Background:  While initiation of HAART during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in viremia. Here we report a patient who presented with severe meningo-encephalitis and was started on HAART during primary infection when his viral load was >750,000 copies/mL and Western blot testing was indeterminate. This patient continues to maintain viral loads of <50 copies/mL more than 9 years after the cessation of treatment.

Methods:  Viral isolates from primary infection and year 11 post-infection were cultured from plasma and CD4⁺ T cells, respectively. Whole genome sequence analysis and fitness assays were performed on isolates from both time points. Viral tropism was determined with a phenotypic assay using GHOST cells expressing CCR5 and/or CCXR4. Neutralization antibody assays were performed with recombinant virus expressing either autologous or heterologous env. CD8⁺ T cell responses to epitopes in gag and nef genes were analyzed using the IFN-γ ELISpot assay, and the ability of HIV-specific cytotoxic T lymphocytes (CTL) to inhibit viral replication was determined in a suppression assay. 

Results:  This patient had a relatively high frequency of latently infected CD4⁺ T cells compared to patients who spontaneously maintain undetectable viral loads (elite suppressors). Viral isolates from primary infection and year 11 were all CCR5/CXCR4 dual-tropic and fully replication-competent in vitro. A comparison of isolates from primary infection and year 11 revealed minimal viral evolution. The patient does not have any known protective HLA alleles or genetic factors, and his CD4⁺ T cells are fully susceptible to infection. He currently has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates, and his CD8⁺ T cells do not have potent HIV suppressive activity.

Conclusions:  This case represents the longest viral control after treatment cessation to our knowledge. The mechanism of control of viral replication is unknown, but it is unlikely that the patient was destined to become a natural elite suppressor. This case suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent CTL-mediated suppression that has been reported in many elite suppressors.