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

Background We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. Methods Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection 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. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. Results Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805–1336), and normal CD4/CD8 ratio (median 1.8, range 1.2–1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4–14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). Conclusions Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation

Summary of clinical parameters at each visit.

<p>Summary of clinical parameters at each visit.</p

Baseline demographics of the patients treated with methylprednisolone.

<p>Baseline demographics of the patients treated with methylprednisolone.</p

Effect of methyl prednisolone on gait.

<p>A, Change in 10m timed walk as the median of the percentage difference (%) in comparison to D0. B, Correlation between the 10m TW (seconds) at D0 and an improvement in the 10m TW from D0 to D2 (seconds) using Pearson’s correlation coefficient of the sample (r). Outliers were excluded. C, Correlation between duration of disease and improvement in 10m TW. Scatter plot with line of best fit showing duration of disease (months) against the improvement in the 10m TW (seconds) at D2 using Pearson’s correlation coefficient of the sample (r). Outliers were excluded.</p

Summary of cytokine concentration in response to pulsed IV methylprednisolone.

<p>Summary of cytokine concentration in response to pulsed IV methylprednisolone.</p

Correlations between cytokines, pain and gait.

<p>Pearson correlation coefficient of the sample (r) was used to assess the correlation between reductions in TNF-α and IL-6 concentration (pg/ml) with improvements in the 10m TW (seconds) and pain (VAS) from D0 to D2. <b>A)</b> Correlation between TNF-α concentration and pain. <b>B</b>) Correlation between TNF-α concentration and 10m TW. <b>C</b>) Correlation between IL-6 concentration and pain. <b>D</b>) Correlation between IL-6 concentration and 10m TW.</p