Flushing out HIV

Another proposed strategy is to ‘flush’ HIV out of latently infected cells. The persistence of latently infected cells is widely assumed to be the major barrier to curing HIV infection. Scientists are still working on identifying all cell types and body tissues in which HIV might remain latent. Since HIV can only replicate in activated cells, ‘waking up’ inactive cells could force it to produce new virus particles that are susceptible to current antiretroviral drugs. This "shock and kill" approach could also pose serious risks should the immune system become overly disrupted.

Several methods have been tried to stimulate inactive cells infected with HIV. Some studies have shown that the immune system chemical messenger interleukin-7 (IL-7) and a protein kinase activator called prostratin can trigger resting CD4 T-cells to produce HIV without stimulating activation of all T-cells.^1,2 Further information on cytokine therapy can be found in the section Cytokine therapy (IL-2 and IL-7).

Valproic acid (Depakote / Convulex), a drug used to treat epilepsy and bipolar disorder, also inhibits the activity of the enzyme histone deacetylase 1 (HDAC1), which is involved in the packaging of DNA within cells. While one small proof-of-concept study showed that adding valproic acid to ART reduced the number of resting HIV-infected cells in treated patients,³ this was not borne out by two subsequent studies which found no effect on the size of the HIV reservoir.^{4 5 6}

Other types of HDAC inhibitors, the so-called class I HDACs, have been found to awaken some latently HIV-infected cells, which then died out while uninfected cells remained unaffected.They found that at non-toxic quantities, class I HDAC inhibitors could cause some of the latently infected cells to awaken. More (but still not all) latently infected cells were affected when class I HDAC inhibitors were combined with buthionine sulfoximine (BSO) to reduce cellular glutathione levels. Glutathione creates oxidative stress within the cells that contributes to viral transcription. As HIV replication and BSO deplete cellular glutathione, the cell is moved toward a state in which it is more likely to self-destruct, thus removing the virus-producing cell from the reservoir.²

While these results are promising, the researchers point out that there are different cellular reservoirs for HIV-1 latency and each may require a targeted approach. Additionally, HDAC inhibitors might not control other possible viral factors related to latency.