Reevaluation of possible outcomes of infections with human immunodeficiency virus

Abstract

Several lines of evidence indicate that HIV infection can result in several possible incomes, including a very small proportion of individuals whose HIV replication is controlled after treatment interruption (known as HIV posttreatment controllers) or spontaneously without any treatment (known as HIV elite controllers). Both types of individuals are HIV RNA negative but HIV DNA positive, with living virus which can be stimulated ex vivo. A review was conducted to assess the literature on yet rarer cases with detectable integrated HIV DNA without HIV infectious virus in HIV-seropositive or -negative individuals. Three categories of patients were identified: (a) HIV-seropositive individuals with apparent spontaneous cure from their HIV infection, (b) HIV-seronegative children born to HIV-infected mothers and (c) highly exposed seronegative adults. Validity criteria were proposed to assess the presence of integrated HIV DNA as possible or unquestionable in these three categories. Only three articles among the 22 ultimately selected fulfilled these criteria. Among the highly exposed seronegative subjects, some individuals were described as being without integrated HIV DNA, probably because these subjects were not investigated using relevant, highly sensitive methods. Finally, we propose a definition of spontaneous cure of HIV infection based on clinical, immunologic and virologic criteria.

RETRACTED ARTICLE: Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection

“…We previously described two HIV-1-seropositive patients who we believe might have been spontaneously cured of HIV 15,16 . Indeed, although they never received antiretrovirals, they persistently have a suppressed HIV replication, normal CD4 T cell counts, and no HIV-related disease for more than 10 years (one was HIV-diagnosed in 1985).…”

Directed Mutations Recode Mitochondrial Genes: From Regular to Stopless Genetic Codes

“…This was originally interpreted as resulting from directed selection on stop codons. Observations of systematic mutations in contexts creating stop codons in ORFs of HIV genes specifically in elite controllers immune to HIV [73,74] suggests that enzymatically directed mutagenesis during DNA replication and/or edition could transform ORFs coded according to a regular genetic code into one coded by a stopless genetic code, and vice versa, as observed in several mitochondrial genes of the Olive Ridley. For HIV, introducing stops presumably drastically reduces viral production and contributes to immunity.…”

Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection

“…This occurred through G-to-A mutations, which is the signature of APOBEC3 cellular enzymes, and led to gene inactivation by changing tryptophan codons into stop codons. Clinically, the woman never developed immunodeficiency or HIV-related symptoms, which suggests that she was cured of HIV 15 . The fate of HIV infection was totally different in her contaminator although both individuals where infected with a same HIV strain.…”

“…We previously described two HIV-1-seropositive patients who we believe might have spontaneously cured of HIV 14,15 . Indeed, although they never received antiretrovirals, they persistently have a suppressed HIV replication, normal CD4 T cell counts, and no HIV-related disease for more than 10 years (one was HIV-diagnosed in 1985).…”