Durability of different initial regimens in HIV-infected patients starting antiretroviral therapy with CD4+ counts <200 cells/mm3 and HIV-RNA >5 log10 copies/mL
Authors: Gianotti Nicola , Lorenzini Patrizia , Cozzi-Lepri Alessandro , De Luca Andrea , Madeddu Giordano , Sighinolfi Laura , Pinnetti Carmela , Santoro Carmen , Meraviglia Paola , Mussini Cristina , Antinori Andrea , d'Arminio Monforte Antonella ,   ICONA Foundation Study Group, d’Arminio Monforte A , Andreoni M , Angarano G , Antinori A , Castelli F , Cauda R , Di Perri G , Galli M , Iardino R , Ippolito G , Lazzarin A , Perno C F , von Schloesser F , Viale P , d’Arminio Monforte A , Antinori A , Castagna A , Ceccherini-Silberstein F , Cozzi-Lepri A , Girardi E , Lo Caputo S , Mussini C , Puoti M , Andreoni M , Ammassari A , Antinori A , Balotta C , Bandera A , Bonfanti P , Bonora S , Borderi M , Calcagno A , Calza L , Capobianchi M R , Castagna A , Ceccherini-Silberstein F , Cingolani A , Cinque P , Cozzi-Lepri A , d’Arminio Monforte A , De Luca A , Di Biagio A , Girardi E , Gianotti N , Gori A , Guaraldi G , Lapadula G , Lichtner M , Lo Caputo S , Madeddu G , Maggiolo F , Marchetti G , Marcotullio S , Monno L , Mussini C , Nozza S , Puoti M , Quiros Roldan E , Rossotti R , Rusconi S , Santoro M M , Saracino A , Zaccarelli M , Cozzi-Lepri A , Fanti I , Galli L , Lorenzini P , Rodano A , Shanyinde M , Tavelli A , Carletti F , Carrara S , Di Caro A , Graziano S , Petrone F , Prota G , Quartu S , Truffa S , Giacometti A , Costantini A , Valeriani C , Angarano G , Monno L , Santoro C , Maggiolo F , Suardi C , Viale P , Donati V , Verucchi G , Castelli F , Quiros E , Minardi C , Quirino T , Abeli C , Manconi P E , Piano P , Cacopardo B , Celesia B , Vecchiet J , Falasca K , Sighinolfi L , Segala D , Mazzotta F , Vichi F , Cassola G , Viscoli C , Alessandrini A , Bobbio N , Mazzarello G , Mastroianni C , Belvisi V , Bonfanti P , Caramma I , Chiodera A , Castelli A P , Galli M , Lazzarin A , Rizzardini G , Puoti M , d’Arminio Monforte A , Ridolfo A L , Piolini R , Castagna A , Salpietro S , Carenzi L , Moioli M C , Tincati C , Marchetti G , Mussini C , Puzzolante C , Gori A , Lapadula G , Abrescia N , Chirianni A , Borgia G , Di Martino F , Maddaloni L , Gentile I , Orlando R , Baldelli F , Francisci D , Parruti G , Ursini T , Magnani G , Ursitti M A , Cauda R , Andreoni M , Antinori A , Vullo V , Cristaudo A , Cingolani A , Baldin G , Cicalini S , Gallo L , Nicastri E , Acinapura R , Capozzi M , Libertone R , Savinelli S , Latini A , Cecchetto M , Viviani F , Mura M S , Madeddu G , De Luca A , Rossetti B , Caramello P , Di Perri G , C Orofino G , Bonora S , Sciandra M , Bassetti M , Londero A , Pellizzer G , Manfrin V 
Published: May 2019

Objectives

Our aim was to investigate the durability of different initial regimens in patients starting ART with CD4+ counts <200 cells/mm3 and HIV-RNA >5 log10 copies/mL.

Methods

This was a retrospective study of HIV-infected patients prospectively followed in the ICONA cohort. Those who started ART with boosted protease inhibitors (bPIs), NNRTIs or integrase strand transfer inhibitors (InSTIs), with CD4+ <200 cells/mm3 and HIV-RNA >5 log10 copies/mL, were included. The primary endpoint was treatment failure (TF), a composite endpoint defined as virological failure (VF, first of two consecutive HIV-RNA >50 copies/mL after 6 months of treatment), discontinuation of class of the anchor drug or death. Independent associations were investigated by Poisson regression analysis in a model including age, gender, mode of HIV transmission, CDC stage, HCV and HBV co-infection, pre-treatment HIV-RNA, CD4+ count and CD4+/CD8+ ratio, ongoing opportunistic disease, fibrosis FIB-4 index, estimated glomerular filtration rate, haemoglobin, platelets, neutrophils, calendar year of ART initiation, anchor drug class (treatment group) and nucleos(t)ide backbone.

Results

A total of 1195 patients fulfilled the inclusion criteria: 696 started ART with a bPI, 315 with an InSTI and 184 with an NNRTI. During 2759 person-years of follow up, 642 patients experienced TF. Starting ART with bPIs [adjusted incidence rate ratio (aIRR) (95% CI) 1.62 (1.29–2.03) versus starting with NNRTIs; P < 0.001] and starting ART with InSTIs [aIRR (95% CI) 0.68 (0.48–0.96) versus starting with NNRTIs; P = 0.03] were independently associated with TF.

Conclusions

In patients starting ART with <200 CD4+ cells/mm3 and >5 log10 HIV-RNA copies/mL, the durability of regimens based on InSTIs was longer than that of NNRTI- and bPI-based regimens.