19th Annual CROI Conference: Focus on HIV and Comorbidities

The 19th Annual Conference on Retroviruses and Opportunistic Infections (CROI) just wrapped up in Seattle. Here are some of highlights:

Increased HIV Treatment Reduces Transmission in Populations

We know that treatment with antiretroviral therapy (ART) reduces viral transmission. Now there is evidence that this reduction may occur at the population level, too. A South African study used 2004 and 2011 data from longitudinal HIV and demographic surveillance of more than 10,000 adults 15 and older, compared to a control group of 16,588, to assess both treatment saturation and viral transmission.¹  The researchers found that every percentage point increase in ART coverage was associated with a 1.7% drop in the risk of HIV infection (P>0.001) of adults living in the same community.

Addressing Metabolic and Cardiovascular Disease in Persons with HIV

Compared to uninfected individuals, those infected with HIV have a much higher risk of comorbid diseases including cardiovascular disease, metabolic syndrome, and malignancies, likely due to increased inflammation that persists even with effective HIV treatment.²  Several studies presented at the CROI meeting address the issue of comorbidities from the perspective of prevention and treatment.

The first, from researchers at the University of Alabama at Birmingham, evaluated statin use and HIV deaths among 3,601 individuals who had not been taking a statin drug when they initiated antiretroviral therapy (ART). The researchers found a nonsignificant reduction of 18% in the time to first non-AIDS event and non-accidental death, but a significant 55% reduction in the development of cancer (adjusted hazard ratio, 0.45; confidence interval 0.21-0.97).³ 

Another study randomized 37 HIV-positive individuals on ART with undetectable HIV RNA levels to either an angiotensin converting enzyme (ACE) inhibitor/statin (lisinopril/pravastatin); placebo/pravastatin; lisinopril/placebo; or placebo. After 4 months, there was no significant difference in total cholesterol for patients on the statin, but there was a significant improvement in diastolic blood pressure in those receiving lisinopril (P=0.05), and improvements in the inflammatory biomarkers hsCRP and TNF-a (P=0.02 and 0.04, respectively) as well as the mean risk of all inflammatory markers (P=0.05).⁴ 

Finally, researchers from Massachusetts General Hospital in Boston conducted a 12-month, randomized, placebo-controlled trial to investigate the effects of lifestyle modification and metformin in reducing coronary artery calcification (CAC) in 50 HIV-positive patients with metabolic syndrome. The CAS is a strong predictor of cardiovascular disease. The metformin-treated patients demonstrated a significant reduction in CAC progression, calcified plaque volume, and other markers of cardiovascular risk compared to placebo. Those randomized to lifestyle modification showed significant improvements in high-density lipoprotein (HDL) levels and cardiorespiratory fitness, but no significant improvement in CAC.⁵Interactions Between New Hepatitis C Drugs and HIV Retrovirals

About a third of HIV patients are co-infected with hepatitis C (HCV). New HCV drugs approved in the past year (boceprevir and telaprevir) hold the promise of dramatically improving HCV treatment. However, there are concerns that the new HCV drugs may interfere with ART. Studies presented at the CROI meeting added to the concern and likely created some confusion.

One study in 39 healthy individuals with neither virus evaluated pharmacokinetic interactions between boceprevir and the commonly used protease inhibitors (PI) atazanavir (ATV), lopinavir (LPV), and darunavir (DRV) with low-dose ritonavir (r), typically administered as a pharmacokinetic booster with these drugs. Researchers from Merck, which manufactures and sells boceprevir, found that while co-administration was generally well tolerated, it reduced drug levels of all three PI drugs as well as ritonavir. While co-administration with ATV/r did not alter levels of boceprevir, co-administration with LPV/r and DRV/r did.⁶

However, another study of 24 healthy volunteers given boceprevir monotherapy for 10 days followed by the addition of raltegravir, or vice versa, found no effect on concentrations of either drug, with “no clinically meaningful effect” on raltegravir levels.⁷

Yet another study conducted in 98 HCV- and HIV-positive patients found that adding boceprevir to pegylated interferon plus ribavarin resulted in higher rates of undetectable HCV RNA in the treatment group compared to those receiving just pegylated interferon/ribavarin + placebo (63.9% vs 29.4%). Similar numbers of participants in both groups (2 and 3) experienced HIV RNA virologic failure.⁸  The authors did not report on pharmacokinetic outcomes.

So what’s a physician to do? A symposium on the topic didn’t make it any clearer, with a German researcher declaring that patients should not start boceprevir therapy with any HIV protease inhibitors, while a US researchers said it was “perfectly acceptable” to use boceprevir and telaprevir together with HIV drugs  as long as clinicians were aware of drug-drug interactions and closely monitored viral levels.
 

References:

1 Tanser F, et al. Effect of ART Coverage on Rate of New HIV Infections in a Hyper-endemic, Rural Population: South Africa . Abstract 136Lb2 HHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 2011.3 Overton E, et al. Effect of Statin Therapy on Reducing the Risk of Serious Non-AIDS-Defining Events and Non-Accidental Death: ACTG ALLRT Cohort. Abstract 124.4 Baker J, et al. ACEi or HMG-CoA Reductase Inhibitor (Statin) Treatment as Adjunct Therapy for Persons with HIV infection: A Pilot Study. Abstract 825.5 Fitch K, et al. Effects of Life-style Modification and Metformin on Coronary Calcium in HIV Patients with the Metabolic Syndrome