The human immunodeficiency virus (HIV), identified in 1983, is a lentivirus, a member of the retrovirus family. HIV is responsible for the acquired immunodeficiency syndrome (AIDS), a condition in which progressive weakening of the immune system allows lifethreatening opportunistic infections to thrive in humans. Although HIV is preventable through effective public health measures, substantial HIV transmission continues worldwide. To date, 1.7 million newly infected HIV individuals have been reported. In particular, about 142,000 newly diagnosed HIV infections were reported in 50 of the 53 countries in the European Region of the World Health Organization (WHO), 3,000 of which were reported in Italy. In the last decade, an increase of HIV-1 non-B subtypes and circulating recombinant forms (CRFs) have been reported in several European countries, including Italy, commonly attributed to the increased proportion of migrants from non-European countries. In fact, only in Italy, migrants accounted for nearly 30% of all newly diagnosed HIV infections in recent years. Moreover, a considerable proportion of the new diagnoses still involves people with high-risk sexual behaviors such as men who have sex with men (MSM), despite the increasing use of pre-exposure prophylaxis (PrEP). Most of the studies have focused on HIV transmission among chronically infected subjects, but the spread of HIV-1 is largely driven by individuals who have recently acquired the infection. Because a good portion of the new diagnoses involves well-defined clusters prevalently characterised by high-risk sexual behaviours, accurate identification of these transmission clusters and an understanding of HIV transmission dynamics are very important to efficiently target public health interventions. To design better tailored public health HIV control and prevention initiatives, a more accurate understanding of HIV transmission dynamics is needed. In relation to this, molecular surveillance for HIV plays an important role as it is commonly based on the phylogenetic analysis of pol sequences obtained in the context of antiretroviral resistance diagnosis. Phylogenetic analysis represents one of the most important strategies to better describe and monitor the local HIV epidemics by correlating genetic relationship of the viruses with information on nationality, transmission route, the newly infected, drug resistance, viro-immunological parameters, and year of infection. In this regard, the overall aim of this thesis was to evaluate HIV-1 transmission in drugnaïve individuals in Italy. In particular, HIV-1 molecular transmission clusters (MTCs) were characterized in three distinct populations: i) individuals infected with non-B subtypes; ii) native and foreign individuals living in Italy; iii) individuals diagnosed with primary HIV-1 infection (PHI). Potential demographic and viro-immunological differences between patients in MTCs and those out of MTCs were evaluated for each population.
Il virus dell'immunodeficienza umana (HIV), identificato nel 1983, è un lentivirus, un membro della famiglia dei retrovirus. L'HIV è responsabile della sindrome da immunodeficienza acquisita (AIDS), una condizione in cui il progressivo indebolimento del sistema immunitario consente alle infezioni opportunistiche potenzialmente letali di prosperare negli esseri umani. Sebbene l’infezione da HIV sia prevenibile attraverso efficaci misure di sanità pubblica, essa continua a rappresentare un grave problema a livello mondiale. Ad oggi, sono stati segnalati 1,7 milioni di persone con infezione da HIV. In particolare, sono state segnalate circa 142,000 nuove diagnosi da HIV in 50 dei 53 paesi della Regione Europea dell'Organizzazione Mondiale della Sanità (OMS), mentre sono stati segnalati circa 3,000 nuovi casi in Italia. Nell'ultimo decennio, un aumento dei sottotipi non-B di HIV-1 e delle forme ricombinanti circolanti (CRF) è stato segnalato in diversi paesi europei, inclusa l'Italia. Questo aumento viene comunemente attribuito all'aumento della proporzione di immigrati provenienti da paesi non europei. In Italia, i migranti rappresentano quasi il 30% di tutte le infezioni da HIV di nuova diagnosi negli ultimi anni. Inoltre, una parte considerevole delle nuove diagnosi coinvolge ancora persone con comportamenti sessuali ad alto rischio come per esempio gli individui omosessuali, nonostante il crescente utilizzo della profilassi preesposizione (PrEP). La maggior parte degli studi si è concentrata sulla trasmissione dell'HIV tra soggetti con infezione cronica, ma la diffusione dell'infezione da HIV è in gran parte guidata da individui che hanno recentemente contratto l'infezione e che sono quindi in infezione acuta. Una parte considerevole delle nuove diagnosi è coinvolta in cluster ben definiti caratterizzati prevalentemente da comportamenti sessuali ad alto rischio. L'identificazione accurata di questi cluster di trasmissione e la comprensione delle dinamiche di trasmissione dell'HIV sono molto importanti per indirizzare in modo efficiente gli interventi di sanità pubblica. Per progettare iniziative di prevenzione e controllo dell'HIV per la sanità pubblica più personalizzate, è necessaria una comprensione più accurata delle dinamiche di trasmissione dell'HIV. A questo proposito, la sorveglianza molecolare gioca un ruolo importante. La sorveglianza molecolare per l'HIV è comunemente basata sull'analisi filogenetica delle sequenze pol, ottenuta nel contesto della diagnosi del test genotipico di resistenza antiretrovirale. In particolare, l'analisi filogenetica rappresenta una delle strategie più importanti per descrivere e monitorare meglio le epidemie locali di HIV, correlando la composizione genetica del virus con le informazioni su nazionalità, via di trasmissione, nuove infezioni, farmacoresistenza, parametri viro-immunologici, e anno di infezione. A tal proposito, l'obiettivo generale di questa tesi è stato quello di valutare la trasmissione dell'HIV-1 in individui naïve ai farmaci antiretrovirali in Italia. In particolare, i cluster molecolari di trasmissione (MTC) dell'HIV-1 sono stati caratterizzati in tre popolazioni distinte: i) individui infetti con sottotipi non-B; ii) individui nativi e stranieri che vivono in Italia; iii) individui con diagnosi di infezione primaria da HIV-1. Per ciascuna popolazione sono state valutate le potenziali differenze demografiche e viroimmunologiche tra i pazienti negli MTC e quelli fuori dagli MTC.
Evaluation of Hiv-1 molecular transmission clusters among drugnaïve individuals in Italy
FABENI, LAVINIA
2021
Abstract
The human immunodeficiency virus (HIV), identified in 1983, is a lentivirus, a member of the retrovirus family. HIV is responsible for the acquired immunodeficiency syndrome (AIDS), a condition in which progressive weakening of the immune system allows lifethreatening opportunistic infections to thrive in humans. Although HIV is preventable through effective public health measures, substantial HIV transmission continues worldwide. To date, 1.7 million newly infected HIV individuals have been reported. In particular, about 142,000 newly diagnosed HIV infections were reported in 50 of the 53 countries in the European Region of the World Health Organization (WHO), 3,000 of which were reported in Italy. In the last decade, an increase of HIV-1 non-B subtypes and circulating recombinant forms (CRFs) have been reported in several European countries, including Italy, commonly attributed to the increased proportion of migrants from non-European countries. In fact, only in Italy, migrants accounted for nearly 30% of all newly diagnosed HIV infections in recent years. Moreover, a considerable proportion of the new diagnoses still involves people with high-risk sexual behaviors such as men who have sex with men (MSM), despite the increasing use of pre-exposure prophylaxis (PrEP). Most of the studies have focused on HIV transmission among chronically infected subjects, but the spread of HIV-1 is largely driven by individuals who have recently acquired the infection. Because a good portion of the new diagnoses involves well-defined clusters prevalently characterised by high-risk sexual behaviours, accurate identification of these transmission clusters and an understanding of HIV transmission dynamics are very important to efficiently target public health interventions. To design better tailored public health HIV control and prevention initiatives, a more accurate understanding of HIV transmission dynamics is needed. In relation to this, molecular surveillance for HIV plays an important role as it is commonly based on the phylogenetic analysis of pol sequences obtained in the context of antiretroviral resistance diagnosis. Phylogenetic analysis represents one of the most important strategies to better describe and monitor the local HIV epidemics by correlating genetic relationship of the viruses with information on nationality, transmission route, the newly infected, drug resistance, viro-immunological parameters, and year of infection. In this regard, the overall aim of this thesis was to evaluate HIV-1 transmission in drugnaïve individuals in Italy. In particular, HIV-1 molecular transmission clusters (MTCs) were characterized in three distinct populations: i) individuals infected with non-B subtypes; ii) native and foreign individuals living in Italy; iii) individuals diagnosed with primary HIV-1 infection (PHI). Potential demographic and viro-immunological differences between patients in MTCs and those out of MTCs were evaluated for each population.File | Dimensione | Formato | |
---|---|---|---|
Fabeni Lavinia__PhDThesis.pdf
accesso solo da BNCF e BNCR
Dimensione
3.89 MB
Formato
Adobe PDF
|
3.89 MB | Adobe PDF |
I documenti in UNITESI sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/20.500.14242/208907
URN:NBN:IT:UNIROMA2-208907