Human immunodeficiency virus (HIV) infection and related immunosuppression are associated with excess risk for cervical neoplasia and human papillomavirus (HPV) persistence. Type-specific HPV infection was assessed at 6-month intervals for HIV-positive and HIV-negative women (median follow-up, 2.5 and 2.9 years, respectively). The type-specific incidence of HPV infection was determined, and risk factors for HPV persistence were investigated by statistical methods that accounted for repeated measurements. HIV-positive women were 1.8, 2.1, and 2.7 times more likely to have high-, intermediate-, and low-risk HPV infections, respectively, compared with HIV-negative women. In multivariate analysis, high viral signal, but not viral risk category, was independently associated with persistence among HIV-positive subjects (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-2.9). Furthermore, persistence was 1.9 (95% CI, 1.5-2.3) times greater if the subject had a CD4 cell count <200 cells/microL (vs. >500 cells/microL). Thus, HIV infection and immunosuppression play an important role in modulating the natural history of HPV infection.
HAART altered the course of HPV disease in HIV-infected women, reducing progression and increasing regression. As HPV disease is a common sex-specific manifestation of HIV disease this effect of HAART would be a major additional benefit from this modality of therapy.
Increased risk for cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HIV)-infected women may be explained by repeated positivity of human papillomavirus (HPV) infection facilitated by HIV infection and related immunosuppression. As part of a longitudinal study with semiannual examinations, 268 women in Baltimore, Maryland (of whom 184 were HIV+), provided 1,426 cervicovaginal lavage specimens tested for HPV DNA by a polymerase chain reaction-based assay between 1992 and 1998. HPV positivity and time to HPV clearance according to HIV serostatus and CD4+ cell count were compared using models for correlated binary data and survival analysis. Of the 187 participants who had at least one positive measurement, the probability of subsequent HPV positivity among HIV- women and HIV+ women with CD4+ > or =200 and <200 cells/microl was 47.5%, 78.7%, and 92.9% (p < 0.001). Within-women HPV results were correlated (i.e., clustered) in each group (p < 0.01). Compared with HIV-participants, the relative incidence of HPV clearance was 0.29 and 0.10 among HIV+ women with CD4+ > or =200 and <200 cells/microl (p < 0.001). At the end of follow-up, 11 women had biopsy-confirmed CIN. The association of HIV and CIN (p = 0.014) was fully explained by repeated HPV positivity induced by HIV infection (p = 0.648). Reversal of immunosuppression following potent antiretroviral therapy must be expected to have a dramatic impact on HIV-related CIN.
Although HIV infected women were at high risk for abnormal cytology, high-grade changes were uncommon. HIV status, HPV detection, CD4 lymphocyte count, and HIV RNA level predicted the incidence of cervical cytologic abnormalities. Progression was significantly increased only among the most immunosuppressed women, while regression was significantly reduced in all HIV seropositive women except those with the best controlled HIV disease.
To characterize selection factors related to therapy initiation, the authors investigated the extent to which key markers of human immunodeficiency virus (HIV) disease severity were associated with initiation of potent antiretroviral therapy (ART). Logistic regression was used to determine the effects of CD4+ cell count and HIV RNA level on potent ART initiation during 6-month periods among 2,059 HIV-infected US women enrolled in the Women's Interagency HIV Study. Low CD4+ counts and high HIV RNA levels were significantly (p < 0.05) associated with initiation of potent ART. During all periods between April 1996 and March 1998, CD4+ counts were more strongly associated with potent ART initiation than HIV RNA levels were; however, during the last period, both were associated (odds ratio per 100 CD4+-count decrease = 1.17, p < 0.01; odds ratio per 1 log10 increase in HIV RNA level = 1.48, p < 0.05). For a CD4+ count of 500 cells/ml and an HIV RNA level of 5,000 copies/ml, the probability of potent ART initiation increased from 0.5% to 16.8% between October 1995-March 1996 and October 1997-March 1998, suggesting earlier initiation of potent ART. Given the documented occurrence of confounding by indication, prospectively collected, time-dependent data on markers of disease progression and therapy use should be considered when making population-level comparisons before and after introduction of potent ART.
To improve our assessment of differences in health status among racial, ethnic, and national origin groups, research involving these categories should assess their validity and should define concepts clearly, explicitly, and consistently. Such research would minimize misclassification, improve the interpretation of findings, facilitate comparison among studies, and enhance the understanding of causes underlying differences in health status among populations of different racial, ethnic, and national origins.
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