Objectives: Assessment of anticholinergic burden (ACB) has emerged as a clinical problem, especially in people with HIV (PWH) undergoing polypharmacy.
People with HIV and a resistant virus to all 4 classes of antiretrovirals (4DR-PWH) often require complex treatment regimens, potentially causing drug-drug interactions (DDIs).
Our objectives were to evaluate polypharmacy, ACB and DDIs in this population.

Methods: This is a cross-sectional study, including 4DR-PLWH of the PRESTIGIO Registry taking at least one non-antiretroviral drug. Polypharmacy was defined as taking ≥ 5 non-antiretroviral drugs/person. The cumulative ACB of one or more drugs with anticholinergic activity, was calculated using the ACB scale: 0= no AC effect, 1-2= low/moderate risk, ≥3= high anticholinergic risk. Characteristics of people classified according to ACB score were compared using the Kruskal-Wallis test; Spearman's correlation coefficient calculated to assess linear relationship. DDIs evaluated from the Liverpool database.⁵

Results: Overall, 172 4DR-PLWH were evaluated: 62 (27.1%) on polypharmacy, 109 (63.4%) treated with an INSTI-based regimen, 124 (72.1%) using a boosting agent and 72 (41.8%) with 4 or more antiretrovirals. Other characteristics in Table 1.
Based on ACB, 33/172 (19.2%) and 11/172 (6.4%) had a low/moderate and high AC, respectively. The most common drugs for ACB are reported in Table. 2.
The high ACB was significantly related to the number of drugs/person (r=0.327, p=<.0001) and the number of previous clinical event (r=0.222, p=0.004). Overall, we found 258 DDIs between ARVs and comedications in 115 (66.8%) PWH, and 14 (8.1%) PWH received contraindicated drug combinations (Figure 1).

Conclusions: In 4DR-PLWH, polypharmacy, and proportion of people with moderate/high AC burden were high, as well as the number of DDIs detected. As the use of boosted agents is often not avoidable in PWH with multidrug resistance, a multidisciplinary approach among specialists of different fields is strongly encouraged.

Figure 1.Summary of DDIs in the PRESTIGIO Registry

	Overall		Potential weak		Potential		Do not coadminister
Antiretroviral causing DDIs	n= 258	%	n	%	n	%	n	%
Ritonavir	115	44,6	42	16,5	65	25,2	8	3,1
Cobicistat	79	30,6	28	11,0	47	18,2	4	1,6
Etravirine	27	10,5	14	5,5	13	5,0	0	0,0
TAF/FTC or TDF/FTC	7	2,7	6	2,4	1	0,4	0	0,0
Dolutegravir	8	3,1	2	0,8	6	2,3	0	0,0
Bictegravir	3	1,2	0	0,0	3	1,2	0	0,0
Fostemsavir	7	2,7	2	0,8	5	1,9	0	0,0
Doravirine	1	0,4	1	0,4	0	0,0	0	0,0
Rilpivirine	4	1,6	2	0,8	2	0,8	0	0,0
Lamivudine	2	0,8	2	0,8	0	0,0	0	0,0
Atazanavir	3	1,2	0	0,0	1	0,4	2	0,8
Maraviroc	1	0,4	0	0,0	1	0,4	0	0,0
Zidovudina	1	0,4	0	0,0	1	0,4	0	0,0

 

Table 1. Demographic, immunologic, virologic characteristics according to ACB score.

Variable	Overall (N=172)	Score ACB ≥3 (n=11)	Score ACB=1-2 (n=33)	Score ACB=0 (n=128)	P-value
Age (years)	49.95 (45.62 – 56)	51.25 (45.34 – 55.2)	49.87 (46.28 – 56)	49.82 (45.47 – 54)	0.726
Male Gender	130 (75.6%)	10 (90.9%)	26 (78.8%)	94 (73.4%)	0.386
ART duration (years)	25.76 (22.34 – 28.7)	26.16 (19.45 – 29)	26.25 (22.34 – 29)	25.72 (22.27 – 28.4)	0.744
CD4+ cell count (cells/µL)	537 (331.5 – 818)	574 (372 - 628)	414 (326 - 740)	537 (338.5 – 843)	0.657
HIV-RNA <50 (copies/mL)	121 (70.3%)	9 (81.8%)	25 (75.8%)	87 (68%)	0.187
History of MACEs	22 (12.9%)	1 (9.1%)	10 (30.2%)	11 (8.7%)	0.114
History of Malignances	25 (14.5%)	3 (27.3%)	5 (15.2%)	17 (13.3%)	0.126
History of Hypertension	35 (20.3%)	2 (18.2%)	7 (21.2%)	26 (20.3%)	0.977
History of Neuropsychiatric diseases	39 (22.7%)	9 (81.8%)	7 (21.2%)	23 (18%)	0.0008
History of Dyslipidemia	48 (27.9%)	3 (27.3%)	10 (30.3%)	35 (27.3)	0.943

 

Table 2. Description of polypharmacy/comedication according to ACB score.

Variable	Overall (N=172)	Score ACB ≥3 (n=11)	Score ACB=1-2 (n=33)	Score ACB=0 (n=128)	P-value
Antidepressants	26 (15.1%)	10 (90.9%)	5 (15.1%)	11 (8.6%)	<0.0001
Hypercholesterolemia/ hyperlipidemia drugs	68 (39.5%)	6 (54.5%)	12 (36.4%)	50 (39.1%)	0.552
Beta-blockers	51 (29.7%)	4 (36.4%)	17 (51.5%)	30 (23.4%)	0.006
Diuretics	23 (13.3%)	1 (9.1%)	14 (42.4%)	8 (6.3%)	<.0001
Other Hypolipidemic Drugs	26 (15.1%)	2 (18.2%)	6 (18.2%)	18 (14%)	0.924
Antiplatelets	40 (23.4%)	3 (27.3%)	11 (33.3%)	26 (20.3)	0.053
Ace-inhibitors	42 (24.4%)	2 (18.2%)	6 (18.2%)	34 (26.6%)	0.536
Sartans	17 (9.9%)	1 (9.1%)	4 (12.1%)	12 (9.4%)	0.891
Calcium channel blockers	20 (11.6%)	0 (0%)	7 (21.2%)	13 (10.2%)	0.097