Hepatitis C virus coinfection does not influence the CD4 cell recovery in HIV-1-infected patients with maximum virologic suppression.

BACKGROUND: Conflicting data exist whether hepatitis C virus (HCV) affects the CD4 cell recovery in patients with HIV starting antiretroviral treatment. OBJECTIVE: To investigate the influence of HCV coinfection on the CD4 recovery in patients with maximum virologic suppression within the EuroSIDA cohort. METHODS: Patients tested for anti-HCV antibodies and with at least 2 consecutive HIV viral loads (VLs) <50 copies per milliliter after starting combination antiretroviral therapy were eligible for inclusion. For each pair of VL <50 copies per milliliter, the annual change in CD4 count was calculated and compared between (1) HCV-seronegative vs. HCV-seropositive patients, (2) HCV genotypes 1-4 in HCV-RNA+ patients, and (3) viremic vs. aviremic (HCV-RNA < 615 IU/mL) in HCV-seropositive patients. Results were adjusted for known confounders. RESULTS: Four thousand two hundred eight patients were included, representing 39,474 pairs of HIV VL measurements with VL <50 copies per milliliter and 12,492 person-years of follow-up. The unadjusted annual change in CD4 count for HCV-seropositive and HCV-seronegative patients was 35.5 cells per milliliter (95% confidence interval 27.2 to 43.9) and 38.3 cells per milliliter (95%confidence interval 34.8 to 41.9), respectively. After adjustment, there was no difference in CD4 change when comparing, according to HCV serostatus (P = 0.17), between genotypes (P = 0.23) or when comparing HCV viremic vs. aviremic patients (P = 0.57). Adjusting additionally for HCV treatment and HCV-RNA VL did not change the findings. CONCLUSIONS: HCV serostatus did not influence the CD4 recovery in patients with HIV with maximum virologic suppression after starting combination antiretroviral therapy. Furthermore, no difference in CD4 gain was found when comparing distinct HCV genotypes in HCV-RNA+ patients or when comparing HCV viremic vs. aviremic HCV-seropositive patients.

HIV drug resistance tendencies in Latvia.

The treatment of HIV infection in Latvia by using highly active antiretroviral therapy (HAART) was started in 1996. The prevalence and tendencies of HIV drug resistance among treated and treatment-naive patients in Latvia in the years 2006-2007 were evaluated in this study. Data of HIV genotyping, performed in 132 HIV-1 infected during years 2006-2007 by TRUGENE HIV-1 genotyping assay (BayerHealthCare-diagnostics) are included in the study. Analysis of data showed that in the group of treatment-naive individuals majority carried wild type virus. Prevalence of resistance-associated mutations (RAMs) in the treatment-naive group according to IAS list was 28%. In most cases it was NRTI mutation A62V that is associated with multinucleoside resistance caused by Q151M, its effect in the absence of Q151M is not known. By many authors A62V is supposed to be a result of polymorphism in RT gene and is excluded from the list of resistance mutations. High prevalence of A62V is typical for HIV-1 subtype A. As majority of treatment-naive cases (89%) in this study were with HIV-1 subtypes A or AE, we excluded A62V mutation and estimated RAMs prevalence in group of treatment-naive HIV-infected individuals as 7%. Minor PI mutations were not included in analyses. In Europe published rates generally very between 5% and 15%. In the group of treatment-experienced HIV infected people 25/75 were with HIV-1 subtype B, the rest part--with non-B subtypes: A/AE (35/75), CRF-01AE (7/75), B/AE (4/75) and others. In treatment-experienced patients RAMs prevalence was estimated as 58.6%. Most frequently RAMs were found for nucleoside reverse transcriptase inhibitors (NRTI) (49.3%) followed by non-nucleoside reverse transcriptase inhibitors (NNRTI) (22.6%) and protease inhibitors (PI) (16%). In the group of NRTI mutations M184V (26/75; 34.6%), A62V (12/75; 16.0%) and T215Y (8/75; 10.6%), in NNRTI mutations K103N (10/75; 13.3%), G190S (6/75; 8.0%), in PI group mutations L90M (6/75; 8.0%) and M461/L (6/75; 8.0%) occurred most frequently. The following drug susceptibility was predicted according to the Trugen expert interpretations: in 33/75 (44%) patients no evidence of resistance, in 21/75 (28%) patients resistance to 1 drug class (NRTI--16/75, NNRTI--4/75, PI--1/75), in 17 patients (22.6%) resistance to 2 drug classes (NRTI+NNRTI--9/75, NRTI+PI--7/75, NNRTI+PI--1/75) and in 3/75 (4%) patients resistance to all 3 classes of drugs (NRTI+NNRTI+PI). We conclude, that prevalence of RAMs in treatment-naive HIV infected persons in Latvia is comparable with prevalence in Europe. The origin of predominated mutation A62V associated with NRTI at present is not clear. In more than half of treated HIV infected patients HIV resistance to at least one HAART class was predicted.

Fungal infection as a risk factor for HIV disease progression among patients with a CD4 count above 200/microl in the era of cART.

The identification of clinical risk factors for AIDS in patients with preserved immune function is of significant interest. We examined whether patients with fungal infection (FI) and CD4 cell count >or=200/microl were at higher risk of disease progression in the era of cART. 11,009 EuroSIDA patients were followed from their first CD4 cell count >or=200/microl after 1 January 1997 until progression to any non-azoles/amphotericin B susceptible (AAS) AIDS disease, last visit or death. Initiation of antimycotic therapy (AMT) was used as a marker of FI and was modelled as a time-updated covariate using Poisson regression. After adjustment for current CD4 cell count, HIV-RNA, starting cART and diagnosis of AAS-AIDS, AMT was significantly associated with an increased incidence of non-AAS-AIDS (IRR=1.55, 95% CI 1.17-2.06, p=0.0024). Despite low incidence of AIDS in the cART era, FI in patients with a CD4 cell count >or=200/microl is associated with a 55% higher risk of non-AAS-AIDS (95% confidence interval 1.17-2.06, p=0.0024). These data suggest that patients with FI are more immune compromized than would be expected from their CD4 cell count alone. FI can be used as a clinical marker for disease progression and indirect indicator for initiation/changing cART in settings where laboratory facilities are limited.

A Parkinsonian syndrome in methcathinone users and the role of manganese.

BACKGROUND: A distinctive extrapyramidal syndrome has been observed in intravenous methcathinone (ephedrone) users in Eastern Europe and Russia. METHODS: We studied 23 adults in Latvia who had extrapyramidal symptoms and who had injected methcathinone for a mean (+/-SD) of 6.7+/-5.1 years. The methcathinone was manufactured under home conditions by potassium permanganate oxidation of ephedrine or pseudoephedrine. All patients were positive for hepatitis C virus, and 20 were also positive for the human immunodeficiency virus (HIV). RESULTS: The patients reported that the onset of their first neurologic symptoms (gait disturbance in 20 and hypophonia in 3) occurred after a mean of 5.8+/-4.5 years of methcathinone use. At the time of neurologic evaluation, all 23 patients had gait disturbance and difficulty walking backward; 11 patients were falling daily, and 1 of these patients used a wheelchair. Twenty-one patients had hypophonic speech in addition to gait disturbance, and one of these patients was mute. No patient reported decline in cognitive function. T(1)-weighted magnetic resonance imaging (MRI) showed symmetric hyperintensity in the globus pallidus and in the substantia nigra and innominata in all 10 active methcathinone users. Among the 13 former users (2 to 6 years had passed since the last use), lesser degrees of change in the MRI signal were noted. Whole-blood manganese levels (normal level, <209 nmol per liter) averaged 831 nmol per liter (range, 201 to 2102) in the active methcathinone users and 346 nmol per liter (range, 114 to 727) in former users. The neurologic deficits did not resolve after patients discontinued methcathinone use. CONCLUSIONS: Our observation of a distinctive extrapyramidal syndrome, changes in the MRI signal in the basal ganglia, and elevated blood manganese levels in methcathinone users suggests that manganese in the methcathinone solution causes a persistent neurologic disorder.