In nine healthy subjects hearing loss was documented at 2-4 h after infusion of Quinine-dihydrochloride at a mean maximal plasma quinine concentration of only 2 mg/l. In one healthy subject a persistent loss occurred of 20 dB at 14 kHz in one ear. In all malaria patients severe hearing losses and adverse effects related to ototoxicity were documented, but all the audiograms had returned to normal after 1 week and side effects disappeared. This study has shown that ototoxicity induced by quinine is almost completely reversible in healthy volunteers and in malaria patient

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Comparison of Two HIV Postexposure Prophylaxis Regimens Among Men Who Have Sex With Men in Amsterdam: Adverse Effects Do Not Influence Compliance

To compare 2 regimens for HIV postexposure prophylaxis (PEP) as to safety, adherence, outcome, and follow-up in men who have sex with men (MSM) in Amsterdam. Since 2000, all MSM starting HIV PEP in Amsterdam have been followed in 1 location. The regimen was comprised of zidovudine or lamivudine and nelfinavir (regimen 1) until 2005, when nelfinavir was replaced by atazanavir (regimen 2). All patient data, including data on PEP side effects and testing for alanine aminotransferase (ALT), were systematically recorded and compared between the 2 regimens from 2000 to 2007. HIV PEP was prescribed 309 times to MSM. Of the 261 who were followed up, 237 (91%) completed their 28-day course. Although fewer patients had diarrhea on regimen 2 than on regimen 1 (P = 0.00), the proportion completing either course was the same: 98 of 110 (89%) and 139 of 151 (92%), respectively (P = 0.42). Only 1 patient with severely elevated ALT was advised to stop PEP, he also had serious illness. MSM at least 30 years of age and MSM who had sex with a partner known to be HIV-positive completed their course significantly more often than those under 30 and those who had sex with a partner of unknown HIV status (P <0.005). Of MSM who completed PEP, 5 seroconverted for HIV despite good adherence to PEP. None of their viruses were resistant to the PEP regimen used. No difference in adherence was found between the 2 regimens, even though fewer adverse effects were reported on regimen 2. ALT need not be routinely tested to monitor adverse effects. The 5 seroconversions were not likely caused by PEP failure, but rather by ongoing HIV exposure

Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis. Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting. Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis. Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries. © 2014 Wolters Kluwer Health | Lippincott Williams &amp; Wilkins