@article{fdi:010070973,
  title = {{B}oosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for {HIV}-1-infected patients in sub-{S}aharan {A}frica ({ANRS}12 286/{MOBIDIP}) : a multicentre, randomised, parallel, open-label, superiority trial},
  author = {{C}iaffi, {L}. and {K}oulla-{S}hiro, {S}. and {S}awadogo, {A}. {B}. and {N}dour, {C}. {T}. and {E}ymard-{D}uvernay, {S}abrina and {M}bouyap, {P}. {R}. and {A}yangma, {L}. and {Z}oungrana, {J}. and {G}ueye, {N}. {F}. {N}. and {D}iallo, {M}. and {I}zard, {S}uzanne and {B}ado, {G}. and {K}ane, {C}. {T}. and {A}ghokeng {F}obang, {A}velin and {P}eeters, {M}artine and {G}irard, {P}. {M}. and {L}e {M}oing, {V}. and {R}eynes, {J}. and {D}elaporte, {E}. and {MOBIDIP} {S}tudy {G}roup},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {D}espite satisfactory efficacy of {WHO}-recommended second-line antiretroviral treatment for patients with {HIV} in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. {W}e compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy ({ART}). {M}ethods {W}e did a multicentre, randomised, parallel, open-label, superiority, trial in the {HIV} services of five hospitals in sub-{S}aharan {A}frica ({Y}aounde, {C}ameroon; {D}akar, {S}enegal; and {B}obo {D}ioulasso, {B}urkina {F}aso). {W}e recruited patients from the long-term, post-trial cohort of the {ANRS} 12169/2{LADY} study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. {P}articipants for our study were {HIV}-1 infected with multiple mutations including {M}184{V}, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors ({NRTI}) for at least 48 weeks with at least 48 weeks follow-up in the 2{LADY} trial, with two viral load measurements of less than 200 copies per m{L} in the previous 6 months, {CD}4 counts of more than 100 cells per mu {L}, adherence of at least 90%, and no change to {ART} in the past 3 months. {W}e randomly assigned participants (1: 1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). {C}omputer-generated randomisation was stratified by study site and viral load at screening (< 50 copies per m{L}, and 50-200 copies per m{L}), and concealed from study personnel throughout the inclusion period. {A}fter randomisation, treatment allocation was not masked from clinicians or patients]. {P}atients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per m{L} at any visit, {NRTI} (tenofovir and lamivudine) were reintroduced into treatment. {T}he primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per m{L}, reintroduction of {NRTI}, or interruption of boosted protease inhibitor. {W}e designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. {T}his study is registered with {C}linical{T}rials.gov, number {NCT}01905059. {F}indings {B}etween {M}arch 5, 2014, and {J}an 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). {A}t week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. {A}t this point, treatment failure occurred in four (3.0%; 95% {CI} 0.8-7.6) of 132 participants on dual therapy and 33 (24.8%; 17.7-33.0) of 133 participants on monotherapy (relative risk 8.2, 95% {CI} 3.0-22.5; odds ratio 10.6, 95% {CI} 3.6-42.1). {T}he difference between groups (21.8%, 95% {CI} 13.9-29.7; p< 0.0001) showed superiority of dual therapy compared with monotherapy. {W}e recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. {T}wo participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung disease of unknown cause). {I}nterpretation {A}fter viral suppression with boosted protease inhibitor plus {NRTI} in second-line {ART}, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of {M}184{V} mutations at first-line treatment failure. {R}esults indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients.},
  keywords = {{AFRIQUE} {SUBSAHARIENNE} ; {YAOUNDE} ; {CAMEROUN} ; {DAKAR} ; {SENEGAL} ; {BOBO} {DIOULASSO} ; {BURKINA} {FASO}},
  booktitle = {},
  journal = {{L}ancet {HIV}},
  volume = {4},
  numero = {9},
  pages = {{E}384--{E}392},
  ISSN = {2352-3018},
  year = {2017},
  DOI = {10.1016/s2352-3018(17)30069-3},
  URL = {https://www.documentation.ird.fr/hor/fdi:010070973},
}