Persistent Low-Level HIV-1 RNA between 20 and 50 copies/mL in Antiretroviral-

Treated Patients: Associated Factors and Virological Outcome

Dr Charlotte CHARPENTIER Laboratoire de Virologie

CHU Bichat-Claude Bernard Groupe Hospitalier « Hôpitaux Universitaires

Paris Nord Val de Seine »Université Paris Diderot - Paris 7

Poster WEPDB0102

BACKGROUND • Since the availability of viral load (VL) assay with a threshold of 20 copies/mL,

some patients display VL values between 20 and 50 copies/mL.

• The aims of our study were to: (i) identify factors associated with low-level viremia (LLV) in patients receiving

stable suppressive antiretroviral therapy (cART);(ii) assess virological outcome during the year following LLV detection.

PATIENTS AND METHODS

• Retrospective study among the 4820 patients followed in our institution fulfilling the inclusion criteria: (i) stable cART for at least 6 months; (ii) all VL <50 copies/mL; and (iii) at least 3 VL determinations during the one-year inclusion period.

• We compared patients with all VL <20 copies/mL (Group LLV-) and patients with at least 2 VL between 20 and 50 copies/mL (Group LLV+).

• All patients were then followed-up during 1 year.

RESULTS (1)• Among the 656 patients included, 38 (5.8%) were in group LLV+.• The nature of the ongoing cART did not differ between LLV- and LLV+ groups.• In the multivariate analysis, only CDC clinical stage B/C at study inclusion and a

higher “Blip Ratio” before study inclusion were independently associated with LLV.

Median [InterQuartileRange]a Group LLV- (n = 618)

Group LLV+ (n = 38)

Univariate analysis Multivariate analysis

P value Odds Ratio (95% CI)

P value

At inclusion Age (years) 44 [38-50] 47 [43-53] 0.04 Gender (% male) 61 74 0.1 CD4 cell count (/ mm3) 552 [405-738] 612 [403-734] 0.7 CD4 cell count nadir (/ mm3) 168 [69-255] 124 [26-252] 0.2 Duration since HIV diagnosis (years) 11 [7-17] 14 [6-18] 0.29 Duration of any ARV therapy (months) 92 [44-144] 127 [31-156] 0.6 Duration of ongoing ARV therapy (months) 28 [16-41] 21 [10-36] 0.054

Total number of ARV drugs received 7 [4-9] 7 [4-11] 0.4 Number of virological failures* 1 [0-2] 1 [0-2] 0.32 Ongoing ARV-based treatment n (%) - 2 NRTI + 1 PI/ r - 2 NRTI + 1 NNRTI

302 (49%) 211 (34%)

19 (50%) 9 (24%)

0.23

Duration of HIV-1 RNA values <50 copies/ mL before inclusion (months) 9 [3-23] 7 [2-17] 0.047

CDC stage (%) A B/ C

56 44

32 68

0.004

2.9 [1.4-5.9]

0.003

At initiation of ongoing ARV therapy HIV-1 RNA level (log10 copies/ mL) 1.7 [1.7-3.4] 2.0 [1.7-4.5] 0.02 CD4 cell count (/ mm3) 402 [262-587] 254 [142-583] 0.02 Blip Ratio (%) b 0 [0-8] 6 [0-13] 0.007 0.9 [0.9-1.0] 0.001 At initiation of first line ARV therapy HIV-1 RNA level (log10 copies/ mL) 4.6 [3.7-5.3] 4.8 [4.5-5.1] 0.7 CDC stage (%) A B/ C

70 30

47 53

0.006

CD4 cell count (/ mm3) 228 [122-346] 204 [48-310] 0.3

“Blip Ratio” was defined as: (number of VL >50 copies/mL)/(number of VL determinations)

CONCLUSIONS• LLV was infrequent in our series and the one-year follow-up did not evidence a

higher rate of virological failure than in patients always fully-suppressed. • LLV seems to be a transient phenomenon that might be driven by residual

ongoing viral replication and/or viral release and/or accuracy of VL assay in lower values.

• These results suggest that LLV should not drive therapeutic modifications. However, clinical trials to assess potential benefit of therapeutic interventions in patients exhibiting persistent LLV between 20 and 50 copies/mL are needed to establish the management of these patients.

Group LLV- (n = 413)

Group LLV+ (n = 25) P value

All HIV-1 RNA values <20 copies/mL (%) 65 44 0.053

2 HIV-1 RNA values between 20 and 50 copies/mL (%) 2 16 0.002

2 consecutive HIV-1 RNA values > 50 copies/mL (%) 4 8 0.320

Blip Ratio (%, IQR) 0 (0-0) 0 (0-25) 0.070

RESULTS (2)• During the follow-up period, the proportion of patients experiencing virological

failure was not different between the 2 groups • During the follow-up period 40% of patients shifted from LLV+ to LLV- status.