Efficacy of third-line therapy in resource-limited countries

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The ANRS THILAO cohort has provided the first evidence that third-line antiretroviral therapy is effective in sub-Saharan Africa. Run jointly by Prof Serge Eholié (ANRS Ivory Coast site, CHU de Treichville) and Dr Roland Landman, Hôpital Bichat, AP-HP, Paris, and Institut de Médecine et d'Epidémiologie Appliquée, Paris, with their colleagues at Inserm and AP-HP, this cohort also demonstrates the value of a strategy designed to identify patients in whom second-line treatment has failed, in a setting where there is limited access to measurement of viral load. These results point to a new approach to therapeutic decision-making in resource-limited countries and will be presented in an oral communication on 24 July, during the 9th Conference on HIV Science (IAS 2017), organized by the International AIDS Society and the ANRS in Paris from July 23rd to 26th 2017.

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Access to antiretroviral therapy for people living with HIV/AIDS in resource-limited countries has greatly improved in recent years, but is not yet optimal. The rising number of patients on antiretrovirals does, however, raise the increasingly urgent question of treatment failure after first- and second-line treatment. In patients in this situation, HIV resistance mutations are frequent and often involve drug cross-resistance. The question then is to know which antiretroviral therapy can be proposed third line, in a context of limited access to measurement of viral load (to identify virologic failure) and especially to genotypic tests (which identify resistance mutations).

The treatment cohort ANRS 12269-THILAO (THird Line Antiretroviral Optimization) was designed to explore a third-line therapeutic strategy in patients with virologic failure after second-line triple-drug therapy. Launched in March 2013, this study in 201 patients in four West African countries (Burkina Faso, Ivory Coast, Mali, and Senegal) was jointly overseen by Prof Serge Eholié (ANRS Ivory Coast Site, CHU de Treichville) and Dr Roland Landman, Hôpital Bichat, AP-HP, Paris, and Institut de Médecine et d'Epidémiologie Appliquée, Paris, working with their colleagues at Inserm and AP-HP. Dr Raoul Moh (ANRS Ivory Coast Site) will present the results on 24 July in an oral communication, during the 9th IAS Conference on HIV Science, organized by the International Aids Society and the ANRS in Paris.

Whether first- or second-line, the treatment of these patients was in line with World Health Organization (WHO) recommendations. Two successive interventions were planned in these patients with treatment failure. First, adherence was increased in all patients by means of a series of measures (pill organizers, phone reminders, support group, etc.). The patients continued their second-line treatment for 4 months, after which viral load was measured to decide on treatment:

  • Maintenance of second-line triple-drug therapy in patients in whom viral load is undetectable. 
  • Switch to third-line antiretroviral therapy in patients with confirmed virologic failure. The new treatment comprised the latest antiretrovirals not yet taken by the patients: darunavir boosted with ritonavir (protease inhibitors) and raltegravir (integrase inhibitor).


In both cases, the patients were followed up for an additional 48 weeks.

After the 4 months during which measures were implemented to increase adherence, 66% of the patients were able to maintain their second-line treatment, their viral load again being undetectable. “This indicates that most patients considered to be with virologic failure were not really,” explain Dr Landman and Prof Eholié. “The patients had, in fact, difficulty adhering to treatment. This led the clinicians to act on adherence before deciding on treatment.”

Among the patients who took third-line antiretroviral treatment, 62 % had an undetectable viral load after 48 weeks. No serious side effect was observed. These findings show that it is possible to achieve good efficacy with third-line antiretroviral therapy in resource-limited countries.

Prof François Dabis, Director of the ANRS, notes that the “ANRS 12269-THILAO confirms the need to improve adherence in a lasting fashion, that is to say for life. It also provides firm evidence that third-line treatments should be accessible in resource-limited countries to patients who, despite these efforts, have experienced treatment failure.”

Lastly, these results also raise questions concerning therapeutic strategy in the case of lack of viral control. Prof Eholié and Dr Landman point out that “It is essential we review the way viral load is used in resource-limited countries, so as to avoid prescription of the latest antiretroviral drugs, which are far more costly than older antiretrovirals. This is a public health challenge for all resource-limited countries.”
 

Source :
48-weeks efficacy of a third line based on darunavir plus raltegravir regimen in HIV-infected adults who failed second-line protease inhibitor based-regimen in Sub-Saharan Africa, ANRS 12269 THILAO study.
R. Moh1,2, A. Benalycherif3, D. Gabillard4, J. Lecarrou4, L. N'guessan5, A. Anzian6, D. Minta7, A. Sawadogo8, M. Seydi9, J. Drabo10, M.-L. Chaix11, P.-M. Girard12, C. Danel13,14, X. Anglaret5,14, S. Eholié5,15, R. Landman3,16, Thilao Study Group.
1Département de Dermatologie et Infectiologie, 18 BP 1954 ABIDJAN 18, ABIDJAN, Cote D'Ivoire, 2Programme PACCI/Site ANRS de Côte d'Ivoire, ABIDJAN, Cote D'Ivoire, 3Institut de Médecine et d'Epidémiologie Appliquée, Hopital Bichat, Claude Bernard, Paris, France, 4Inserm U1219, ISPED, Université Bordeaux 2, Bordeaux, Bordeaux, France, 5Programme Pacci/site ANRS de Côte d'Ivoire, ABIDJAN, Cote D'Ivoire, 6Centre de Prise en charge, de Recherche et de Formation Abidjan, ABIDJAN, Cote D'Ivoire, 7Service des Maladies Infectieuses et Tropicales, CHU Point G, ABIDJAN, Cote D'Ivoire, 8Hôpital de jour, Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso, 9SMIT/CRCF, Dakar, DAKAR, Senegal, 10Hopital Yalgado, Ouagadoudou, Ouagadougou, Burkina Faso, 11Service de Virologie, St Louis, Paris, France, 12Service des Maladies Infectieuses et Tropicales, Hôpital St Antoine, Paris, France, 13Programme Pacci/site ANRS de Côte d'Ivoire, Abidjan, Cote D'Ivoire, 14Inserm U1219, ISPED, Université Bordeaux 2, Bordeaux, France, 15Département de dermatologie et d'infectiologie, UFR Sciences médicales, ABIDJAN, Cote D'Ivoire, 16INSERM, IAME, UMR 1137, F-75018, Paris, France