Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study

Abstract

Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

“…Adult case series from prospective observational cohort studies and the results of the Agence Nationale de Recherche sur le SIDA (ANRS) Virological and Immunological Studies in Controllers after Treatment Interruption (VISCONTI) study suggest that some patients with different genetic characteristics and characteristic CD8 cell response to HIV, after prolonged treatment of primary HIV infection, can control HIV replication post treatment interruption for at least several years 211, 212. It appears that restricting the pool of HIV‐infected cells by very early treatment might decrease long‐lived viral reservoirs 213, which may be essential for successful control without therapy 212.…”

Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure?

“…Indeed, PTCs had more severe primary infections than did HICs (figure 2 HIV remission It is likely that infection control in PTCs was not achieved spontaneously but was favoured by the early initiation of therapy. The frequency of PTCs is estimated at between 5% and 15% of patients beginning cART shortly after primary HIV infection [17][18][19][20], which is significantly higher than the proportion of HICs [21,22]. Such a significant proportion of PTCs has been observed only after early initiation of treatment and not when therapies were begun during the chronic phase, in which reported cases are even scarcer [23].…”

Quels enjeux de recherche trente ans après l’identification du virus VIH ?

“…Ces réservoirs expliquent la résurgence très rapide de la virémie chez la majorité des patients dès que la prise d'antirétroviraux est interrompue. Or, une étude française publiée en mars 2013, décrit les cas de 14 patients positifs pour le VIH traités très précocement après la primo-infection et qui, plus de sept ans après l'arrêt des antirétroviraux, contrôlent leur infection (cohorte ANRS EP47 VIS-CONTI) [8]. Après la description, début mars 2013, d'un état de rémission fonctionnelle chez un bébé aux États-Unis, et au vu des données de la cohorte ANRS Primo [9], ces résultats confirment, sur un nombre plus grand de patients et sur une période plus étendue, le rôle déterminant d'une intervention thérapeutique précoce pour induire un contrôle fonctionnel de l'infection VIH.…”