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  ID Week
Oct 8-12 2014
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Gender, Depression, Heart and Liver Disease Affect First-Line ART Choice in US
  IDWeek 2014, October 8-12, 2014, Philadelphia
Mark Mascolini
Women and people with depression or liver disease were less likely to start antiretroviral therapy (ART) with a nonnucleoside (NNRTI) in a 1215-person 8-clinic US analysis [1]. Women and people with depression were more likely to start a protease inhibitor (PI), while people with depression or heart disease were more likely to start the integrase inhibitor raltegravir.
As antiretroviral regimens become stronger, easier to tolerate, and more convenient, CNICS researchers who conducted this study noted, the number of feasible first-line combinations has climbed. Although scores of trials compare many standard first-line regimens, scant research explores which regimens people in care begin and which factors might influence choice of a first-line prescription. To address those questions, the CNICS team conducted this study.
CNICS--the CFAR Network of Integrated Clinical Systems--consists of 8 HIV clinics at academic centers across the United States. This analysis included all patients who started three or more antiretrovirals between July 2009 and December 2012. The researchers divided them into those who started an NNRTI, a ritonavir-boosted PI, or raltegravir. They used three separate multivariable logistic regression models to explore factors possibly associated with starting treatment with an NNRTI, a PI, or raltegravir. The reference group for each model was all initial regimens other than the one being analyzed.
The study included 1215 people--813 men who have sex with men (MSM) (67%), 191 heterosexual men (16%), and 211 women (17%). NNRTI combinations were the most popular first-line choice, begun by 650 people (53%), followed by PI regimens started by 455 people (37%) and raltegravir started by 110 (9%).
Proportions of whites, blacks, and Hispanics were 56%, 34%, and 19%. The cohort included 170 injection drug users (14%). Most people had public insurance (57%), while some had private insurance (29%) and some had no insurance (14%). One quarter of study participants had a pretreatment viral load above 100,000 copies, 24% had a pretreatment CD4 count below 200, and 25% had an initial CD4 count above 500. The most frequent comorbid illnesses were depression (34%), substance use (33%), psychiatric problems (26%), hypertension (23%), and liver disease or HCV infection (16%). Only 2% had cardiovascular or cerebrovascular disease.
Age, antiretroviral use before triple therapy, and hypertension had no impact on first-line regimen choice. Compared with MSM, women were half as likely to start with an NNRTI versus another regimen (adjusted odds ratio [aOR] 0.5, 95% confidence interval [CI] 0.3 to 0.7). People with depression (aOR 0.6, 95% CI 0.5 to 0.8) or liver disease/HCV (aOR 0.6, 95% CI 0.4 to 0.9) were 40% less likely to start with an NNRTI than with another regimen.
Reflecting the NNRTI results, women proved twice as likely as MSM to start a PI versus a non-PI regimen (aOR 2.1, 95% CI 1.5 to 3.0), and people with depression were 50% more likely to start a PI than another regimen (aOR 1.5, 95% CI 1.2 to 1.9). People with depression were almost twice as likely to start raltegravir as a nonraltegravir combination (aOR 1.9, 95% CI 1.2 to 3.0). And people with cardiovascular or cerebrovascular disease were almost 3 times as likely to start raltegravir (aOR 2.7, 95% CI 1.2 to 5.7).
Advice to avoid pregnancy when taking efavirenz and its well-appreciated psychiatric and hepatic side effects probably explain why prescribers shy away from NNRTIs for women and people with depression or liver disease. Avoidance of efavirenz in women and people with depression contributes to preferred use of PI regimens in these groups. The potential negative impact of PIs and NNRTIs on lipids probably led clinicians to favor first-line raltegravir for people with cardiovascular disease when it got licensed.
"As more choices for HIV therapy become available," the CNICS investigators suggested, "factors that impact initial regimen selection will likely become even more heterogeneous over time."
1. Saag M, Westfall A, Cole S, et al. Factors associated with the selection of initial antiretroviral therapy: real-world channeling. IDWeek 2014. October 8-12, 2014, Philadelphia. Abstract 1555.