icon-folder.gif   Conference Reports for NATAP  
  5th International Workshop on
HIV and Aging.
October 21-22, 2014
Back grey_arrow_rt.gif
PIs and Raltegravir Favored Over NNRTIs for Frail and Older People
  5th International Workshop on HIV and Aging. October 21-22, 2014. Baltimore
Mark Mascolini
Protease inhibitors (PIs) and the integrase inhibitor raltegravir got prescribed significantly more often for people in the oldest and frailest quartiles of an Italian HIV cohort [1]. Clinicians used nonnucleosides (NNRTIs) most often for the youngest and least frail patients.
Guidelines offer advice on antiretroviral options in patients with viral rebound, poor CD4 gains, or clinical developments. But researchers from the University of Modena and Reggio Emilia and colleagues from other institutions observed that clinicians may base antiretroviral choices on other criteria when they have to change regimens in people good virologic and CD4 responses. To address that question, they conducted this retrospective review, looking specifically for patterns of antiretroviral use and switching in relation to frailty, age, and gender.
Study participants received care at the Modena HIV Metabolic Clinic from 2005 through 2014. Everyone had taken antiretroviral combinations for more than 1 year, had an undetectable viral load, and had a CD4 count above 500. The investigators retrospectively calculated a frailty index as the proportion of deficits on a 45-item list, which excluded markers of HIV severity or immune deficiency. The index ranges from 0 (least frail) to 1.0 (most frail).
The Modena team considered regimens including (1) two NRTIs plus either a PI, an NNRTI, or raltegravir (the only licensed integrase inhibitor at the time), (2) megatherapy (more than 3 antiretrovirals (3) monotherapy, and (4) dual therapy (usually an NRTI-sparing regimen). They compared prevalence of antiretroviral regimens according to frailty index figured in 0.1 increments in multivariate models adjusted for age, gender, and nadir CD4 count (below 100, 101 to 350, 351 to 500, and above 500).
The study involved 1202 people with a visit to the Modena Metabolic Clinic during which clinicians considered antiretroviral regimens. Patient age averaged 50 years and 383 participants (32%) were women. Current median CD4 count stood at 721 (interquartile range 610 to 893), and frailty index averaged 0.30 (+/- 0.09). The most prevalent non-AIDS diseases were hypertension (42%), osteoporosis (24%), diabetes (13%), and chronic kidney disease (10%). Three quarters of study participants (75%) were taking triple therapy, 14% megatherapy, 7% dual therapy, and 4% monotherapy. Current regimens included a PI in 41%, an NNRTI in 37%, and raltegravir in 22%.
The researchers identified participants simultaneously in both the oldest quartile (older than 55) and the frailest quarter (frailty index above 0.37). Among current PI, NNRTI, or raltegravir regimens, NNRTI-based combinations were the least popular for people simultaneously in oldest and frailest quartiles, whereas they were the most popular for people simultaneously in the youngest and least frail quartiles. In contrast, current PI- and raltegravir-based regimens were highly favored in the oldest/frailest quartiles. PI regimens were also often prescribed for the youngest/least frail quartiles, though less often than NNRTI regimens (about 10% versus 16%).
Logistic regression analysis linked every 0.1 higher (worse) frailty index to about a 40% higher chance of current raltegravir use (RR 1.4, 95% confidence interval [CI] 1.14 to 1.7) or current PI use (RR 1.46, 95% CI 1.23 to 1.73). Older age and a nadir CD4 count below 200 favored current raltegravir regimens, but not independently. Multimorbidity favored PI and raltegravir regimens, but again not independently.
Every 10 years older age was associated with almost a 60% higher chance of current dual therapy (RR 1.58, 95% CI 1.13 to 2.21) and with a 40% higher chance of current NRTI-sparing therapy (RR 1.41, 95% CI 1.08 to 1.83). Frailty index, nadir CD4 count, and multimorbidity did not influence chances of current dual therapy, NRTI-sparing therapy, monotherapy, or megatherapy.
Cox regression analysis identified one independent predictor of a switch to a PI regimen: Every 10 years older age lowered chances of switching to a PI by 44% (HR 0.56, 95% CI 0.34 to 0.98). Male versus female gender lowered chances of switching to an integrase inhibitor by one third (HR 0.66, 95% CI 0.45 to 0.98).
The investigators stressed that the retrospective nature of this analysis precludes the possibility of identifying causal relationships being frailty index, age, or gender and antiretroviral use. They reminded colleagues that antiretrovirals are free in Italy, so cost does not factor into these analyses. Also, they did not include pill burden as a confounder in their multivariate analyses. Finally, they noted that the frailty index they used remains to be validated in other HIV cohorts.
Summarizing their findings, the Modena team observed that (1) women are more likely to switch to a raltegravir regimen, (2) older age is associated with unconventional regimens such as NRTI-sparing combinations, and (3) frailty favors prescription of a PI or raltegravir. The researchers proposed that their findings demonstrate "a clinical attitude towards antiretroviral selection that may incorporate global judgment about overall health status and vulnerability beyond traditional virological and immunological markers of HIV disease."
1. Guaraldi G, Brothers TD, Zona S, et al. Frailty and age are independently associated with patterns of HIV antiretroviral use in a clinical setting. 5th International Workshop on HIV and Aging. October 21-22, 2014. Baltimore. Abstract 10.