Safety of monitoring antiretroviral therapy response in HIV-1 infection using CD4+ T cell count at long-term intervals

Vogler, Ingridt Hildegard; Alfieri, Daniela Frizon; Gianjacomo, Heloisa Damazio Bruna; Almeida, Elaine Regina Delicato de; Reiche, Edna Maria Vissoci

doi:10.1590/0102-311X00009618

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ARTICLE • Cad. Saúde Pública 34 (10) • 2018 • https://doi.org/10.1590/0102-311X00009618 copy

Safety of monitoring antiretroviral therapy response in HIV-1 infection using CD4+ T cell count at long-term intervals

Segurança do monitoramento da resposta à terapia antirretroviral em pacientes com infecção pelo HIV-1 através da contagem de linfócitos T CD4+ a intervalos mais longos

Seguridad en la monitorización de la respuesta a la terapia antirretroviral ante el VIH-1, usando el recuento celular CD4+ T en intervalos a largo plazo

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract:

The latest Brazilian guideline recommended the reduction of routine CD4+ T cell counts for the monitoring of patients with human immunodeficiency virus type 1 (HIV-1) under combination antiretroviral therapy (cART). The aim of this study was to evaluate the safety of monitoring response to cART in HIV-1 infection using routine viral load at shorter intervals and CD4+ T cell count at longer intervals. CD4+ T cell counts and HIV-1 viral load were evaluated in 1,906 HIV-1-infected patients under cART during a three-year follow-up. Patients were stratified as sustained, non-sustained and non-responders. The proportion of patients who showed a CD4+ T > 350cells/µL at study entry among those with sustained, non-sustained and non-responders to cART and who remained with values above this threshold during follow-up was 94.1%, 81.8% and 71.9%, respectively. HIV-1-infected patients who are sustained virologic responders and have initial CD4+ T cell counts > 350cells/µL showed a higher chance of maintaining the counts of these cells above this threshold during follow-up than those presenting CD4+ T ≤ 350cells/µL (OR = 39.9; 95%CI: 26.5-60.2; p < 0.001). This study showed that HIV-1-infected patients who had sustained virologic response and initial CD4+ T > 350cells/µL were more likely to maintain CD4+ T cell counts above this threshold during the next three-year follow-up. This result underscores that the evaluation of CD4+ T cell counts in longer intervals does not impair the safety of monitoring cART response when routine viral load assessment is performed in HIV-1-infected patients with sustained virologic response.

Keywords:
CD4 Lymphocyte Count; HIV-1; Highly ActiveAntiretroviral Therapy; Viral Load

Variables	All patients (N = 1,906)		Virologic response						p-value
	All patients (N = 1,906)		Sustained * (n = 1,174)		Non-sustained ** (n = 325)		Non-responder *** (n = 407)
	n	%	n	%	n	%	n	%
Age (years)
15-29	169	8.9	67	5.7 ^a	39	12.0 ^b	63	15.5 ^b	< 0.001 ^#
30-39	519	27.2	283	24.1 ^a	83	25.5 ^a	153	37.6 ^b
40-49	630	33.1	405	34.5 ^a	102	31.4 ^a	123	30.2 ^a
≥ 50	588	30.8	419	35.7 ^a	101	31.1 ^a	68	16.7 ^b
Time of diagnosis (years)
< 5	659	34.6	388	33.0 ^a	124	38.2 ^a	147	36.1 ^a	0.116
5-9	593	31.1	381	32.5 ^a	86	26.5 ^b	126	31.0 ^a,b
10-14	473	24.8	292	24.9 ^a	76	23.4 ^a	105	25.8 ^a
≥ 15	181	9.5	113	9.6 ^a,b	39	12.0 ^a	29	7.1 ^b
Time under cART (years)
< 5	887	46.5	523	44.5 ^a	164	50.5 ^a	200	49.1 ^a	0.129
5-9	518	27.2	338	28.8 ^a	73	22.5 ^b	107	26.3 ^a,b
10-14	402	21.1	245	20.9 ^a	71	21.8 ^a	86	21.1 ^a
≥ 15	99	5.2	68	5.8 ^a	17	5.2 ^a	14	3.4 ^a
Sex
Female	918	48.2	529	45.1 ^a	177	54.5 ^b	212	52.1 ^b	0.002 ^#
Male	988	51.8	645	54.9 ^a	148	45.5 ^b	195	47.9 ^b
Ethnicity
Caucasian	1,459	76.5	911	77.6 ^a	245	75.4 ^a	303	74.4 ^a	0.374
Non-Caucasian	447	23.5	263	22.4 ^a	80	24.6 ^a	104	25.6 ^a
Educational level (years)
None	36	1.9	27	2.3 ^a	2	0.6 ^a	7	1.8 ^a	0.026 ^#
1-3	237	12.4	137	11.9 ^a	51	16.2 ^b	49	12.3 ^a,b
4-7	855	44.9	525	45.5 ^a	137	43.6 ^a	193	48.5 ^a
8-11	524	27.5	314	27.2 ^a	91	29.0 ^a	119	29.9 ^a
≥ 12	213	11.2	150	13.0 ^a	33	10.5 ^a,b	30	7.5 ^b
Not known	41	2.1
Municipality of residence ^##
Small	540	28.3	331	28.2 ^a	93	28.6 ^a	116	28.5 ^a	0.826
Medium	239	12.5	143	12.2 ^a	47	14.5 ^a	49	12.0 ^a
Large	1,127	59.1	700	59.6 ^a	185	56.9 ^a	242	59.5 ^a
CD4+ T count (cells/µL)
Baseline (2012)
< 200	174	9.1	37	3.2 ^a	21	6.5 ^b	116	28.5 ^c	< 0.001 ^#
200-350	312	16.4	156	13.3 ^a	57	17.5 ^a	99	24.3 ^b
351-500	425	22.3	255	21.7 ^a	86	26.5 ^a	84	20.6 ^a
> 500	995	52.2	726	61.8 ^a	161	49.5 ^b	108	26.5 ^c
Follow-up (2013-2015)
< 200	130	6.8	18	1.5 ^a	13	4.0 ^b	99	24.3 ^c	< 0.001 ^#
200-350	246	12.9	94	8.0 ^a	49	15.1 ^b	103	25.3 ^c
351-500	351	18.4	196	16.7 ^a	75	23.1 ^b	80	19.7 ^a,b
> 500	1,179	61.9	866	73.8 ^a	188	57.8 ^b	125	30.7 ^c
CD4+ T slope (cells/µL/year)
< -100	160	8.4	93	7.9 ^a	36	11.1 ^a	31	7.6 ^a	0.001*
-99 to 0	632	33.2	358	30.5 ^a	113	34.8 ^a,b	161	39.6 ^b
+1 to +99	810	42.5	507	43.2 ^a	134	41.2 ^a	169	41.5 ^a
> +100	304	15.9	216	18.4 ^a	42	12.9 ^b	46	11.3 ^b

Sustained responder * (reference outcome group)	Non-sustained responder **		Non-responder ***
Sustained responder * (reference outcome group)	OR (95CI)	p-value	OR (95%CI)	p-value
Age (years)
15-29	2.57 (1.58-4.19)	< 0.001	8.52 (5.05-14.35)	< 0.001
30-39	1.25 (0.88-1.78)	0.216	4.04 (2.74-5.95)	< 0.001
40-49	1.04 (0.75-1.43)	0.831	2.03 (1.39-2.98)	< 0.001
≥ 50	1.00		1.00
Time of diagnosis (years)
< 5	0.48 (0.23-1.02)	0.055	0.97 (0.40-2.36)	0.946
5-9	0.47 (0.23-0.96)	0.038	1.17 (0.51-2.72)	0.710
10-14	0.52 (0.29-0.94)	0.031	1.14 (0.54-2.41)	0.723
≥ 15	1.00		1.00
Time on cART (years)
< 5	2.35 (0.94-5.84)	0.066	1.04 (0.35-3.08)	0.945
5-9	1.79 (0.74-4.35)	0.197	1.03 (0.36-2.97)	0.956
10-14	1.98 (0.91-4.33)	0.085	1.33 (0.50-3.52)	0.572
≥ 15	1.00		1.00
Sex
Male	1.00		1.00
Female	1.49 (1.15-1.93)	0.003	1.56 (1.19-2.05)	0.001
Educational level (years)
None	0.37 (0.08-1.68)	0.199	1.50 (0.50-4.52)	0.470
1-3	1.65 (0.98-2.77)	0.059	1.66 (0.92-3.02)	0.094
4-7	1.13 (0.73-1.76)	0.569	1.62 (0.99-2.64)	0.055
8-11	1.33 (0.84-2.09)	0.225	1.72 (1.03-2.86)	0.039
≥ 12	1.00		1.00
CD4+ T count (cells/µL)
Baseline (2012)
< 200	1.77 (0.79-3.95)	0.162	3.40 (1.66-6.94)	0.001
200-350	1.17 (0.68-1.99)	0.574	1.55 (0.90-2.66)	0.117
351-500	1.36 (0.94-1.97)	0.100	1.55 (1.03-2.33)	0.037
> 500	1.00		1.00
Follow-up (2013-2015)
< 200	1.93 (0.70-5.29)	0.201	18.82 (8.29-42.74)	< 0.001
200-350	2.11 (1.20-3.73)	0.010	5.98 (3.44-10.40)	< 0.001
351-500	1.58 (1.07-2.35)	0.022	2.37 (1.56-3.62)	< 0.001
> 500	1.00		1.00
CD4+ T slope (cells/µL/year)
< -100	2.13 (1.21-3.74)	0.009	1.76 (0.94-3.30)	0.077
-99 to 0	1.55 (0.99-2.42)	0.052	1.29 (0.80-2.08)	0.293
+1 to +99	1.20 (0.80-1.81)	0.381	1.05 (0.68-1.61)	0.833
> +100	1.00		1.00

Virologic response/Initial CD4 count (cells/µL)	Outcome CD4⁺ T cell count				Total		OR (95%CI)	p-value
	< 350cells/µL		> 350cells/µL
	n	%	n	%	n	%
Male patients
Sustained *
≤ 350	87	72.5	33	27.5	120	100.0
> 350	38	7.2	487	92.8	525	100.0	33.8 (20.1-56.8)	< 0.001
Non-sustained **
≤ 350	30	81.1	7	18.9	37	100.0
> 350	18	16.2	93	83.8	111	100.0	22.1 (8.4-58.1)	< 0.001
Non-responder ***
≤ 350	102	91.1	10	8.9	112	100.0
> 350	25	30.1	58	69.9	83	100.0	23.7 (10.6-52.7)	< 0.001
Total	300	30.4	688	69.6	988	100.0
Female patients
Sustained *
≤ 350	51	69.9	22	30.1	73	100.0
> 350	20	4.4	436	95.6	456	100.0	50.5 (25.8-98.9)	< 0.001
Non-sustained **
≤ 350	33	80.5	8	19.5	41	100.0
> 350	27	19.9	109	80.1	136	100.0	16.6 (6.9-40.1)	< 0.001
Non-responder ***
≤ 350	89	86.4	14	13.6	103	100.0
> 350	29	26.6	80	73.4	109	100.0	17.5 (8.6-35.5)	< 0.001
Total	249	27.1	669	72.9	918	100.0
All patients
Sustained *
≤ 350	138	71.5	55	28.5	193	100.0
> 350	58	5.9	923	94.1	981	100.0	39.9 (26.5-60.2)	< 0.001
Non-sustained **
≤ 350	63	80.8	15	19.2	78	100.0
> 350	45	18.2	202	81.8	247	100.0	18.8 (9.8-36.1)	< 0.001
Non-responder ***
≤ 350	191	88.8	24	11.2	215	100.0
> 350	54	28.1	138	71.9	192	100.0	20.3 (12.0-34.5)	< 0.001
Total	549	28.8	1,357	71.2	1906	100.0

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[1] Correspondence E. M. V. Reiche Departamento de Patologia, Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Estadual de Londrina. Av. Robert Koch 60, Londrina, PR 86038-440, Brasil. reiche@sercomtel.com.br