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

Abstract

Strategies to cure HIV-infected patients by virus-targeting drugs have failed to date. We identified a HIV-1-seropositive woman who spontaneously suppressed HIV replication and had normal CD4-cell counts, no HIV disease, no replication-competent virus and no cell HIV DNA detected with a routine assay. We suspected that dramatic HIV DNA degradation occurred postinfection. We performed multiple nested-PCRs followed by Sanger sequencing and applied a multiplex-PCR approach. Furthermore, we implemented a new technique based on two hybridization steps on beads prior to next-generation sequencing that removed human DNA then retrieved integrated HIV sequences with HIV-specific probes. We assembled ≈45% of the HIV genome and further analyzed the G-to-A mutations putatively generated by cellular APOBEC3 enzymes that can change tryptophan codons into stop codons. We found more G-to-A mutations in the HIV DNA from the woman than in that of her contaminator. Moreover, 74% of the tryptophan codons were changed to stop codons (25%) or were deleted as a possible consequence of gene inactivation. Finally, we found that this woman’s cells remained HIV-susceptible in vitro. Our findings show that she does not exhibit innate HIV resistance but has been cured of it by extrinsic factors, a plausible candidate for which is the gut microbiota.

Genomic description and prevalence of two new Candidatus Saccharibacteria species from the human gut in different samples and countries

“…Furthermore, following a thorough metagenomic analysis, we found a signi cant proportion of Candidatus M.massiliensis (7,024 reads with a relative abundance of 0.9%) in a fecal metagenome from a patient who had spontaneously been cured of HIV infection 25 . We were able to cover only 88% of the genome by mapping the Candidatus M.massiliensis genome and we detected a second novel genome of Candidatus Saccharibacteria species that we named Candidatus M.timonensis.…”

“…A specimen was collected preceding the fecal microbiota transplantation. In parallel, the second subject was a 39-year-old woman who was spontaneously cured of HIV 25 . Unlike the previous faecal sample, this one was obtained directly from the stool.…”