Life Expectancy Rising in HIV Group Over 50, But Still Lags General Population

Estimated median survival in the HIV group rose from 11.8 years in 1996-1999 to 17.8 years in 2000-2005 and to 22.5 years in 2006-2014. Median survival in general population controls was 30.2 years across all three periods. Mortality rate ratio comparing HIV-positive people with controls was highest among 50- to 55-year-olds (3.8) and declined in each older age group. But in the oldest age group, 75- to 80-year-olds, people with HIV still had a significantly higher death rate than population controls (mortality rate ratio 1.6, 95% confidence interval [CI] 1.0 to 2.6). Mortality did not differ substantially between HIV-positive people diagnosed before or after age 50.
The “well-treated” subset included 517 people with HIV and 3192 age- and gender-matched general-population controls. Estimated median survival from age 50 was 25.6 years in the HIV group (to age 75.6) versus 34.2 years in controls (to age 84.2). Those numbers meant people with HIV but without AIDS or comorbidities had a 70% higher death rate than general-population controls without comorbidities (mortality rate ratio 1.7, 95% CI 1.2 to 2.3).
The researchers concluded that “survival after age 50 has improved markedly in the HIV-population within the [combination ART] era, but is still substantially lower than in the background population,” even in “well-treated” HIV-positive people without AIDS or comorbidities.

New HIV Drug Has Potential for Weekly or Once-Yearly Dosing

One of the surprises at CROI 2016 was the first virological data from a new highly potent NRTI that in a slow-release formulation has the potential for annual dosing and that is undergoing research as both treatment and PrEP.

In an oral late-breaker, Jay Grobler from Merck presented results from a dose-ranging study in macaques to develop a model for phase 1 studies with MK-8591 (EFdA).1

Baseline SHIV viral load ranged from 6 to 8 log copies/mL and following single doses that ranged from 3.9 to 18.2 mg/kg viral load dropped by approximately 1.5 logs and was sustained for seven days.

PK data from a phase 1 multiple-dose study in HIV negative adults (using 10 mg, 30 mg and 100 mg) once-weekly for three weeks showed that with the 10 mg dose target intracellular target drug concentrations were exceeded for more than seven days.

A slightly cheeky slide was shown from the phase 1b study showing that EFdA produced more rapid viral suppressions compared to historical data for TDF and TAF.

Early data on a solid-state slow release parenteral injection formulation that has an option for removability, showed sustained release for more than 180 days in rat studies, with the potential for cover to be extended to a year.

Switching HIV+ Patients From Stribld to Genvoya Improved Proteinuria but Not eGFR

CROI 2016 Conference
Abstract Number: 

Safety of Tenofovir Alafenamide in Renal Impairment

Anton Pozniak2, Jose R Arribas3, Samir K. Gupta4, Frank A. Post5, Anchalee Avihingsanon6, Gordon Crofoot7, Kenneth A. Lichtenstein8, Moti Ramgopal9, Ploenchan Chetchotisakd10, Marshall W. Fordyce1
1 Clinical Research, Gilead Sciences Inc, Foster City, CA, United States. 2 Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom. 3 Hospital Universitario La Paz, Madrid, Spain. 4 Indiana University School of Medicine, Indianapolis, IN, United States. 5 King’s College Hospital NHS Foundation Trust, London, United Kingdom. 6 HIV-NAT, Thai Red Cross AIDS Research Center and Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 7 Crofoot Research, Houston, TX, United States. 8 National Jewish Health, Denver, CO, United States. 9 Midway Research Center, Ft. Pierce, FL, United States. 10 Khon Kaen University, Khon Kaen, Thailand.
Abstract Body: 
Background: Tenofovir (TFV) is renally eliminated, and the prodrug, tenofovir disoproxil fumarate (TDF), has been associated with renal toxicity and reduced bone mineral density (BMD), and must be dose adjusted in patients with estimated glomerular filtration rate (eGFR) < 50mL/min. Tenofovir alafenamide (TAF) is a novel prodrug of TFV that is not renally eliminated and at clinical doses results in 90% lower plasma TFV levels as compared to TDF. The safety and efficacy of a once-daily single tablet regimen of elvitegravir, cobicistat, emtricitabine, and TAF (E/C/F/TAF) was assessed in HIV-1 infected patients with mild to moderate renal impairment.
Methods: Virologically suppressed adults with stable eGFRCG (Cockroft”‘Gault) of 30 to 69 mL/min had their treatment switched from both TDF- and non-TDF-containing regimens to open-label E/C/F/TAF. Week 24 efficacy and safety data are described, including tests of renal function and BMD. Actual GFR (aGFR) was assessed with iohexol clearance in a subset of subjects.
Results: Of 242 subjects enrolled and dosed, mean age was 58 years (range: 24 – 82), 18% Black, 39% hypertension, and 14% diabetes. 65% were taking TDF-containing regimens prior to switch. At baseline, median eGFRC-G was 55.6 mL/min (33% eGFRC-G 30-49 mL/min). 95% of subjects maintained HIV-1 VL C-G

 was -0.4 (-4.7, 4.5) mL/min, eGFR-cystatin C 3.8 (-4.8, 11.2) mL/min/1.73m2, and aGFR (n=32, 68.8% TDF at baseline) was 0.1 (-4.3, 4.4) mL/min, indicating that GFR was not affected by E/C/F/TAF. Two subjects (0.8%) discontinued study drug for decreased GFR by eGFRC-G and eGFR-cystatin C, neither with evidence of renal tubulopathy. The prevalence of clinically significant proteinuria (UPCR > 200 mg/g) and albuminuria (UACR ≥ 30 mg/g) decreased from 42% to 21% and 49% to 27%, respectively. Significant decreases in urine retinol binding protein to creatinine ratio, beta”‘2”‘microglobulin to creatinine ratio, and fractional excretion of uric acid were observed (p

Conclusions: These 24 week data support the virologic efficacy and renal and bone safety of once daily single-tablet E/C/F/TAF for use in HIV+ patients with mild and moderate renal impairment (eGFR 30 to 69 mL/min). Switch to E/C/F/TAF was associated with no change in aGFR and with reductions in proteinuria.
Session Number: 
Session Title: 
Renal Dysfunction: ART and Biomarkers
Presenting Author: 
Pozniak, Anton
Presenter Institution: 
Chelsea and Westminster Hospital NHS Foundation Trust

HIV Mutates Around Promising Gene Editing Technology (CRISPR-CAS 9)

HIV can defeat efforts to cripple it with CRISPR gene-editing technology, researchers say. And the very act of editing — involving snipping at the virus’s genome — may introduce mutations that help it to resist attack.
At least half a dozen papers over the past three years have explored using the popular CRISPR–Cas9 gene editing technique to combat HIV, but the latest finding, described in a study published on 7 April in Cell Reports1, adds to questions about the feasibility of the approach. However, the researchers involved say that the discovery is a minor setback that does not preclude the idea altogether.