Juliette Pavie

Sensitivity of five rapid HIV tests on oral fluid or finger-stick whole blood: a real-time comparison in a healthcare setting.

Background Health authorities in several countries recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing, including the use of rapid tests. Several HIV rapid tests are now licensed in Europe but their sensitivity on total blood and/or oral fluid in routine healthcare settings is not known. Methods and Findings 200 adults with documented HIV-1 (n = 194) or HIV-2 infection (n = 6) were prospectively screened with five HIV rapid tests using either oral fluid (OF) or finger-stick whole blood (FSB). The OraQuick Advance rapid HIV1/2® was first applied to OF and then to FSB, while the other tests were applied to FSB, in the following order: Vikia HIV 1/2®, Determine HIV 1–2®, Determine® HIV-1/2 Ag/Ab Combo® and INSTI HIV-1/HIV-2®. Tests negative on FSB were repeated on paired serum samples. Twenty randomly selected HIV-seronegative subjects served as controls, and the results were read blindly. Most patients had HIV-1 subtype B infection (63.3%) and most were on antiretroviral therapy (68.5%). Sensitivity was 86.5%, 94.5%, 98.5%, 94.9%, 95.8% and 99% respectively, with OraQuick OF, OraQuick FSB, Vikia, Determine, Determine Ag/Ab Combo and INSTI (p<0.0001). OraQuick was less sensitive on OF than on FSB (p = 0.008). Among the six patients with three or more negative tests, two had recent HIV infection and four patients on antiretroviral therapy had undetectable plasma viral load. When patients positive in all the tests were compared with patients who had at least one negative test, only a plasma HIV RNA level <200 cp/ml was significantly associated with a false-negative result (p = 0.009). When the 33 rapid tests negative on FSB were repeated on serum, all but six (5 negative with OraQuick, 1 with INSTI) were positive. The sensitivity of OraQuick, Determine and Determine Ag/Ab Combo was significantly better on serum than on FSB (97.5%, p = 0.04; 100%, p = 0.004; and 100%, p = 0.02, respectively). Conclusion When evaluated in a healthcare setting, rapid HIV tests were less sensitive on oral fluid than on finger-stick whole blood and less sensitive on finger-stick whole blood than on serum.

Breakthrough Disseminated Aspergillus ustus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients Receiving Voriconazole or Caspofungin Prophylaxis

ABSTRACT Aspergillus ustus is an uncommon clinical species which is poorly susceptible to antifungals. We report two cases of A. ustus infections that occurred in allogeneic stem cell transplant recipients while they were receiving either voriconazole or caspofungin. Prolonged use of these new antifungal agents may increase the risk of the emergence of resistant organisms.

Clinically Relevant Genotype Interpretation of Resistance to Didanosine

ABSTRACT We analyzed the didanosine (ddI) arm of the randomized, placebo-controlled Jaguar trial in order to define a genotypic score for ddI associated with virologic response. In this arm, 111 patients experiencing virologic failure received ddI in addition to their current combination therapy for 4 weeks. The impact of mutations in the reverse transcriptase gene on the virologic response to ddI was studied in univariate analysis. Genotypic score was constructed using step-by-step analyses first including only mutations associated to poorer virologic response (scored as +1), while secondarily, mutations associated to a better response (scored as −1) were also eligible. Eight mutations were associated with a reduced response to ddI, M41L, D67N, T69D, L74V, V118I, L210W, T215Y/F, and K219Q/E, and two mutations were associated with a better response, K70R and M184V/I. The best prediction of the virologic response to ddI was obtained with a composite score comprising mutations added and subtracted (set II, M41L + T69D + L74V+ T215Y/F + K219Q/E − K70R − M184V/I; P = 4.5 × 10−9) and by comparing that to only mutations added (set I, M41L + T69D + L74V + L210W + T215Y/F + K219Q/E; P = 1.2 × 10−7). Patients had a human immunodeficiency virus RNA reduction of 1.24, 0.84, 0.61, 0.40, and 0.07 log10 copies/ml when they were ranked as having a genotypic score II of −2, −1, or 0 or 1 and 2 mutations or more, respectively. In conclusion, we developed and validated a genotypic score, taking into account mutations negatively and positively impacting the virologic response to ddI.

Didanosine in HIV-1–Infected Patients Experiencing Failure of Antiretroviral Therapy: A Randomized Placebo-Controlled Trial

BACKGROUND The antiviral efficacy of didanosine in patients experiencing virological failure is not well known. METHODS A total of 168 patients (139 men and 29 women) receiving stable antiretroviral therapy with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 1000-100,000 copies/mL were randomly assigned to have didanosine (n=111) or placebo (n=57) added to their currently failing regimen for 4 weeks. The primary efficacy end point was the change in HIV-1 RNA level from baseline to week 4. RESULTS At baseline, the median HIV-1 RNA level was 3.8 log(10) copies/mL, the median CD4 cell count was 378 cells/mm(3), and the median number of nucleoside reverse-transcriptase inhibitor-associated mutations (NAMs) was 4. At week 4, a significant decrease in the median HIV-1 RNA level was observed in the didanosine group, compared with that in the placebo group (-0.56 vs. +0.07 log(10) copies/mL, respectively) (P<.0001). A total of 33 patients (31%) in the didanosine group, compared with 3 (6%) in the placebo group, had HIV-1 RNA levels <400 copies/mL (P<.001). Significant antiviral activity of didanosine was observed in patients with up to 5 NAMs at baseline. Diarrhea occurred in 5 patients (5%) in the didanosine group and 2 patients (4%) in the placebo group. CONCLUSIONS In HIV-1-infected patients experiencing failure of antiretroviral therapy, didanosine retains short-term antiviral activity.

Comparative RNA Quantification of HIV-1 Group M and Non-M With the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 v2.0 and Abbott Real-Time HIV-1 PCR Assays

Background: A new version of the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 assay (CA/CTM v2.0) has been introduced to overcome the underquantification observed with the first version. Methods: We compared the Roche Cobas CA/CTM v2.0 and Abbott RealTime HIV-1 assays for HIV-1 group M and non-M viral load measurement. Results: We found a good correlation (r = 0.96) between the 2 techniques for the 260 HIV-1 group M plasma samples tested. The Roche Cobas assay gave significantly higher values than the Abbott assay, and 51 samples (20%) yielded differences greater than 0.5 log10 copies per milliliter. Conversely, 2 samples were more than 0.5 log10 copies per milliliter higher with the Abbott assay than with the Roche Cobas assay. Among the 84 samples with undetectable viral load in the Abbott assay (detection limit 40 copies/mL), 17 (20%) were detectable with the CA/CTM v2.0 assay (detection limit 20 copies/mL), with values ranging from 41 to 897 copies per milliliter. Extrapolation of the Abbott curves led to 10/17 (59%) of these samples being quantifiable. HIV-1 groups O and P were similarly quantified by the two techniques. Conclusion: The results of the Roche Cobas CA/CTM v2.0 and Abbott RealTime HIV-1 assays correlate well. The new version of the CA/CTM assay shows improved sensitivity. Nevertheless, the 2 assays differ by more than 0.5 log10 copies per milliliter for some samples.

Restoration of Toxoplasma gondii-specific immune responses in patients with AIDS starting HAART.

Objective:To study the kinetics and identify factors associated with Toxoplasma-specific immune responses in patients with AIDS starting antiretroviral therapy. Methods:A prospective study of 38 HIV-infected patients seropositive for Toxoplasma who started antiretroviral therapy with CD4 T cells less than 200 cells/μl. T-cell and B-cell phenotypes, anti-Toxoplasma antibodies titers, Th-1 and Th-2 cytokine production and lymphocyte proliferative responses (LPRs) to Toxoplasma were assessed over 12 months. Results:Median CD4 cell count increased from 122 cells/μl at baseline to 260 cells/μl at 12 months, and the incidence of a positive LPR from 18.4 to 70.5%. A Toxoplasma IgG titer more than 150 IU/ml was the only baseline variable associated with a positive LPR (hazard ratio: 4.6, P = 0.003). Among time-dependent covariates, the number of effector memory (CD45RA−CCR7−) CD4 T cells was associated with a positive LPR (P < 0.02) and the number of terminally differentiated (CD45RA+CCR7−) CD8 T cells was associated with in-vitro production of γ-IFN (P < 0.008). Conclusion:Among patients with low CD4 cell counts, high anti-Toxoplasma IgG titers were associated with LPR to Toxoplasma antigen. After starting antiretroviral therapy, the number of effector memory CD4 T cells and terminally differentiated CD8 T cells were associated with the restoration of Toxoplasma LPR and γ-IFN production, respectively.

Pattern and impact of emerging resistance mutations in treatment experienced patients failing darunavir-containing regimen

Background:Ritonavir-boosted darunavir (DRV/r) has proven potent efficacy when used in heavily pretreated patients, harboring protease inhibitor-associated resistance mutations. Limited data are available on resistance pattern emerging in patients failing DRV/r and on subsequent remaining protease inhibitor options. Methods:Analysis of baseline and failure resistance genotypes were performed in patients experiencing virologic failure (>200 copies/ml) after at least 3 months on a DRV/r (600/100 mg twice daily)-containing regimen. Results:Twenty-five highly protease inhibitor-experienced patients were included. Baseline median human immunodeficiency virus type 1 RNA was 5 log10 copies/ml and number of total-protease inhibitor, major-protease inhibitor and DRV-associated-resistance mutations was 13, 4 and 3, respectively. Median viral replication duration on DRV/r selective pressure was 34 weeks. Emergence of DRV-associated-resistance mutations was observed in 72% (18/25) of patients, at codons L89I/M/V (32%), V32I (28%), V11I (20%), I47V/A (20%), I54L/M (20%), L33F/I (16%) and I50V (16%). A high risk of DRV resistance was observed in patients with 2 and 3 baseline DRV-associated-resistance mutations and in patients with more than 24 weeks of ongoing viral replication. According to 2007 ANRS algorithm, isolates classified as susceptible to ritonavir-boosted tipranavir decreased from baseline to failure from 76 to 60% and susceptible to DRV/r from 32 to 12%. Conclusion:Emerging mutations observed after DRV/r failure were those already described to impact the DRV efficacy. Our study provided recommendations to firstly, reconsider lowering the cutoff number of DRV mutations to two; secondly, avoid keeping patients on a DRV-failing regimen for more than 24 weeks and thirdly, to examine the efficacy of using tipranavir after DRV failure.

Impact on Health-Related Quality of Life of a Switch From Enfuvirtide to Raltegravir Among Multidrug-Resistant HIV-1–Infected Patients: A Randomized Open-Label Trial (EASIER-ANRS 138)

Abstract Background: Among multidrug-resistant HIV-1–infected patients, enfuvirtide has demonstrated sustained efficacy, but long-term use is inconvenient due to twice-daily subcutaneous injections which often induce injection-site reactions. We investigated whether a switch from enfuvirtide to raltegravir, an orally available HIV-integrase inhibitor, may improve health-related quality of life (HRQoL). Methods: 170 multidrug-resistant HIV–1–infected patients who were receiving enfuvirtide-based regimens were randomised to the maintenance of enfuvirtide or the switch to raltegravir at day 0. At week 24, all patients received raltegravir up to week 48. HRQoL was assessed at baseline and weeks 24 and 48 using a self-report MOS-HIV questionnaire. HRQoL scores were compared between arms using analysis of covariance (ANCOVA) models. Results: At week 24, least-squares means changes from baseline for the maintenance and the substitution arms were –5.3 and +5.8 (P = .001) for the pain score, –4.7 and +4.8 (P = .02) for the social functioning score, and –1.3 and +2.0 (P = .003) for the physical summary score, respectively. Conclusion: Among multidrug-resistant HIV-1–infected patients, a switch from enfuvirtide to raltegravir resulted in statistically significant improvements in multiple HRQoL dimensions over 24 weeks in comparison to the maintenance under enfuvirtide.

Later cART initiation in migrant men from sub-Saharan Africa without advanced HIV disease in France.

Objective To compare the time from entry into care for HIV infection until combination antiretroviral therapy (cART) initiation between migrants and non migrants in France, excluding late access to care. Methods Antiretroviral-naïve HIV-1-infected individuals newly enrolled in the FHDH cohort between 2002–2010, with CD4 cell counts >200/μL and no previous or current AIDS events were included. In three baseline CD4 cell count strata (200–349, 350-499, ≥500/μL), we examined the crude time until cART initiation within three years after enrolment according to geographic origin, and multivariable hazard ratios according to geographic origin, gender and HIV-transmission group, with adjustment for baseline age, enrolment period, region of care, plasma viral load, and HBV/HBC coinfection. Results Among 13338 individuals, 9605 (72.1%) were French natives (FRA), 2873 (21.4%) were migrants from sub-Saharan Africa/non-French West Indies (SSA/NFW), and 860 (6.5%) were migrants from other countries. Kaplan-Meier probabilities of cART initiation were significantly lower in SSA/NFW than in FRA individuals throughout the study period, regardless of the baseline CD4 stratum. After adjustment, the likelihood of cART initiation was respectively 15% (95%CI, 1–28) and 20% (95%CI, 2–38) lower in SSA/NFW men than in FRA men who had sex with men (MSM) in the 350-499 and ≥500 CD4 strata, while no difference was observed between other migrant groups and FRA MSM. Conclusion SSA/NFW migrant men living in France with CD4 >350/μL at entry into care are more likely to begin cART later than FRA MSM, despite free access to treatment. Administrative delays in obtaining healthcare coverage do not appear to be responsible.

Severe Acute Renal Failure in an HIV-Infected Patient After Only 2 Weeks of Tenofovir-Based Antiretroviral Therapy

We report a 46-year-old man who has sex with men (MSM) patient, of Scottish descent, who had no history of arterial hypertension, diabetes, or illicit drug use, was hepatitis C virus (HCV) negative but underwent right nephrectomy for urothelial tumor in 2006. Before starting antiretroviral therapy, he had a CD4 cell count of 316/mm(3) and plasma HIV RNA level was 1,020,537 copies per milliliter. He developed acute renal failure only 2 weeks after introduction of tenofovir-based antiretroviral therapy and then required 3 months of hemodialysis. After the end of hemodialysis, antiviral therapy was resumed with abacavir (300 mg×2/day), lamivudine (300 mg every day), and lopinavir/ritonavir (400/100 mg twice daily). Renal biopsy revealed severe and diffuse toxic acute tubular necrosis Two years after tenofovir discontinuation, the patients renal function remained subnormal. Although severe renal toxicity due to tenofovir is rare, patients receiving tenofovir must be monitored closely for renal dysfunction especially during the first weeks of tenofovir therapy.