Medical UV exposures and HIV activation

Area of Science:

• Dermatology
• Virology
• Photobiology

Background:

• Clinical ultraviolet (UV) therapies like UVB and psoralen plus UVA (PUVA) are used for various skin conditions.
• The potential for these therapies to activate the human immunodeficiency virus (HIV) promoter in skin cells remains an important consideration, particularly for HIV-infected individuals.

Purpose of the Study:

• To evaluate the potential of clinical UVB and PUVA exposures to induce the HIV promoter and upregulate HIV replication in skin cells.
• To estimate the penetration depth of HIV-activating UV doses within the skin during different stages of therapy.

Main Methods:

• Calculated 50% maximal promoter activation doses (AD50) for UVB and PUVA using in vitro data.
• Utilized UV transmittance data, action spectra for HIV promoter induction, and DNA synthesis inhibition to model UV dose distribution in skin.
• Estimated the penetration of HIV-activating UV doses in normal type II skin for initial and advanced therapy stages.

Main Results:

• For UVB therapy, initial doses (500 J/m2) activate the HIV promoter only in the stratum corneum, while advanced doses (5000 J/m2) can reach the epidermis and upper dermis.
• For PUVA therapy, even at advanced UVA doses (100 kJ/m2) and desired drug levels, the effective dose in the mid-epidermis and upper dermis remains below the 50% activation threshold (ADPUVA50).
• Under worst-case scenarios (high drug concentration, superficial HIV), PUVA doses might exceed ADPUVA50, but generally, UVB appears to have a higher probability of direct HIV promoter induction in the epidermis.

Conclusions:

• UVB therapy may have a higher potential for direct HIV promoter induction in the epidermis compared to PUVA therapy.
• The findings suggest differential risks but should not be interpreted as definitive evidence of increased UVB therapy risk for HIV patients due to complex immunomodulatory factors.