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Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers.

Hatano H, Yukl SA, Ferre AL, Graf EH, Somsouk M, Sinclair E, Abdel-Mohsen M, Liegler T, Harvill K, Hoh R, Palmer S, Bacchetti P, Hunt PW, Martin JN, McCune JM, Tracy RP, Busch MP, O'Doherty U, Shacklett BL, Wong JK, Deeks SG - PLoS Pathog. (2013)

Bottom Line: Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART.Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART.Similar reductions were observed in the subset of "elite" controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL).

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.

ABSTRACT
The study of HIV-infected "controllers" who are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy (ART) may provide insights for HIV cure and vaccine strategies. Despite maintaining very low levels of plasma viremia, controllers have elevated immune activation and accelerated atherosclerosis. However, the degree to which low-level replication contributes to these phenomena is not known. Sixteen asymptomatic controllers were prospectively treated with ART for 24 weeks. Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART. Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART. Similar reductions were observed in the subset of "elite" controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL). These data confirm that HIV replication persists in controllers and contributes to a chronic inflammatory state. ART should be considered for these individuals (ClinicalTrials.gov NCT01025427).

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Related in: MedlinePlus

Change in high sensitivity C-reactive protein.Thin lines indicate data for each individual subject. The thick line indicates the estimated mean value over time from mixed effects linear regression. P-values refer to change from baseline at each referenced time-point. hsCRP = high sensitivity C-reactive protein.
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ppat-1003691-g007: Change in high sensitivity C-reactive protein.Thin lines indicate data for each individual subject. The thick line indicates the estimated mean value over time from mixed effects linear regression. P-values refer to change from baseline at each referenced time-point. hsCRP = high sensitivity C-reactive protein.

Mentions: At baseline, the median (IQR) levels of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), soluble CD14 (sCD14), and D-dimer were 1.20 (0.55, 3.03) ug/mL, 1.71 (1.28, 4.42) pg/mL, 1696 (1446, 1971) ng/mL, and 0.37 (0.28, 0.56) ug/mL, respectively. After ART initiation, there was a trend towards a decrease in hsCRP, with a mean 1.74-fold decrease (95% CI 3.2-fold decrease to 1.04-fold increase, p = 0.069) at week 4, and a mean 1.67-fold decrease (95% CI 3.0-fold decrease to 1.09-fold increase, p = 0.093) at week 24 (Fig. 7). We also observed similar trends in IL-6 (mean 1.34-fold decrease, 95% CI 2.1-fold decrease to 1.19-fold increase, p = 0.22), sCD14 (mean −44.2, 95% CI −138.6 to +50.3, p = 0.36), and D-dimer (mean 1.30-fold decrease, 95% CI 2.1-fold decrease to 1.25-fold increase, p = 0.29) levels after 24 weeks of ART, although these trends did not reach statistical significance.


Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers.

Hatano H, Yukl SA, Ferre AL, Graf EH, Somsouk M, Sinclair E, Abdel-Mohsen M, Liegler T, Harvill K, Hoh R, Palmer S, Bacchetti P, Hunt PW, Martin JN, McCune JM, Tracy RP, Busch MP, O'Doherty U, Shacklett BL, Wong JK, Deeks SG - PLoS Pathog. (2013)

Change in high sensitivity C-reactive protein.Thin lines indicate data for each individual subject. The thick line indicates the estimated mean value over time from mixed effects linear regression. P-values refer to change from baseline at each referenced time-point. hsCRP = high sensitivity C-reactive protein.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3795031&req=5

ppat-1003691-g007: Change in high sensitivity C-reactive protein.Thin lines indicate data for each individual subject. The thick line indicates the estimated mean value over time from mixed effects linear regression. P-values refer to change from baseline at each referenced time-point. hsCRP = high sensitivity C-reactive protein.
Mentions: At baseline, the median (IQR) levels of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), soluble CD14 (sCD14), and D-dimer were 1.20 (0.55, 3.03) ug/mL, 1.71 (1.28, 4.42) pg/mL, 1696 (1446, 1971) ng/mL, and 0.37 (0.28, 0.56) ug/mL, respectively. After ART initiation, there was a trend towards a decrease in hsCRP, with a mean 1.74-fold decrease (95% CI 3.2-fold decrease to 1.04-fold increase, p = 0.069) at week 4, and a mean 1.67-fold decrease (95% CI 3.0-fold decrease to 1.09-fold increase, p = 0.093) at week 24 (Fig. 7). We also observed similar trends in IL-6 (mean 1.34-fold decrease, 95% CI 2.1-fold decrease to 1.19-fold increase, p = 0.22), sCD14 (mean −44.2, 95% CI −138.6 to +50.3, p = 0.36), and D-dimer (mean 1.30-fold decrease, 95% CI 2.1-fold decrease to 1.25-fold increase, p = 0.29) levels after 24 weeks of ART, although these trends did not reach statistical significance.

Bottom Line: Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART.Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART.Similar reductions were observed in the subset of "elite" controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL).

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.

ABSTRACT
The study of HIV-infected "controllers" who are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy (ART) may provide insights for HIV cure and vaccine strategies. Despite maintaining very low levels of plasma viremia, controllers have elevated immune activation and accelerated atherosclerosis. However, the degree to which low-level replication contributes to these phenomena is not known. Sixteen asymptomatic controllers were prospectively treated with ART for 24 weeks. Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART. Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART. Similar reductions were observed in the subset of "elite" controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL). These data confirm that HIV replication persists in controllers and contributes to a chronic inflammatory state. ART should be considered for these individuals (ClinicalTrials.gov NCT01025427).

Show MeSH
Related in: MedlinePlus