To the Editors:
Patients coinfected with HIV have a greater likelihood of human papilloma virus (HPV) persistence and extensive and unremitting anogenital wart disease.1–3 Anogenital-related HPV immune reconstitution–associated disease has previously been reported, but it is not widely recognized.4,5 Our aim was to assess CD4+ T-lymphocyte counts at the time of anogenital warts diagnosis and to characterize the therapeutic management and the recurrence rate of anogenital warts in patients coinfected with HIV.
Using a tertiary referral hospital database, 298 patients with anogenital warts seen in our sexually transmitted disease consultations, between January 2005 and December 2009, were identified. Data from a minimum 18 months follow-up period were available. Demographics, clinical, laboratorial, and therapeutic management data were obtained from clinical record reviews and analyzed. The statistical significance of the results was calculated using SPSS v17 statistical software (SPSS Inc; Chicago, IL).
We identified 62 patients coinfected with HIV (20.8%) with ages ranging from 17 to 73 years (mean: 38.3 years; SD ± 10.2 years) and mainly men (80.7%). This group had median CD4+ T-lymphocyte counts of 371 cells per cubic millimeter at the first consultation for genital warts (18% had CD4 counts <200 cells/mm3, 51% had CD4 counts of 200–499 cells/mm3, 18% had CD4 counts >500 cells/mm3, and the remaining data were not available). In 4 patients, the consultation for warts allowed the diagnosis of a hitherto unknown HIV infection (mean CD4 counts of 657 cells/mm3). Forty-four patients were on highly active antiretroviral treatment (HAART), among whom 47.7% of patients had a coincident recovery in the immunity at the time of anogenital warts diagnosis. This group of patients last mentioned had an average increase of CD4+ T-lymphocyte count of 162 cells per cubic millimeter with a median time to onset of warts of 13 weeks; the mean CD4 counts before initiating HAART was 380 cells per cubic millimeter (minimum 7; maximum 936), and the mean CD4 counts at the time of anogenital warts diagnosis was 541 cells per cubic millimeter (minimum 276; maximum 1330).
The most used treatment in HIV patients was liquid nitrogen cryotherapy, in 53 patients (86.0%), and in average each patient had 3 treatment sessions. Twenty-six (41.9%) patients were treated with 20% topical podophyllin resin solution, 11 (17.7%) were treated with 80% trichloroacetic acid, imiquimod 5% cream was used in 8 patients (12.9%), and surgical excision was done in 2 (3.2%) patients. The frequency distribution of treatment procedures was similar to the seronegative population. The recurrence rate of anogenital warts in HIV patients was 12.9% (8/62) and occurred in average after 9.9 months, compared with 9.3% (22/236) in the HIV-seronegative patients (P = 0.476), after 8.3 months in average. At the time of recurrence, HIV patients had mean CD4 counts of 580 cells per cubic millimeter.
It is worth emphasizing that the development of anogenital warts in our HIV patients was associated with moderate stages of immunosupression. Interestingly also, in almost half of the patients under HAART, it seemed to be related to immune reconstitution, with anogenital warts evolving during the course of an increase of CD4 counts due to effective treatment for HIV. Cutaneous immune reconstitution–associated disorders have been reported by some authors, although its pathogenesis is incompletely understood.4,5 In the HAART era, HPV-induced diseases present a challenging problem. With the widespread use of HAART, on the contrary to the expected, the incidence of HPV-induced diseases did not decrease.6 Probably because HIV patients under HAART fail to reconstitute the specific immunity against HPV, which requires both an increase of CD4+ T lymphocyte and also reinfection and reexposure to sufficient amounts of HPV-derived antigens under an inflammatory environment.7
The current available treatment methods for anogenital warts are unspecific, and our data, though not statistically significant, corroborate previous findings that show a trend for anogenital warts to recur at a higher frequency in HIV patients.8 Clearly, future research studies to identify the ideal therapeutic option for anogenital warts in patients coinfected with HIV are required. As the current nonspecific treatment options available are not satisfactory, we must look at prevention. The role of prophylactic vaccines against HPV (quadrivalent, against HPV types 6, 11, 16, and 18) must be considered.9,10 Safe, well-tolerated, and effective preventing anogenital warts in individuals who were not infected at baseline, the vaccine is also beneficial preventing anogenital cancer induced by HPV 16 and HPV 18 in vulnerable sexually active patients, especially within the highest risk population, the men who have sex with men.10 Recent reports showed that the quadrivalent vaccine is also highly immunogenic in HIV patients.9 These patients would greatly benefit from prophylactic HPV immunization, and doing that we can protect those who are still susceptible to the HPV types of the vaccine.9 This is an important tool to further explore in HIV patients while we wait for the HPV-specific therapeutic vaccination that is under development.7
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