P33.10
Background: In a bid to determine correlates of HIV protection, a whole blood microarray study revealed that HIV exposed seronegative (HESN) sex workers have a significantly lowered glycolyis rate. This suggested that reduction of cell glycolytic activity may be protective or beneficial against HIV Infection. This phenomenon has been noted among cancer cells, where compounds that lower glycolysis rate have been developed as potential therapeutics against malignant carcinoma. Our observation among HESN suggests that similar to cancer cells, HIV maybe utilizing the glycolytic pathway for its energy needs. We have carried a preliminary in vitro analysis to determine if the glycolytic inhibitors, lonidamine LND and 2 Deoxyglucose (2DG), has an anti-HIV effect. and a potential therapeutic against HIV.
Methods: Viral Reverse Transcriptase (RT) was measured from culture supernatant using RT assay on pretreatment (4 hr drug exposed followed by 2 hr virus infection) and co treatment. Cell cytotoxity on mock infected C8166 cells was done in parallel with RT assay using Trypan blue exclusion test and Vi-cell (Beckmancounter) cell viability analyser. Results obtained were normalized and presented as percentages.
Results: Lonidamine co treatment at 100 μM resulted in more than 76% HIV inhibition while 2-DG concentrations at 5 mM had HIV inhibition percentage above 90% inhibition. Cell toxicity assessment at similar concentrations resulted in 75% reduction in actual cell count with LND co treatment. The 2-DG component maintained a cell proliferation of more than 90%.
Conclusions: Glycolytic inhibitors 2-DG and LND have potential anti-HIV activity. However it suggests a better safety profile of 2-DG at effective inhibitory concentrations.
