Is HIV-1 viraemia below 20 copies/mL in antiretroviral-treated patients associated with virologic outcome?

Figures & data

Figure 1. Flowchart patient inclusion.

Table 1. Overview of baseline characteristics of patients included in the study.

Total number of patients	1341 (100.0%)
Male gender	1000 (74.6%)
Age (mean years)	47.4 (SD 11.7)
Region of birth
Europe	813 (60.6%)
Sub-Saharan Africa	206 (15.4%)
Latin America^a	220 (16.4%)
Other	102 (7.6%)
Risk group
MSM	754 (56.2%)
Heterosexual (male)	180 (13.4%)
Heterosexual (female)	274 (20.4%)
IV drug user	42 (3.1%)
Other	91 (6.8%)
Years from HIV diagnosis (mean)^b	10.0 (SD 6.9)
Nadir CD4+ cell count (cells/mm^3)
<200	593 (44.7%)
200–499	631 (47.6%)
≥500	103 (7.8%)
T0 CD4+ cell count (mean cells/mm^3)^c	692 (SD 281)
Years of uninterrupted ART (mean)^d	6.9 (SD 5.4)
ART regimen
NVP + NRTIs	397 (29.6%)
RPV + NRTIs	254 (18.9%)
DTG + NRTIs	199 (14.8%)
EFV + NRTIs	188 (14.0%)
PI+/−NRTIs	154 (11.5%)
DTG-mono+/−3TC	95 (7.1%)
EVG-COBI + NRTIs	32 (2.4%)
Other	22 (1.6%)

ART: antiretroviral therapy; DTG: dolutegravir; EFV: efavirenz; EVG-COBI: elvitegravir-cobicistat; IV drug user: intravenous drug user; MSM: men who have sex with men; NL: Netherlands; NRTIs: nucleoside reverse transcriptase inhibitors; NVP: nevirapine; PI: protease inhibitor; RPV: rilpivirine; T0: time of first HIV RNA measurement on or after 21-01-2016; 3TC: lamivudine.

^a Including the Antilles and Suriname.

^b Years from HIV diagnosis until 21-01-2016.

^c First CD4+ cell count on or after 21-01-2016. If no CD4+ cell count was available during follow-up, the most recent CD4+ cell count prior to 21-01-2016 was selected.

^d Time (years) until 21-01-2016.

Table 2. Univariate and multivariate logistic regression results: patient, laboratory, and therapy characteristics, stratified by VL, that is, negative (n = 958) or positive (n = 383) at T0.

	Univariate analysis		Multivariate analysis
	All patients		All patients
	positive HIV-1-RNA PCR at T0	p Value	positive HIV-1-RNA PCR at T0	p Value
	OR (95% CI)		OR (95% CI)
ART regimen^a
NVP + NRTIs	1.000	Reference	1.000	Reference
RPV + NRTIs	1.350 (0.957–1.904)	.088	1.041 (0.722–1.501)	.828
DTG + NRTIs	1.229 (0.845–1.788)	.281	0.797 (0.533–1.192)	.269
EFV + NRTIs	1.008 (0.680–1.493)	.970	0.809 (0.538–1.215)	.307
PI+/-NRTIs	1.459 (0.978–2.178)	.064	1.079 (0.708–1.643)	.724
DTG-mono+/−3TC	0.606 (0.343–1.072)	.085	0.504 (0.279–0.910)	.023
EVG-COBI + NRTIs	1.088 (0.488–2.427)	.836	0.695 (0.307–1.578)	.385
Other	0.818 (0.294–2.272)	.700	0.641 (0.223–1.842)	.409
Gender
Male	1.000	Reference
Female	0.815 (0.616–1.077)	.149
Age (years)	1.001 (0.991–1.011)	.825
Region of birth
Europe	1.000	Reference
Sub-Saharan Africa	1.077 (0.772–1.502)	.662
Latin America^b	0.815 (0.580–1.146)	.239
Other	0.971 (0.616–1.533)	.900
Risk group
MSM	1.000	Reference
Heterosexual (male)	1.168 (0.825–1.656)	.381
Heterosexual (female)	0.822 (0.601–1.125)	.221
IV drug user	0.564 (0.257–1.237)	.153
Other	0.858 (0.525–1.404)	.543
Years from HIV diagnosis^c	0.990 (0.973–1.008)	.266
Nadir CD4+ cell count (cells/mm³)
<200	1.000	Reference
200-499	0.916 (0.715–1.174)	.490
≥500	0.800 (0.496–1.291)	.360
T0 CD4+ cell count (cells/mm³)^d
<500	1.000	Reference
≥500	0.798 (0.607–1.049)	.107
Pre-ART VL (copies/mL)
<1000	0.249 (0.057–1.089)	.065	0.227 (0.051–1.002)	.050
1000–9999	0.489 (0.304–0.786)	.003	0.506 (0.310–0.827)	.007
10,000–99,999	0.804 (0.626–1.033)	.088	0.850 (0.655–1.104)	.223
≥100,000	1.000	Reference	1.000	Reference
Past virological failure^e
Never	1.000	Reference
≥1x	1.236 (0.732–2.089)	.427
Years of uninterrupted ART^f	0.957 (0.935–0.979)	<.001
Years of virological suppressionfg	0.894 (0.866–0.923)	<.001	0.891 (0.861–0.921)	<.001
Past ART interruption
No	1.000	Reference
Yes	1.049 (0.792–1.389)	.739

Total no of patients = 1341.

ART: antiretroviral therapy; CI: confidence interval; DTG: dolutegravir; EFV: efavirenz; EVG-COBI: elvitegravir-cobicistat; IV drug user: intravenous drug user; MSM: men who have sex with men; NL: Netherlands; NRTIs: nucleoside reverse transcriptase inhibitors; NVP: nevirapine; OR: odds ratio; p: target detected using Cobas AmpliPrep/Cobas Taqman HIV-1 test v2.0; PI: protease inhibitor; pre-HAART: antiretroviral therapy initiated before highly active antiretroviral therapy was available RPV: rilpivirine; T0: time of first HIV RNA measurement on or after 21-01-2016; 3TC: lamivudine; VL: viral load.

^a ART regimen on 21-01-2016.

^b The category Latin America includes Suriname and the Antilles.

^c Years from HIV diagnosis until 21-01-2016.

^d First CD4+ cell count on or 21-01-2016. If no CD4+ cell count was available during follow-up, the most recent CD4+ cell count prior to 21-01-2016 was selected.

^e Virological failure (guideline definition): a confirmed VL >200 copies/mL, 24 weeks after initiating a specific ART regimen.

^f Time (years) until 21-01-2016.

^g Virological suppression is defined as continuous period of time prior to 21-01-2016 during which all VLs are below the level of quantification.

Table 3. VL at T0 and T1 (all patients with 2 VL measurements).

	Negative HIV-1-PCR signal at T0	Positive HIV-1-PCR signal at T0
VL at T1
VL < 20, Negative HIV-1-PCR signal at T0	666 (74.7%)	192 (53.6%)
VL < 20, Positive HIV-1-PCR signal at T0	178 (20.0%)	117 (32.7%)
VL ≥20	47 (5.3%)	49 (13.7%)
Total	891 (100.0%)	358 (100.0%)

No. of patients = 1249.

N: target not detected using Cobas AmpliPrep/Cobas Taqman HIV-1 test v2.0; p: target detected using Cobas AmpliPrep/Cobas Taqman HIV-1 test v2.0; T0: time of first HIV RNA measurement on or after 21-01-2016; T1: time of second HIV RNA measurement after 21-01-2016; VL: viral load.

Table 4. Univariate and multivariate logistic regression results: patient, laboratory, and therapy characteristics stratified by VL (i.e. <20 copies/mL or ≥20 copies/mL) at T1 (all patients).

	Univariate analysis		Multivariate analysis
	All patients		All patients
	OR (95% CI) VL ≥ 20 at T1	p Value	OR (95% CI) VL ≥ 20 at T1	p Value
VL at T0
Vl <20, negative HIV-1-PCR signal	1.000	Reference	1.000	Reference
VL < 20, positive HIV-1-PCR signal	2.848 (1.869–4.338)	<.001	2.291 (1.457–3.601)	<.001
Gender
Male	1.000	Reference
Female	1.453 (0.928–2.274)	.103
Age (years)	0.986 (0.968–1.004)	.125
Region of birth
Europe	1.000	Reference	1.000	Reference
Sub-Saharan Africa	2.400 (1.442–3.994)	.001	2.003 (1.132–3.543)	.017
Latin America^a	1.033 (0.547–1.951)	.921	1.031 (0.525–2.027)	.929
Other	2.043 (1.018–4.097)	.044	2.142 (1.035–4.432)	.040
Risk group
MSM	1.000	Reference
Heterosexual (male)	1.027 (0.520–2.027)	.939
Heterosexual (female)	1.611 (0.975–2.662)	.063
IV drug user	0.946 (0.219–4.080)	.941
Other	1.892 (0.918–3.899)	.084
Years from HIV diagnosis^b	0.989 (0.959–1.020)	.477
Nadir CD4+ cell count (cells/mm³)
<200	1.000	Reference
200-499	0.968 (0.626–1.495)	.883
≥500	0.902 (0.393–2.066)	.807
T0 CD4+ cell count (mean cells/mm³)^c
<500	1.000	Reference
≥500	0.929 (0.570–1.514)	.767
Pre-ART VL (copies/mL)
<100,000	0.700 (0.459–1.068)	.098	0.758 (0.482–1.192)	.230
≥100,000	1.000	Reference	1.000	Reference
Past virological failure^d
Never	1.000	Reference	1.000	Reference
≥1x	2.634 (1.328–5.224)	.006	1.939 (0.890–4.222)	.095
Years of uninterrupted ART^e	0.940 (0.901–0.982)	.005
Years of virological suppression^e^f	0.864 (0.804–0.928)	<.001	0.909 (0.846–0.976)	.009
Past ART interruption
No	1.000	Reference
Yes	1.532 (0.970–2.420)	.068
Cause ART interruption
Patient's initiative (including suspected lack of compliance)^g	3.712 (2.235–6.166)	<.001	2.315 (1.293–4.146)	.005
No interruption/other	1.000	Reference	1.000	Reference
ART change during follow-up
Yes	2.436 (1.593–3.727)	<.001	2.657 (1.671–4.226)	<.001
No	1.000	Reference	1.000	Reference
ART regimen^h
NNRTI + NRTIs	1.000	Reference	1.000	Reference
PI+/-NRTIs	2.145 (1.210–3.803)	.009	1.023 (0.531–1.972)	.945
INSTI+/-NRTIs	1.495 (0.921–2.427)	.104	0.964 (0.563–1.652)	.894
Other	0.784 (0.103–5.980)	.814	0.505 (0.060–4.274)	.531

No. of patients = 1249.

ART: antiretroviral therapy; CI: confidence interval; INSTI: integrase strand transfer inhibitor; IV drug user: intravenous drug user; MSM: men who have sex with men; N: target not detected using Cobas AmpliPrep/Cobas Taqman HIV-1 test v2.0; NL: Netherlands; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTIs: nucleoside reverse transcriptase inhibitors; OR: odds ratio; p: target detected using Cobas AmpliPrep/Cobas Taqman HIV-1 test v2.0; PI: protease inhibitor; T1: time of second HIV RNA measurement after 21-01-2016; T0: time of first HIV RNA measurement on or after 21-01-2016; VL; viral load.

^a The category Latin America includes Suriname and the Antilles.

^b Years from HIV diagnosis until 21-01-2016.

^c First CD4+ cell count on or 21-01-2016. If no CD4+ cell count was available during follow up, the most recent CD4+ cell count prior to 21-01-2016 was selected.

^d Virological failure (guideline definition): a confirmed VL >200 copies/mL, 24 weeks after initiating a specific ART regimen.

^e Time (years) until 21-01-2016.

^f Virological suppression is defined as continuous period of time prior to 21-01-2016 during which all VLs are below the level of quantification.

^g I.e. including an ART interruption imposed by the physician based on suspected lack of compliance.

^h ART regimen on 21-01-2016.