Pierre Palmer

Simplification Therapy with Once-Daily Emtricitabine, Didanosine, and Efavirenz in HIV-1–Infected Adults with Viral Suppression Receiving a Protease Inhibitor–Based Regimen: A Randomized Trial

BACKGROUND We assessed a once-daily combination to simplify therapy in patients infected with human immunodeficiency virus type 1 (HIV-1). METHODS A total of 355 adults with plasma HIV-1 RNA levels <400 copies/mL were randomly assigned to either switch to once-daily emtricitabine, didanosine, and efavirenz (n=178) or maintain their protease inhibitor (PI)-based regimens (n=177). The primary end point was sustained suppression of plasma HIV-1 RNA levels to <400 copies/mL. RESULTS At week 48, the proportion of patients meeting the end point was 87.6% in the PI group and 90.5% in the once-daily group, with a treatment difference of -2.9% (upper bound of the 1-tailed 95% confidence interval, 2.6%). The proportion of patients with HIV-1 RNA levels <50 copies/mL was higher in the once-daily group (87%) than in the PI group (79%) (P<.05). Resistance mutations to efavirenz and emtricitabine were detected in all patients in the once-daily group who experienced virologic failure while receiving study medication. The proportion of patients discontinuing study medication because of adverse events was similar between the once-daily group (9%) and the PI group (10%) (P=.8). CONCLUSIONS Substituting a convenient once-daily combination of emtricitabine, didanosine, and efavirenz for a PI-based regimen was well tolerated and associated with sustained virologic suppression.

Survival trends in critically ill HIV-infected patients in the highly active antiretroviral therapy era

IntroductionThe widespread use of highly active antiretroviral therapy (ART) has reduced HIV-related life-threatening infectious complications. Our objective was to assess whether highly active ART was associated with improved survival in critically ill HIV-infected patients.MethodsA retrospective study from 1996 to 2005 was performed in a medical intensive care unit (ICU) in a university hospital specialized in the management of immunocompromised patients. A total of 284 critically ill HIV-infected patients were included. Differences were sought across four time periods. Risk factors for death were identified by multivariable logistic regression.ResultsAmong the 233 (82%) patients with known HIV infection before ICU admission, 64% were on highly active ART. Annual admissions increased over time, with no differences in reasons for admission: proportions of patients with newly diagnosed HIV, previous opportunistic infection, CD4 counts, viral load, or acute disease severity. ICU and 90-day mortality rates decreased steadily: 25% and 37.5% in 1996 to 1997, 17.1% and 17.1% in 1998 to 2000, 13.2% and 13.2% in 2001 to 2003, and 8.6% in 2004 to 2005. Five factors were independently associated with increased ICU mortality: delayed ICU admission (odds ratio (OR), 3.04; 95% confidence interval (CI), 1.29 to 7.17), acute renal failure (OR, 4.21; 95% CI, 1.63 to 10.92), hepatic cirrhosis (OR, 3.78; 95% CI, 1.21 to 11.84), ICU admission for coma (OR, 2.73; 95% CI, 1.16 to 6.46), and severe sepsis (OR, 3.67; 95% CI, 1.53 to 8.80). Admission to the ICU in the most recent period was independently associated with increased survival: admission from 2001 to 2003 (OR, 0.28; 95% CI, 0.08 to 0.99), and between 2004 and 2005 (OR, 0.13; 95% CI, 0.03 to 0.53).ConclusionsICU survival increased significantly in the highly active ART era, although disease severity remained unchanged. Co-morbidities and organ dysfunctions, but not HIV-related variables, were associated with death. Earlier ICU admission from the hospital ward might improve survival.

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.

Clinical and Resistance Consequences of Misquantification of Plasma and Cerebrospinal Fluid Human Immunodeficiency Virus Type 1 (HIV-1) RNA in Samples from an HIV-1 Subtype G-Infected Patient

ABSTRACT Human immunodeficiency virus (HIV) load is the main marker used to monitor antiviral treatment efficacy and resistance. We report a case of underquantification of HIV type 1 (HIV-1) RNA in plasma and cerebrospinal fluid from an HIV-1 subtype G-infected woman, leading to delayed diagnosis of HIV encephalitis and to the emergence of drug resistance.

Four year follow-up of simplification therapy with once-daily emtricitabine, didanosine and efavirenz in HIV-infected patients (ALIZE ANRS 099 trial)

BACKGROUND once-daily combinations of efavirenz and two nucleoside analogues are recommended for the treatment of HIV infection. Long-term efficacy and safety data are scarce for the combination of efavirenz, emtricitabine and didanosine. METHODS the ALIZE ANRS 099 trial enrolled 355 adults with plasma HIV RNA levels of <400 copies/mL under a protease inhibitor-based regimen, who were randomized to remain on this regimen or to switch to a once-daily regimen of emtricitabine, didanosine and efavirenz for 48 weeks. An extended 4 year follow-up was available for the 178 patients who switched to the efavirenz-containing regimen, and assessed plasma HIV RNA levels, CD4 cell counts, safety and tolerability. RESULTS after a median follow-up of 42 months, 121 patients (68%) remained on an efavirenz-based regimen, and 62% and 57% had plasma HIV RNA levels of <400 and <50 copies/mL, respectively, in an intent-to-continue analysis with missing data and treatment discontinuation considered as failure. There was a significant increase in CD4 cell count of 41 cells/mm(3). Drug-related adverse events were the main reason for treatment discontinuation in 26 patients (15%), and 15 were reported during the first year of therapy (58%). There was no emergence of clinically defined lipodystrophy, and lipid and glucose profiles were favourable with a significant increase from baseline of high-density lipoprotein cholesterol levels (median increase 12 mg/dL, P < 10(-4)). CONCLUSIONS a once-daily regimen of emtricitabine, didanosine and efavirenz provided a durable antiretroviral response and was well tolerated through 4 years of therapy.

One or two enzyme-linked immunosorbent assay tests on the first serum sample for initial diagnosis of HIV-1 infection?

In France, the first sample for the initial diagnosis of HIV-1 infection must be tested with two antibody assays: one being an enzyme-linked immunosorbent assay. If one is positive, confirmation tests are performed. We evaluated the performance of initial diagnostic strategies based on the use of one versus two enzyme-linked immunosorbent assay tests, either an antigen-antibody test or a simple antibody assay. We found that a single antigen-antibody test was more efficient than a combination of the two tests.

Case report: cure of chronic infection with hepatitis C virus after 6 weeks of peg-interferon and ribavirin in a patient co-infected with HIV.

The recommended treatment duration of chronic hepatitis C virus (HCV) in patients infected with human immunodeficiency virus (HIV) is 48 weeks. This report describes a patient co‐infected with HCV genotype 2 and HIV who discontinued HCV therapy after 6 weeks because of adverse events and had a sustained virologic response. J. Med. Virol. 82:1150–1151, 2010.