Acne Treatment for HIV

Minocycline is a derivative of the tetracycline class of antibiotics that works by shutting down protein synthesis in susceptible bacteria. The drug can be used to treat acne, anthrax, and various other bacterially derived diseases. Interestingly, a new study published in The Journal of Infectious Diseases suggests that minocycline can also be used to combat HIV.

The authors used a version of HIV that expresses green fluorescent protein (GFP) in place of an HIV encoded structural gene to infect activated T-cells in the presence or absence of minocycline. When minocycline was present, so too were a lower number of cells expressing GFP, suggesting the drug may curb HIV infection. This effect was also dose dependent, as the number of cells expressing GFP decreased as the minocycline dose increased

To further characterize minocyclines contribution to curbing HIV infection, the authors measured HIV DNA and RNA levels in activated and infected T-cells. Minocycline lowered RNA levels but not DNA levels. This suggests that minocycline does not alter viral entry or reverse transcription of the RNA HIV genome, but inhibits replication and viral production. T-cell activation is required for HIV RNA production and the authors observed that minocycline treatment mimicked a state in which infected T-cells were inactivated. In other words, the authors postulated that minocycline may block a T-cell activation process that is required for HIV replication.

To test their hypothesis, the authors used T-cells in a latent state that were infected with HIV and assessed whether minocycline could alter HIV after activating the T-cells. Using a GFP reporter as before, the authors observed less HIV activity in minocycline pretreated cells. Integrated HIV DNA was present in these T-cells, but minocycline prevented its response to T-cell activation signals as postulated.

Next the authors used T-cells from actual HIV infected patients to determine if minocycline could inhibit HIV replication in a more physiological scenario. Resting T-cells from HIV patients were stimulated and HIV RNA levels were measured. Consistent with the previous experiments, minocycline inhibited replication of the virus as measured by HIV RNA production.

This study suggests that the antibiotic minocycline may have a therapeutic role in suppressing HIV replication. Interestingly, the mechanism by which minocycline inhibits HIV activity is by suppressing T-cell activity. The authors suggest that minocycline may be used as a maintenance therapy for HIV infection. However, inhibiting T-cells further in HIV patients may actually be counter productive unless a pool of uninfected T-cells can be developed by the patient that can ultimately hold off opportunistic pathogens. Furthermore, long term treatment with antibiotics can lead to the emergence of resistant bacteria and change the normal flora of the patient, leaving them susceptible to infection. Although promising, further research is needed to understand the potential place of minocycline in HIV therapy.

References:

Szeto, GL., et, al. Minocycline Attenuates HIV Infection and Reactivation by Suppressing Cellular Activation in Human CD4+ T Cells. J Infect Dis. 2010 Apr 15;201(8):1132-4.