Long-term outcome of dolutegravir-containing regimens according to sex: data from the ICONA study
Authors: D’arminio Monforte Antonella , Tavelli Alessandro , Sala Matteo , Mondi Annalisa , Rusconi Stefano , Antinori Spinello , Puoti Massimo , Celesia Benedetto Maurizio , Taramasso Lucia , Saracino Annalisa , Antinori Andrea , Cozzi-Lepri Alessandro ,   ICONA Foundation Study Group, d’Arminio Monforte A , Antinori A , Antinori S , Castagna A , Castelli F , Cauda R , Di Perri G , Girardi E , Iardino R , Lazzarin A , Marchetti G C , Mussini C , Sarmati L , von Schloesser F , Viale P , d’Arminio Monforte A , Antinori A , Castagna A , Ceccherini-Silberstein F , Cingolani A , Cozzi-Lepri A , Girardi E , Gori A , Lo Caputo S , Marchetti G , Maggiolo F , Mussini C , Puoti M , Perno C F , Agrati C , Antinori A , Bai F , Bandera A , Bonora S , Calcagno A , Cannetti D , Castagna A , Ceccherini-Silberstein F , Cervo A , Cicalini S , Cingolani A , Cinque P , Cozzi-Lepri A , d’Arminio Monforte A , Di Biagio A , Gagliardini R , Giacomelli A , Girardi E , Gianotti N , Gori A , Guaraldi G , Lanini S , Lapadula G , Lichtner M , Lai A , Lo Caputo S , Madeddu G , Maggiolo F , Malagnino V , Marchetti G , Mussini C , Nozza S , Perno C F , Piconi S , Pinnetti C , Puoti M , Quiros Roldan E , Rossotti R , Rusconi S , Santoro M M , Saracino A , Sarmati L , Spagnuolo V , Squillace N , Svicher V , Taramasso L , Vergori A , Bovis F , Cozzi-Lepri A , Fanti I , Ponzano M , Rodano’ A , Tavelli A , Bove A , Cernuschi M , Cosmaro L , Errico M , Perziano A , Calvino V , Carrara S , Graziano S , Prota G , Truffa S , Vincenti D , D’Errico Y , Giacometti A , Costantini A , Barocci V , Saracino A , Santoro C , Milano E , Maggiolo F , Suardi C , Viale P , Badia L , Cretella L , Quiros Roldan E , Focà E , Minardi C , Menzaghi B , Abeli C , Chessa L , Pes F , Maggi P , Alessio L , Cacopardo B , Celesia B , Vecchiet J , Falasca K , Pan A , Dal Zoppo S , Segala D , Vichi F , Di Pietro M A , Santantonio T , Ferrara S , Bassetti M , Pontali E , Alessandrini A , Bobbio N , Mazzarello G , Lichtner M , Fondaco L , Piconi S , Molteni C , Chiodera A , Milini P , Nunnari G , Pellicanò G , d’Arminio Monforte A , Antinori S , Lazzarin A , Rizzardini G , Puoti M , Gori A , Castagna A , Bandera A , Bono V , Cossu M V , Giacomelli A , Lolatto R , Moioli M C , Pezzati L , Tincati C , Mussini C , Puzzolante C , Bonfanti P , Lapadula G , Sangiovanni V , Gentile I , Esposito V , Fusco F M , Di Filippo G , Rizzo V , Sangiovanni N , Cattelan A M , Marinello S , Cascio A , Colomba C , Francisci D , Schiaroli E , Parruti G , Sozio F , Blanc P , Vivarelli A , Lazzaretti C , Corsini R , Andreoni M , Antinori A , Cauda R , Mastroianni C , Cingolani A , Mazzotta V , Lamonica S , Capozzi M , Mondi A , Rivano Capparuccia M , Iaiani G , Stingone C , Gianserra L , Paulicelli J , Plazzi M M , d’Ettore G , Fusto M , Cecchetto M , Viviani F , Madeddu G , De Vito A , Fabbiani M , Montagnani F , Franco A , Fontana Del Vecchio R , Pasticci BM , Di Giuli C , Orofino GC , Calleri G , Di Perri G , Bonora S , Accardo G , Tascini C , Londero A , Manfrin V , Battagin G , Starnini G , Ialungo A 
Published: February 2023

Objectives

To compare the long-term risk of treatment failure of dolutegravir-based ART in men and women in a real-life setting.

Patients and methods

Persons living with HIV (PLWH) from the ICONA cohort were included if they had started dolutegravir in a two- or three-drug regimen as ART-naive or as virologically controlled ART-experienced. The primary endpoint was time to treatment failure (virological/clinical failure or dolutegravir discontinuation). Secondary endpoints were: time to dolutegravir discontinuation due to toxicity and to neuropsychiatric adverse events; and time to virological failure. Cox regression analyses focused on differences in outcomes by sex.

Results

A total of 2304 PLWH (15% women) initiated dolutegravir-based therapy from ART-naive, and 1916 (19.8% women) while experienced. After a median follow-up of 2.2 (IQR: 0.9–3.9) years in ART-naive and 2.4 (IQR: 1.1–4.3) years in experienced, the 4-year cumulative probability of treatment failure was 33% (95% CI 30.5–35.1) and 20% (95% CI 17.8–22.3), respectively. In the multivariable analyses, in ART-naive the risk of treatment failure was higher for women, but not different after excluding women discontinuing dolutegravir for pregnancy concerns. We also observed a higher risk of discontinuation for toxicity in women (ART-naives: Adjusted Hazard Ratio (AHR): 1.56%; 95% CI: 1.03–2.37; ART-experienced: AHR: 1.53%; 95% CI: 1.01–2.32), although the absolute 4-year probability was low: 7.7% (95% CI 6.5–9.2) in ART-naive and 8.3% (95% CI 6.9–9.9) in experienced.

Conclusions

In our cohort of PLWH treated with dolutegravir-based regimens and followed up for up to 4 years, we observed a low risk of treatment failure and no evidence for a difference by sex, after excluding discontinuation due to pregnancy concerns. However, we observed a higher risk of dolutegravir discontinuation for toxicity in women.