ANRS 130 Apollo: improving triple therapy in cases of severe immunodeficiency

The Apollo study: fighting HIV-1

The aim of the Apollo study is to investigate whether enfuvirtide (ENF) added to basic combination antiretroviral therapy (cART) improves the CD4 cell count response at week 24 in treatment-naive patients with advanced HIV disease.

The primary objective of the trial is to study the immunological efficacy at week 24 of an induction-maintenance strategy using initial intensification of antiretroviral triple therapy with enfuvirtide. The efficacy of this strategy is being evaluated in a randomised manner in HIV-1-infected patients who are antiretroviral-naive and have severe immunodeficiency leading to a high risk of clinical disease progression. These patients receive a combination of antiretroviral drugs including emtricitabine/tenofovir disoproxil fumarate, efavirenz or lopinavir/ritonavir, initially intensified or not with enfuvirtide.

Results of the Apollo study

The analysis included 194 participating patients (100 in the ‘intensification’ group and 94 in the ‘standard’ group).

The majority of patients were male, with an average age of 44, and were in an advanced stage of the disease, with severe immunodeficiency and high HIV viremia. 81% of patients received lopinavir/ritonavir and 19% received efavirenz (antiretroviral drug chosen by the investigator).

At week 24, 34% of patients in the ‘intensification’ group and 38% of those in the ‘standard’ group had CD4 counts ≥200/mm3 (primary endpoint, p=0.53). The proportions of patients with plasma HIV-1 RNA <50 copies/ml were 74% and 58% at week 24, respectively (p<0.02). At week 48, 79% of patients had viraemia <50 copies/ml in both groups.

The conclusion of the Apollo study is that the addition of enfuvirtide to standard triple therapy in patients with severe immunodeficiency and high HIV viral replication did not induce a higher CD4 immune response at 48 weeks. Nevertheless, the decline in viraemia was faster in the group receiving intensified treatment. The treatments were generally well tolerated with expected side effects, and discontinuation of enfuvirtide was most often due to difficulties in using this drug.

For more details, see the fact sheets available at the bottom of this page.

Secondary objectives

The secondary objectives of the Apollo study were to compare the two groups (with or without enfuvirtide intensification) at week 24 and week 48:

• clinical progression of HIV-1 infection;
• frequency of immune restoration syndrome;
• the frequency of adverse events related or unrelated to the trial treatments;
• changes in CD4+ T cells (CD4) and plasma HIV-1 RNA;
• resistance mutations (reverse transcriptase, protease, envelope) appearing in the event of virological failure;
• changes in trial treatments;
• changes in HIV-1 proviral DNA;
• changes in hepatitis B virus DNA between S0 and S48 in patients carrying HbsAg;
• adherence and quality of life.

Publications

• Intensification of antiretroviral therapy through addition of enfuvirtide in naive HIV-1-infected patients with severe immunosuppression does not improve immunological response: results of a randomized multicenter trial (ANRS 130 Apollo).  Joly V, Fagard C, Grondin C, Descamps D, Yazdanpanah Y, Charpentier C, Colin de Verdiere N, Tabuteau S, Raffi F, Cabie A, Chene G, Yeni P; S 130 Apollo Trial Group. Antimicrob Agents Chemother. 2013 Feb;57(2):758-65. doi: 10.1128/AAC.01662-12. Epub 2012 Nov 19
• Role and evolution of viral tropism in patients with advanced HIV disease receiving intensified initial regimen in the ANRS 130 APOLLO trial.  Charpentier C, Joly V, Larrouy L, Fagard C, Visseaux B, de Verdière NC, Raffi F, Yeni P, Descamps D; ANRS 130 APOLLO Trial Study Group. J Antimicrob Chemother. 2013 Mar;68(3):690-6. doi: 10.1093/jac/dks455. Epub 2012 Nov 14