6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 25–28 October 2004 - Washington, DC, USA

LOSS OF WEIGHT IN THE ERA OF HAART IS ASSOCIATED WITH ELEVATED PBMC PROVIRAL DNA LEVELS

Antiviral Therapy 2004; 9(6):L35 (abstract no. 57)

CM Shikuma, V Valcour, S Ratto-Kim, AE Williams, S Souza, M Gerschenson, JH Kim and B Shiramizu
Hawaii AIDS Clinical Research Program, John A Burns School of Medicine, University of Hawaii - Manoa, Honolulu, HI, USA

OBJECTIVE: Loss of weight continues to be seen in HIV⁺ subjects in developed countries despite widespread availability of potent antiretroviral therapy. Catabolic cytokines such as TNF-α are often elevated in these subjects. Residual HIV infection in cells of the monocyte/macrophage (M/MΦ) lineage have been demonstrated in antiretroviral-treated HIV-infected individuals with undetectable plasma HIV-1 RNA by PCR. We hypothesize that weight loss in the era of HAART may be secondary to residual HIV infection in (M/MΦ) with resultant increases in catabolic cytokine production and release.

METHODS: PBMC proviral DNA copies/cell (assessed by real-time PCR), select plasma cytokine levels (assessed by ELISA) and weight records over the first year of follow-up were available and analysed in a subset of 67 HIV⁺ subjects participating in the Hawaii Aging with HIV longitudinal cohort study.

RESULTS: 17.0% had weight loss >10%, 14.9% had weight loss from >5% to 10%, 61.7% maintained stable weight with less than 5% gain or loss, and 6.4% demonstrated weight gain. PBMC proviral DNA levels were higher in those with weight loss >5% compared with those with stable or increasing weight (median 8.9 vs 0.9 copies/10⁶ cells; P=0.006 by Mann–Whitney). Proviral DNA levels remained higher in the 52% of subjects with plasma HIV RNA levels <50 copies/ml (median 8.9 vs 0.5 copies/10⁶ cells, P=0.028 Mann–Whitney). Analysis in selected specimens to ascertain HIV DNA in subsets of PBMCs demonstrated that the majority of proviral DNA copies in PBMCs were in activated (CD14⁺/CD16⁺ by flow) macrophages. A correlation was demonstrated between proviral DNA levels and sTNFRII levels (r=0.72, P=0.043) (n=8).

CONCLUSIONS: Weight loss in the era of HAART may be driven by residual HIV infection in cells of the monocyte/macrophage lineage.

Acknowledgement: Supported by NIH/NINDS U54 NS4 3049.

2004-10-25
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