Switching the third drug of antiretroviral therapy to maraviroc in aviraemic subjects: a pilot, prospective, randomized clinical trial.
OBJECTIVE
To evaluate the safety and efficacy of switching the third drug of antiretroviral treatment to maraviroc in aviraemic subjects infected with R5 HIV.


METHODS
This is a pilot, prospective, randomized clinical trial (ClinicalTrials ID: NCT00966329). Eighty HIV-1-infected aviraemic adults on stable antiretroviral treatment for ≥1 year and no antiretroviral drug resistance were screened for the presence of non-R5 HIV by triplicate proviral V3 population sequencing. From them, 30 subjects with R5 HIV-1 were randomized 1 : 1 to switch the non-nucleoside reverse transcriptase inhibitor or ritonavir-boosted protease inhibitor to maraviroc (n = 15) or to continue the same antiretroviral treatment (controls, n = 15). The principal endpoint was the proportion of subjects with HIV-1 RNA <50 copies/mL at week 48. Ultrasensitive proviral HIV-1 tropism testing (454 sequencing) was performed retrospectively at weeks 0, 4, 12, 24, 36 and 48.


RESULTS
One subject in the maraviroc arm and one control had non-R5 HIV in proviral DNA by retrospective 454 sequencing. The subject receiving maraviroc was the only individual to develop virological failure. However, plasma HIV at failure was R5. Switching to maraviroc was well tolerated and associated with small, but statistically significant, declines in total, high-density lipoprotein and low-density lipoprotein cholesterol. Median (IQR) triglyceride [1 (0.67-1.22) versus 1.6 (1.4-3.1) mmol/L, P = 0.003] and total cholesterol [4.3 (4.1-4.72) versus 5.4 (4-5.7) mmol/L, P = 0.059] values were lower in the maraviroc arm than in controls at week 48.


CONCLUSIONS
In this pilot, prospective, randomized clinical trial, switching the third drug to maraviroc was safe, efficacious and improved lipid parameters.
HIV Unit & Fundació Lluita contra la SIDA, Hospital Universitari Germans Trias i Pujol, Barcelona, Catalonia, Spain. abonjoch@flsida.org
Anna
A
Bonjoch
Christian
C
Pou
Núria
N
Pérez-Álvarez
Rocío
R
Bellido
Maria
M
Casadellà
Jordi
J
Puig
Marc
M
Noguera-Julian
Bonaventura
B
Clotet
Eugènia
E
Negredo
Roger
R
Paredes
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000627:therapeutic use*; D050171:Dyslipidemias / Q000097:blood / Q000150:complications; D005260:Female; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D014230:Triazoles / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D056189:Viral Tropism / Q000187:drug effects
D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D000960:Hypolipidemic Agents; D014230:Triazoles; D014280:Triglycerides; D000077592:Maraviroc
HIV; ultrasensitive proviral HIV-1 tropism testing; virally suppressed patients