Functional cure of HIV-1 infection in an exceptional elite controller: a case report

Identifying characteristics associated with functional cure of HIV-1 infection is of pivotal importance. Here, we describe a unique case of functional cure in an exceptional elite controller, comparing immunological, virological, and clinical characteristics with those of other elite controllers.

In this case report, we compared the case (a heterosexual Indian woman aged 48 years) with her partner (an Indian man aged 58 years) and a cohort of elite controllers (people with HIV with at least three consecutive plasma HIV viral loads below detection during at least 12 months of follow-up, in the absence of antiretroviral therapy; cohort 1) and long-term elite controllers (elite controllers with immunological [no statistically significant decrease of CD4 cell count] and virological control during a minimum of 10 years and maintained at follow-up; cohort 2), from reference hospitals in Madrid, Spain. A group of HIV-negative donors was also included. The case was first diagnosed with sexually transmitted HIV-1 infection in 2002, after her partner was diagnosed with HIV-1 infection and Pneumocystis jiroveci pneumonia. We did a comprehensive analysis of virological and host features. Virological assays were reservoir quantification, quantitative viral outgrowth assay, and next-generation sequencing of viral RNA and DNA; host assays were HLA-I typing, host restriction factors, plasma inflammatory markers, HIV-1 specific T-cell response, and immunophenotypic analysis of T cells, monocytes, and natural killer cells.

The case maintained undetectable plasma viral load and stable CD4 cell count in the absence of combination antiretroviral therapy for 22 years and never presented clinical manifestations or symptoms related to HIV infection. Western blot reactivity was limited to glycoprotein 41 and glycoprotein 160. HIV-1 DNA was undetectable in resting memory CD4 cells and peripheral T follicular helper cells. Full-length individual proviral sequencing assays revealed only 0·82 HIV genomes per million CD4 cells; all were defective with large internal deletions. Replication-competent viruses were not detected. Compared with reference cohorts 1 (n=9) and 2 (n=12), the case had increased expression of several microRNAs and mRNAs with anti-HIV action; preservation of T-cell homoeostasis with low expression of markers of cell exhaustion (PD1, Tim3, CTLA4, and TIGIT), apoptosis (CD28 and CD95), and senescence (CD28 and CD57); natural killer cells with low inhibitory receptor expression and higher expression of regulatory natural killer cells; and decreased plasma expression of several inflammatory markers (D-dimer, TNFR1, and VCAM-1).

Functional cure is an uncommon but feasible outcome of HIV-1 infection. Our findings encourage the search for therapeutic strategies that could enable people with HIV-1 to reach this level of functional cure.

Carlos III Institute of Health (Spain).