Characterization of Rare Spontaneous Human Immunodeficiency Virus Viral Controllers Attending a National United Kingdom Clinical Service Using a Combination of Serology and Molecular Diagnostic Assays

Abstract

We report outcomes and novel characterisation of a unique cohort of 42 individuals with persistently indeterminate HIV status, the majority of whom are HIV viral controllers. Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV RNA by commercial assays and were not taking ART. Routine investigations included: HIV Western blot; HIV viral load; qualitative HIV-1 DNA; co-infection screen and T-cell quantification. Research assays included T-cell activation; ART measurement; single copy assays detecting HIV-1 RNA and DNA and plasma cytokine quantification. HIV seropositivity was defined as ≥3 bands on Western blot; molecular positivity as detection of HIV RNA or DNA. HIV infection was excluded in 10/42 referrals, remains unconfirmed in 2/42 and was confirmed in 30/42, who were identified as HIV elite controllers (EC), normal CD4 T-cell counts (median 820/ml, range 805-1336) and normal CD4:CD8 ratio (median 1.8, range 1.2-1.9). ECs had a median duration of elite control of 6 years (IQR=4-14). ART was undetected in all 23 tested. Two distinct categories of EC were identified: molecular-positive (n=20) and molecular-negative (n=10). HIV status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the two molecular categories amongst EC requires further investigation.

Pregnancy Management in HIV Viral Controllers: Twenty Years of Experience

“…These current adult treatment guidelines highlight that for viral controllers, who maintain plasma viral concentrations <50 copies/mL without ART and have normal CD4 counts, in the absence of other co-morbid conditions for which ART use is indicated, the benefits of combination ART remain uncertain and recommend that such cases are referred to the UK national NHS clinical service ( imperial.idris@nhs.net ). All patients referred to this clinical service undergo extensive investigations to further characterise their viral control [ 56 ]. A more rigorous definition is applied to include molecular positive or negative features as assessed by proviral DNA and ultrasensitive viral load assays, whilst the presence of immune activation is also assessed.…”