Antiretroviral Therapy for HIV Patients

SOURCE: Rodger AJ, Cambiano V, Bruun T, et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner Is using suppressive antiretroviral therapy. JAMA 2016;316:171-181.

Prevention of seroconversion in HIV serodiscordant couples (in which one partner is HIV positive and the other is not) is reduced by using barrier methods, especially when the HIV-positive partner is receiving antiretroviral therapy (ART). ART provides sustained reductions in HIV viral load and reduced infectivity, but would it be safe for serodiscordant couples to omit barrier methods entirely?

Rodger et al performed a prospective observational study (n = 888) of serodiscordant sexually active heterosexuals, men who have sex with men (MSM), and gay couples. The HIV-positive partners all were receiving ART, and > 80% presented with undetectable levels of HIV virus (some subjects on ART did not report viral load status, but are presumed to be similarly undetectable). Couples agreed to abstain from barriers during intravaginal or intra-anal intromission.

During 1.3 years (mean) of follow-up, there were no confirmed HIV conversions; any new HIV conversions were found to be from HIV strains not harbored by the HIV-positive partner and must have occurred from another external HIV-positive source.

Since intra-anal transmission is more common than intravaginal transmission, it is particularly welcome that the rate of conversion was zero among all participants, including the 340 MSM.

Ticagrelor vs. Aspirin in Post-TIA and Stroke Patients

SOURCE: Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med 2016;375:35-43.

The first 90 days after a transient ischemic attack (TIA) or ischemic stroke is a high-risk period for recurrence of cardiovascular thrombotic events. Even with aspirin treatment, recurrences occur in as many as 10-15% of patients. Ticagrelor is an inhibitor of the P2Y12 receptor on platelets, similar in mechanism to clopidogrel. Ticagrelor is indicated for reduction of thrombotic events in persons with acute coronary syndromes or ST-elevation myocardial infarction. Might a different mechanism of action than aspirin treatment, as provided by ticagrelor, reduce thrombotic events in patients who experience a TIA?

The SOCRATES trial enrolled patients (n = 13,199) who had suffered an ischemic stroke or TIA within 24 hours of the event. Study subjects were randomized to ticagrelor (180 mg loading dose, then 90 mg twice per day) or aspirin (300 mg loading, then 100 mg once per day) for 90 days. The primary outcome was a composite of stroke, myocardial infarction, or death.

Although results trended favorably in the ticagrelor treatment arm (hazard ratio = 0.89), they were not statistically significant. Since the treatment costs of aspirin are substantially less than ticagrelor, and the adverse bleeding effect profile is similar, aspirin should remain the drug of choice, except for patients who are aspirin intolerant.

Many Treatment Choices for Type 2 Diabetes

SOURCE: Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: A meta-analysis. JAMA 2016;316:313-324.

The real goals of diabetes treatment are reduction in microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular (myocardial infarction and stroke) endpoints. With that in mind, it should be sobering to review current FDA-approved labeling for antidiabetic meds: “There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with [insert drug name] or any other anti-diabetic drug.”

A recent large meta-analysis (301 clinical trials) addressed cardiovascular mortality as well as all-cause mortality for the most commonly used antidiabetic drugs (metformin, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, insulin, DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 receptor agonists) seeking to discern any differences in cardiovascular events or mortality, as well as safety.

Despite an impressive amount of data, no particular class of agents — as monotherapy or in combination — provided distinct advantages for risk reduction of cardiovascular events or mortality.

Recent cardiovascular safety trials featuring two agents (empagliflozin and liraglutide) challenge the concept that diabetes treatment is ineffectual for cardiovascular risk reduction, but if clinicians believe in “class effects” of medications, it appears dubious that any clear winners will emerge any time soon in the quest for cardiovascular risk reduction.