Medical UV Exposures and HIV Activation

Abstract

This paper presents the first attempt to evaluate the potential of clinical UV exposures to induce the human immunodeficiency (HIV) promoter and, thus, to upregulate HIV growth in those skin cells that are directly affected by the exposure. Using the data for HIV promoter activation in vitro, we computed UVB and psoralen plus UVA (PUVA) doses that produce 50% of the maximal promoter activation (AD50). Then, using (a) literature data for UV transmittance in the human skin, (b) a composite action spectrum for HIV promoter and pyrimidine dimer induction by UVB and (c) an action spectrum for DNA synthesis inhibition by PUVA, we estimated the distribution of medical UVB and PUVA doses in the skin. This allowed us to estimate how deep into the skin the HIV-activating doses might penetrate in an initial and an advanced stage of UVB or PUVA therapy. Such analysis was done for normal type II skin and for single exposures. The results allow us to predict where in the skin the HIV promoter may be induced by selected small and large therapeutic UVB or PUVA doses. To accommodate changes in skin topography due to disease and UV therapy, our considerations would require further refinements. For UVB we found that, when the incident dose on the surface of the skin is 500 J/m2 (290-320 nm) (initial stage of the therapy), the dose producing 50% of the maximal HIV promoter activation (ADUVB50) is limited to the stratum corneum. However, with an incident dose of 5000 J/m2 (an advanced stage of the therapy), ADUVB50) may be delivered as far as the living cells of the epidermis and even to some parts of the upper dermis. For PUVA we found that, when the incident UVA doses are 25 or 100 kJ/m2 (320-400 nm) (an initial and an advanced stage of therapy, respectively), and the 8-methoxypsoralen concentration in the blood is 0.1 microgram/mL (the desired level), the combined doses to the mid epidermis (and some areas of the upper dermis) are well below the 50% HIV promoter-activating PUVA dose (ADPUVA50). Only under the worst scenario conditions, i.e. an exceptionally high drug concentration in the patient's tissues and localization of HIV in the nearest proximity to the skin surface, would the combined PUVA dose expected during photochemotherapy exceed ADPUVA50. These results suggest that the probability of HIV activation in the epidermis by direct mechanisms is higher for UVB than for PUVA treatment. However, complexities of the UV-inducible HIV activation and immunomodulatory phenomena are such that our results by themselves should not be taken as an indication that UVB therapy carries a higher risk than PUVA therapy when administered to HIV-infected patients.

UVB and PUVA therapies in HIV patients: are they safe?

“…We assumed that HIV activation is a DNA-damage-dependent process and took into consideration the spectral absorption of UVA and UVB radiation in the skin. The results suggest that a therapeutic UVB exposure is more effective than PUVA exposure as an activating agent for HIV in the skin (9). Thus, at least from the viewpoint of HIV activation, PUVA may not be more hazardous than UVB.…”

HIV‐Associated Eosinophilic Pustular Folliculitis: Successful Treatment of a Japanese Patient with UVB Phototherapy

“…The abstract for the study by Duvic et al (34) includes no documentation of the dose. More recently, the investigation by Zmudzka et al (35) revealed that large UVB doses (for example 7 MED) may produce exposure sufficient to activate the HIV promoter in the epidermis but that small doses (below 1 MED) carry no risk of activation when the normalized MED value is used for type II skin. We conducted the UVB phototherapy in our patient with the dose at the end-point still below 1 MED and with a cumulative dose of 2,320 mJ/cm 2 , which provided adequate clinical effect without unfavorable side effects.…”

“…Some authors consider further investigation and observation required before any definite conclusion is drawn concerning the safety of UVB phototherapy in HIV-infected patients (35,36). Nevertheless, at present, UVB phototherapy is very attractive for patients with the HIV-associated form because of its rapid and profound effect on the intense pruritus of the lesions, which is a source of distress to the patients.…”

Ultraviolet Therapy and Patients With HIV Infection

“…As a result, there is little information on the relative safety of these 2 therapies when used for patients with HIV. It would be highly desirable to expand our knowledge of the safety of PUVA therapy for HIV infection, since there is good reason to expect that it might be at least as safe as UV-B therapy 3 and, perhaps, more effective. 16 Studies on the use of PUVA comparable to the UV-B study reported by Gelfand et al,13 See also page 940 EDITORIAL as well as the studies on PUVA-induced HIV load and immune changes in the skin, would put the 2 alternative therapies on an even footing.…”