The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years

To characterize the safety profile of tenofovir disoproxil fumarate (DF) for the treatment of HIV infection in adults over the first 4 years of use. A tenofovir DF expanded access program (EAP) was initiated in 2001; safety data were examined from this program and from the manufacturer's database, which contained reports of all postmarketing adverse drug reactions received up to 30 April 2005. Specific analyses were performed to characterize the renal safety of tenofovir DF. The EAP enrolled 10 343 patients; serious adverse events (SAEs) were reported in 631 (6%). A renal SAE of any type was observed in 0.5% of patients, and graded elevations in serum creatinine occurred in 2.2% of the patients evaluated. In a multivariate analysis, baseline risk factors for the development of increased serum creatinine on-study were elevated serum creatinine, concomitant nephrotoxic medications, low body weight, advanced age, and lower CD4 cell count. For postmarketing safety data (455 392 person-years of exposure to tenofovir DF) the most commonly reported serious adverse drug reactions were renal events, with a distribution by type similar to that observed in the EAP. Bone abnormalities were infrequently reported in either the EAP or the postmarketing safety databases. No new unexpected toxicities were identified in postmarketing safety surveillance. The data demonstrate a favorable safety profile for tenofovir DF in the treatment of adults with HIV infection. Risk factors for development of nephrotoxicity can be identified and may be useful in managing those patients at greatest ris

The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years

To characterize the safety profile of tenofovir disoproxil fumarate (DF) for the treatment of HIV infection in adults over the first 4 years of use. A tenofovir DF expanded access program (EAP) was initiated in 2001; safety data were examined from this program and from the manufacturer's database, which contained reports of all postmarketing adverse drug reactions received up to 30 April 2005. Specific analyses were performed to characterize the renal safety of tenofovir DF. The EAP enrolled 10 343 patients; serious adverse events (SAEs) were reported in 631 (6%). A renal SAE of any type was observed in 0.5% of patients, and graded elevations in serum creatinine occurred in 2.2% of the patients evaluated. In a multivariate analysis, baseline risk factors for the development of increased serum creatinine on-study were elevated serum creatinine, concomitant nephrotoxic medications, low body weight, advanced age, and lower CD4 cell count. For postmarketing safety data (455 392 person-years of exposure to tenofovir DF) the most commonly reported serious adverse drug reactions were renal events, with a distribution by type similar to that observed in the EAP. Bone abnormalities were infrequently reported in either the EAP or the postmarketing safety databases. No new unexpected toxicities were identified in postmarketing safety surveillance. The data demonstrate a favorable safety profile for tenofovir DF in the treatment of adults with HIV infection. Risk factors for development of nephrotoxicity can be identified and may be useful in managing those patients at greatest ris

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

BACKGROUND The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence