Low-level HIV-1 viraemia in patients on HAART: risk factors and management in clinical practice.
OBJECTIVE
Characterization of the conditions favouring HIV-1 low-level viraemia (LLV) during treatment is required to guide strategies for prevention and cure.


METHODS
The characteristics and treatments of 171 patients experiencing a confirmed LLV of 50-1000 copies/mL (PLLVs) were compared with those of 146 patients with persistently controlled viraemia. We analysed the risk factors for LLV, the parameters affecting the level of viraemia and the presence of resistance-associated mutations (RAMs). We compared outcomes for PLLVs on fully effective HAART as a function of treatment modifications.


RESULTS
LLV was <500 copies/mL in at least 90% of cases. A higher zenith viral load (VL) (5.27 versus 4.91 log10 copies/mL, OR 2.23; P = 0.0003), a shorter time on continuous HAART (4.3 versus 6.8 years, OR 0.88; P = 0.0003) and previously detected RAMs (43% versus 23%, OR 2.42; P = 0.0033) were independent predictors of LLV. NNRTIs were less frequently used in PLLVs and were associated with more stable treatment. The presence of any RAM during LLV was associated with a lower zenith VL and a higher LLV. In the absence of resistance, virological success was achieved in similar proportions of patients with and without treatment modification.


CONCLUSIONS
Viraemia >500 copies/mL should no longer be considered to be LLV. In patients with a high zenith VL, several years on continuous HAART may be required to decrease the HIV reservoir and prevent LLV. Resistance testing is useful to detect RAMs, leading if necessary to treatment modifications. In the absence of resistance, treatment changes seemed dispensable.
INSERM, UMR S_1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Virologie, Paris, France marc.wirden@psl.aphp.fr.
Marc
M
Wirden
INSERM, UMR S_1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Virologie, Paris, France.
Eve
E
Todesco
INSERM, UMR S_1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Maladies Infectieuses, Paris, France.
Marc-Antoine
MA
Valantin
INSERM, UMR S_1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Virologie, Paris, France.
Sidonie
S
Lambert-Niclot
AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Médecine Interne, Paris, France.
Anne
A
Simon
INSERM, UMR S_1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Maladies Infectieuses, Paris, France.
Ruxandra
R
Calin
INSERM, UMR S_1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Maladies Infectieuses, Paris, France.
Roland
R
Tubiana
AP-HP, Groupe Hospitalier X Bichat-C Bernard, laboratoire de toxicologie, Paris, France.
Gilles
G
Peytavin
INSERM, UMR S_1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Maladies Infectieuses, Paris, France.
Christine
C
Katlama
INSERM, UMR S_1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Virologie, Paris, France.
Vincent
V
Calvez
INSERM, UMR S_1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Virologie, Paris, France.
Anne-Genevieve
AG
Marcelin
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia
D044966:Anti-Retroviral Agents
HIV; highly active antiretroviral therapy; low-level viraemia; resistance-associated mutations; treatment failure