Hydroxychloroquine fails to modify HIV in patients not taking ART

By MedWire Reporters

The use of hydroxychloroquine does not reduce CD8 cell activation in HIV-infected patients not taking antiretroviral therapy (ART), research shows.

Use of hydroxychloroquine did accelerate the decline in CD4 cell count and increased viral replication.

The unexpected findings demonstrate that hydroxychloroquine "is not of benefit in modifying HIV disease course in patients with high CD4 cell counts who have not yet started antiretroviral therapy," report Nicholas Paton (Medical Research Council Clinical Trials Unit, London, UK) and colleagues.

In an editorial accompanying the study, James Stein (University of Wisconsin, Madison, USA) and Priscilla Hsue (University of California, San Francisco, USA) state that, despite the negative results, the findings "do not exclude the possibility that hydroxychloroquine or other immunomodulators could reduce immune activation and inflammation in virologically suppressed patients receiving ART."

Published in the Journal of the American Medical Association, the study included 83 patients with asymptomatic HIV infection who were not taking ART and who had CD4 cell counts greater 400 cells/µL.

The researchers treated the patients with hydroxychloroquine, a drug with immunomodulatory and anti-inflammatory properties that has been used for many years in the treatment of T-cell-mediated immune diseases such as lupus. It interferes with T-cell activation and has been shown to have in vivo and in vitro anti-HIV properties.

In this placebo-controlled trial, patients were randomized to hydroxychloroquine 400 mg or placebo for 48 weeks.

CD8 cell activation declined by 4.8% in the hydroxychloroquine group and by 4.2% in the placebo group, a nonsignificant between-group difference.

Declines in CD4 cell count were significantly greater in the hydroxychloroquine‑treated patients compared with the placebo‑treated patients (-85 cells/µL versus -23 cells/µL).

In addition, viral load increased significantly compared with the placebo-treated patients and more patients treated with hydroxychloroquine had to initiate ART (nine patients versus one in the placebo arm).

"Contrary to our original hypothesis, we found that hydroxychloroquine accelerated the decline in CD4 cell count and shortened the time to starting antiretroviral therapy," write Paton and colleagues.

They suggest that alternative interventions are needed to reduce immune activation and disease progression in early HIV infection. Like the editorialists, they suggest the use of hydroxychloroquine still needs to be tested in patients taking ART.

"Given the potential for complex and unpredictable effects, interventions for immune activation must be evaluated rigorously in adequately powered randomized controlled trials," they conclude.

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  1. Michael Davis, M.D. Michael Davis, M.D. United States says:

    The findings in the above reference contradict findings reported for this agent in many studies dating back to 1990.  Figure 2 in that study shows CD4 decline for the placebo and hydroxychloroquine (HQ) groups. At the viral loads that were treated, the HQ group more closely approximates natural progression of the untreated patient at a CD4 decline rate of 50-75 cells/mm3/year.(1,2) The viral load was slightly higher in the HQ group, but CD4 decline in the placebo group was less than reports of expected rates of decline in untreated individuals. My perception is that the group labeled placebo benefitted from therapy while the group labeled HQ followed the natural course of the untreated.    The ranges in that graph also show that some in the placebo group had an increase in CD4 levels.  CD4 levels at 4 weeks are shown in Fig 2 while the text states that CD4 levels and viral load were not tested at the 4 week visit.

    1. Differences in HIV Natural Historyamong African and Non-African Seroconverters in Europe and Seroconverteres in Sub-Saharan Africa. PLosOne.org March 2012 Vol(7) Issue 3. e32369

    2.  Predictive Value of Plasma HIV RNA Level on Rate of CD4 T-cell decline in untreated HIV infection.  JAMA Sept 27, 2006, Vol 296 (12) 1498-1506

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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