Prevalence of acquired resistance mutations in a large cohort of perinatally infected HIV-1 patients

Ungaro, Ryan C.; Taramasso, Lucia; Vicenti, Ilaria; Borghi, Vanni; Callegaro, Annapaola; Giacometti, Andrea; Butini, Luca; Gobbo, R. Del; Bagnarelli, Patrizia; Tacconi, Danilo; Corbelli, Giovanni; Zanussi, Stefania; Monno, Laura; Punzi, Grazia; Maggiolo, Franco; Calza, Leonardo; Re, Maria Carla; Pristerà, Raffaele; Turconi, Paola; Mandas, Antonella; Tini, Sauro; Zoncada, Alessia; Paolini, Elisabetta; Amadio, Giorgio; Sighinolfi, Laura; Corsi, Paola; Galli, Luisa; Pietro, Massimo Di; Colao, G; Tosti, Andrea; Setti, Maurizio; Bruzzone, Bianca; Biagio, Antonio Di; Cenderello, Giovanni; Trezzi, Michele; Orani, Anna Maria; I, Arcidiacono; Degiuli, Alberto; Gennaro, Michele De; Chiodera, Alessandro; Scalzini, Alfredo; Palvarini, Loredana; Todaro, Giovanni; Rusconi, Stefano; Gismondo, Maria Rita; Micheli, Valeria; Biondi, Maria Luisa; Capetti, Amedeo; Meraviglia, Paola; Boeri, Enzo; Mussini, Cristina; Pecorari, Monica; Soria, Alessandro; Vecchi, L.; Santirocchi, Maurizio; Brustia, Diego; Ravanini, Paolo; Bello, Federico Dal; Romano, Nino; Mancuso, Salvatrice; Calzetti, C; Maserati, Renato; Filice, G.; Baldanti, Fausto; Francisci, Daniela; Parruti, Giustino; Polilli, Ennio; Sacchini, D.; Martinelli, Chiara; Consolini, Rita; Vatteroni, L; Vivarelli, Angela; Nerli, A; Lenzi, Lucia; Magnani, Giacomo; Ortolani, Patrizia; Andreoni, Massimo; Fimiani, Caterina; Palmisano, Lucia; Giambenedetto, Simona Di; Vullo, Vincenzo; Turriziani, Ombretta; Montano, Marco Aurélio Echart; Antinori, Andrea; Zaccarelli, Mauro; Dentone, Chiara; Gonnelli, A.; Luca, Andrea De; Palumbo, Marco; Ghisetti, Valeria; Bonora, Stefano; Foglie, P. Delle; Rossi, Cristina; Mondino, Vincenzo; Malena, Marina; Grossi, Paolo; Seminari, Elena; Poletti, Federica

doi:10.1016/j.cmi.2019.07.004

Cited by 11 publications

(7 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of children who died or developed HIV-related clinical events presented detectable viral loads. This finding suggests that there is probably a serious problem with adherence to therapy and considerable efforts still need to be made in order to implement strategies to improve the adherence itself (57). Our data shows that we cannot yet consider HIV infection completely harmless.…”

Section: Discussionmentioning

confidence: 83%

Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background: Combined antiretroviral therapy (cART) has been associated with a steep decrease in mortality and morbidity in HIV-1 infected children. New antiretroviral molecules and drug classes have been developed and the management of HIV-infected children has improved, but recent data on survival are limited.Methods: An observational retrospective study investigating changes in mortality and morbidity was conducted on 1,091 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018.Results: Three hundred and fifty-four (32%) AIDS events and 26 (2%) deaths occurred overtime. Mortality rates decreased from 0.4/100 person-years in 2001–2006 to 0.27/100 person-years in 2007–2012 and 0.07/100 person-years in 2013–2018. Notably, 92% of the dead children were born in Italy, but only 50% were followed-up since birth or within three months of age. Seventy three percent of children had started cART at age ≥6 months; 23% were treated for <30 days before death. B and C clinical events progressively decreased (P < 0.0001). Opportunistic infections significantly decreased over time, but still were the most common events in all the periods (6.76/100 person-years in 2013–2018). In the last period, severe bacterial infections were the most common ones. Cancer rates were 0.07/100; 0.17/100; 0.07/100 person-years in the three periods, respectively.Conclusions: Progressive reductions both in mortality and in rates of class B and C clinical events and OIs have been observed during the cART era. However, deaths were still registered; more than half of dead children were enrolled after birth and had belatedly started cART.

show abstract

Section: Discussionmentioning

confidence: 83%

Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In perinatally HIV-infected children (PHIV) born to infected mothers, early ART shapes the HIV reservoir and the immune response ( 30 – 32 ). PHIV patients who were born in the early 90s and are now adolescents or young adults did not have the opportunity for early ART and were sometimes exposed to months or years of suboptimal antiretroviral regimens prior to combined antiretroviral therapy (cART) ( 33 , 34 ). In this context, viremia copy years (VCY), a metric of cumulative HIV RNA burden calculated based on longitudinal viral load data, has been used to summarize in a single value the viral burden of years ( 35 , 36 ).…”

Section: Introductionmentioning

confidence: 99%

Persistence of Unintegrated HIV DNA Associates With Ongoing NK Cell Activation and CD34+DNAM-1brightCXCR4+ Precursor Turnover in Vertically Infected Patients Despite Successful Antiretroviral Treatment

et al. 2022

Self Cite

View full text Add to dashboard Cite

The quantification of proviral DNA is raising interest in view of clinical management and functional HIV eradication. Measures of all unintegrated HIV DNA (uDNA) forms in infected reservoir cells provides information on recent replication events that is not found from other proviral DNA assays. To evaluate its actual relevance in a cohort of perinatally-infected adult HIV patients (PHIV), we studied how peripheral blood mononuclear cell uDNA levels correlated with total HIV DNA (tDNA) and with overall replication or innate immune control parameters including NK cell activation/exhaustion and lymphoid turnover. Twenty-two PHIV were included, with successfully controlled HIV (HIV RNA <50 copies/mL) on combined antiretroviral therapy for mean of 8.7 ± 3.9 years. uDNA accounted for 16 [5.2-83.5] copies/µg and was strongly correlated with tDNA (ρ=0.700, p=0.001). Flow cytometric analysis of peripheral NK cells showed that CD69 expression was directly correlated uDNA (p=0.0412), but not with tDNA. Interestingly, CD56-CD16+NK cells which include newly described inflammatory precursors and terminally differentiated cells were directly correlated with uDNA levels (p<0.001), but not with tDNA, and an inverse association was observed between the proportion of NKG2D+ NK cells and uDNA (ρ=-0.548, p=0.015). In addition, CD34+DNAM-1brightCXCR4+ inflammatory precursor frequency correlated directly with uDNA levels (ρ=0.579, p=0.0075). The frequencies of CD56-CD16+ and CD34+DNAM-1brightCXCR4+ cells maintained association with uDNA levels in a multivariable analysis (p=0.045 and p=0.168, respectively). Thus, control of HIV-1 reservoir in aviremic patients on ART is an active process associated with continuous NK cell intervention and turnover, even after many years of treatment. Quantification of linear and circular uDNA provides relevant information on the requirement for ongoing innate immune control in addition to ART, on recent replication history and may help stratify patients for functional HIV eradication protocols with targeted options.

show abstract

“…What we do know is that overall in the patients included, although they were young, the average number of regimens of antiretroviral therapy taken was 5.6, with a maximum recorded number of 24 regimens; this finding is in‐line with that reported by a recent Italian study of the ARCA cohort on the prevalence of resistance‐associated genotypic mutations in adults with vertical HIV infection, which reported a mean number of regimens received of 5. 28 …”

Section: Discussionmentioning

confidence: 99%

Reduced probability of improving viro‐immunological state in subjects with vertical transmission of HIV reaching adult age: A multicenter retrospective cohort study

Pennati

Calza

Biagio

et al. 2023

Immunity Inflam & Disease

Self Cite

View full text Add to dashboard Cite

Introduction Young adults with vertical transmission (VT) of human immunodeficiency virus (HIV) represent a fragile population. This study evaluates factors associated with viro‐immunological outcome of these patients. Methods We performed a multicenter study including HIV‐infected subjects with VT ≥ 18 years old from six Italian clinics. Subjects were observed from birth to death, lost to follow‐up, or last visit until December 31, 2019. Condition of “optimal viro‐immunological status” (OS) was defined as the simultaneous presence of HIV ribonucleic acid (RNA) < 50 copies/mL, CD4+ > 500 cells/mm 3 , and CD4+/CD8+ ratio ≥ 1. Results A total of 126 subjects were enrolled. At 18 years of age, 52/126 (44.4%) had HIV‐RNA > 50 copies/mL, 47/126 (38.2%) had CD4+ < 500/mm 3 , and 78/126 (67.2%) had CD4+/CD8+ < 1; 28 subjects (23.7%) presented in the condition of OS. Having a CD4+/CD8+ ratio ≥ 1 at 18 years of age was related with an increased probability of shift from suboptimal viro‐immunological status (SOS) to OS (HR: 7.7, 95% confidence interval [CI]: 4.23–14.04), and a reduced risk of shift from the OS to the SOS (HR: 0.49, 95% CI: 0.26–0.92). Acquired immunodeficiency syndrome (AIDS) diagnosis significantly reduced the probability of shift from a viro‐immunological SOS to OS (HR: 0.09, 95% CI: 0.03–0.30). Subjects who had not achieved an OS at 18 years of age had an increased risk of discontinuation of combination antiretroviral therapy (cART, p = .019). Conclusions Only a small proportion of subjects with VT of HIV reached the adult age with “OS”. Transition to the adult care with a compromised viro‐immunological condition represents a negative driver for future optimal infection control, with a higher risk of discontinuation of cART and a reduced probability to improve the immunological status later in the years.

show abstract

Prevalence of acquired resistance mutations in a large cohort of perinatally infected HIV-1 patients

Cited by 11 publications

References 8 publications

Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018

Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018

Persistence of Unintegrated HIV DNA Associates With Ongoing NK Cell Activation and CD34+DNAM-1brightCXCR4+ Precursor Turnover in Vertically Infected Patients Despite Successful Antiretroviral Treatment

Reduced probability of improving viro‐immunological state in subjects with vertical transmission of HIV reaching adult age: A multicenter retrospective cohort study

Contact Info

Product

Resources

About