Association of raltegravir use with long-term health outcomes in HIV-infected patients: an observational post-licensure safety study in a large integrated healthcare system

Figures & data

Table 1 Patient characteristics by cohort

Total N	Raltegravir cohort		Historical cohort		Concurrent cohort
	N	%	N	%	N	%
No. of patients and column %	1,757	100	2,542	100	3,920	100
Gender
Female	204	11.61	263	10.35	419	10.69
Male	1,553	88.39	2,279	89.65	3,501	89.31
Age Group (years)
18–29	65	3.70	139	5.47	508	12.96
30–39	172	9.79	538	21.16	871	22.22
40–49	535	30.45	1,003	39.46	1,368	34.90
50–59	617	35.12	620	24.39	815	20.79
60+	368	20.94	242	9.52	358	9.13
Race/Ethnicity
White	979	55.72	1,247	49.06	1,603	40.89
Asian and PI	93	5.29	102	4.01	239	6.10
Latino	345	19.64	628	24.70	1,049	26.76
Black	290	16.51	468	18.41	782	19.95
Other/Unknown	50	2.85	97	3.82	247	6.30
HIV transmission risk group
MSM	1,152	65.57	1,580	62.16	2,569	65.54
IDU	76	4.33	116	4.56	147	3.75
Heterosexual	280	15.94	447	17.58	737	18.80
Other/Unknown	249	14.17	399	15.70	467	11.91
Year KP HIV care started
<1990	106	6.03	81	3.20	56	1.42
1990–1994	467	26.58	400	15.70	209	5.33
1995–1999	423	24.08	496	19.50	417	10.64
2000–2004	288	16.39	760	29.90	631	16.10
2005–2009	270	15.37	803	31.60	1,542	39.34
2010–2013	203	11.55	–	–	1,065	27.17
Viral load (copies/mL)
<500	1,062	60.44	736	28.95	1,010	25.77
500–9,999	241	13.72	370	14.56	638	16.28
≥10,000	440	25.04	1,369	53.86	2,178	55.56
No test	14	0.80	67	2.64	94	2.40
CD4 count (cells/μL)
<100	116	6.60	388	15.26	447	11.40
100–199	160	9.11	393	15.46	403	10.28
200–349	413	23.51	799	31.43	1,004	25.61
350–499	380	21.63	399	15.70	859	21.91
≥500	675	38.42	508	19.98	1,136	28.98
No test	13	0.74	55	2.16	71	1.81
Time (years) since 1st ARV tx*
0–1.9	173	9.85	177	6.96	230	5.87
2–4.9	132	7.51	226	8.89	149	3.80
5–9.9	211	12.01	529	20.81	363	9.26
10+	998	54.80	536	21.09	634	16.17
No ARVs prior to entry	243	13.83	1,074	42.25	2,544	64.90
Regimen experience
1st cART Regimen	352	20.03	1,362	53.58	2,960	75.51
2nd cART Regimen	435	24.76	766	30.13	728	18.57
3rd + cART Regimen	970	55.21	414	16.29	232	5.92

* For KPSC best available date.

Table 2 Unadjusted incidence rates for health outcomes of interest (HOI)

	Raltcgravir cohort			Historical cohort			Concurrent cohort
	Number of events	Incidence rate per 1,000 years	95% confidence interval	Number of events	Incidence rate per 1,000 years	95% confidence interval	Number of events	Incidence rate per 1,000 years	95% confidence interval
Any HOI (not death)	406	102.6	92.6–112.6	438	148.7	134.8–162.6	867	104.8	97.9–111.8
Hepatic Events	84	21.7	17.1–26.4	81	26.8	20.9–32.6	165	18.0	15.2–20.7
Skin Events	165	70.6	59.9–81.4	211	90.0	77.8–102.1	537	83.4	76.4–90.5
Cardiovascular Events	31	7.3	4.7–9.9	21	6.6	3.8–9.5	40	4.1	2.8 –5.4
Lipodystrophy	73	25.8	19.9–31.7	108	38.5	31.3–45.8	86	9.4	7.4–11.4
AIDS Defining Malginancy	59	14.4	10.7–18.1	29	9.3	5.9–12.7	92	9.8	7.8–11.8
Non-AIDS Defining Malginancy	83	19.3	15.2–23.5	25	7.8	4.7–10.8	88	9.1	7.2–11.0
Muscle Events	16	7.3	4.7–9.9	11	3.4	1.4–5.4	15	1.5	0.7–2.3
Mortality	81	16.9	13.2–20.6	61	18.4	13.7–23.0	79	7.8	6.1–9.6

Figure 1 Adjusted hazard ratios comparing members of the Raltegravir cohort to each control group for each health outcome of interest.

Figure 2 Adjusted hazard ratios comparing members of the Raltegravir cohort to the historical cohort for the health outcomes of interest that had statistically significant differences when stratified by regimen number.

Table 3 Adjusted hazard ratios of health outcomes of interest

	Raltegravir cohort compared to historical cohort			Raltegravir cohort compared to concurrent cohort
	Hazard Ratio^a			Hazard Ratio^a
	Ratio	95% CI	p value	Ratio	95% CI	p value
Hepatic events	0.92	0.61–1.39	0.69	1.25	0.89–1.75	0.20
Regimen level
1st Regimen	1.06	0.56–2.01	0.85	1.14	0.67–1.93	0.63
2nd Regimen	0.77	0.37–1.57	0.47	1.48	0.81–2.71	0.21
3rd + Regimen	1.04	0.39–2.77	0.94	1.03	0.53–2.02	0.92
Skin events	1.30	0.99–1.71	0.06	1.12	0.90–1.39	0.30
Regimen level
1st Regimen	1.27	0.87–1.87	0.22	0.90	0.65–1.25	0.53
2nd Regimen	1.41	0.77–2.56	0.26	1.42	0.90–2.24	0.14
3rd + Regimen	1.63	0.89–2.96	0.11	1.16	0.73–1.85	0.53
AIDS-defining malignancies	2.69	1.53–4.71	0.00	1.85	1.21–2.82	0.00
Regimen level
1st Regimen	3.08	1.46–6.50	0.00	1.96	1.11–3.45	0.02
2nd Regimen	2.21	0.45–10.84	0.33	1.24	0.51–3.03	0.63
3rd + Regimen	2.61	0.80–8.51	0.11	2.13	0.80–5.63	0.13
Non-AIDS-Defining Malignancies	2.26	1.29–3.94	0.00	1.88	1.26–2.78	0.00
Regimen level
1st Regimen	5.35	1.87–15.25	0.00	1.94	1.08–3.51	0.03
2nd Regimen	1.11	0.36–3.44	0.86	1.44	0.67–3.08	0.35
3rd + Regimen	1.75	0.74–4.11	0.20	2.12	0.98–4.62	0.06
Cardiovascular events	1.23	0.57–2.66	0.60	0.95	0.51–1.75	0.86
Regimen level
1st Regimen	0.64	0.13–3.10	0.58	0.72	0.17–3.09	0.65
2nd Regimen	1.42	0.25–8.23	0.69	0.38	0.10–1.41	0.15
3rd + Regimen	0.79	0.21–2.98	0.73	2.24	0.50–10.07	0.29
Lipodystrophy	0.50	0.33–0.74	0.00	1.70	1.14–2.53	0.01
Regimen level
1st Rcguncn	1.21	0.56–2.60	0.63	2.46	1.29–4.70	0.01
2nd Regimen	0.47	0.23–0.95	0.03	1.28	0.67–2.42	0.46
3rd + Regimen	0.33	0.18–0.63	0.00	1.67	0.76–3.70	0.20
Mortality	0.78	0.48–1.27	0.32	1.53	1.02–2.31	0.04
Regimen level
1st Regimen	1.39	0.62–3.09	0.42	1.63	0.82–3.24	0.16
2nd Regimen	0.97	0.39–2.42	0.94	1.20	0.59–2.45	0.62
3rd + Regimen	0.46	0.20–1.04	0.06	2.00	0.83–4.84	0.13

^a Hazard Ratios by Cox Proportional Hazard Regression with stratification by PS quintile and no trimming of tails.