Association of HIV Viral Load and CD4 Cell Count With HPV
Association of HIV Viral Load and CD4 Cell Count With HPV
Objectives The extent to which highly active antiretroviral therapy (HAART) affects human papillomavirus (HPV) acquisition and clearance in HIV-infected women is not well understood. We sought to describe high-risk HPV detection and clearance rates over time since HAART initiation, based on time-varying HIV viral load (VL) and CD4 T-cell count, using novel statistical methods.
Methods We conducted a retrospective analysis of data from the completed AIDS Clinical Trials Group (ACTG) A5029 study using multi-state Markov models. Two sets of high-risk HPV types from 2003 and 2009 publications were considered.
Results There was some evidence that VL > 400 HIV-1 RNA copies/mL was marginally associated with a higher rate of HPV detection [P = 0.068; hazard ratio (HR) = 4.67], using the older set of high-risk HPV types. Such an association was not identified using the latest set of HPV types (P = 0.343; HR = 2.64). CD4 count >350 cells/μL was significantly associated with more rapid HPV clearance with both sets of HPV types (P = 0.001, HR = 3.93; P = 0.018, HR = 2.65). There was no evidence that HPV affects VL or CD4 cell count in any of the analyses.
Conclusions High-risk HPV types vary among studies and can affect the results of analyses. Use of HAART to improve CD4 cell count may have an impact on the control of HPV infection. The decrease in VL may also have an effect, although to a lesser degree.
Immunosuppression is associated with the prevalence and persistence of human papillomavirus (HPV), but the extent to which highly active antiretroviral therapy (HAART) affects HPV acquisition and clearance in HIV-infected women is not well understood. A number of studies have shown that HPV infection and cervical dysplasia risks are elevated among women who are infected with HIV and immunosuppressed, but mixed results have been obtained with regard to the effect of HAART on the progression of HPV infection. Classification of high-risk HPV types associated with cervical cancer varies among studies, as knowledge has evolved over time, and this may contribute to the mixed results in the literature. Also, data from HPV studies can be difficult to analyse because of infrequent testing for HPV detection (every 6–12 months); small numbers of visits (over 3–5 years); and unknown rates and durations of transient HPV infections. For instance, HPV detection at two study visits 12 months apart may indicate a persistent infection or an infection that cleared and recurred between the visits.
To address the limitations of the data, a statistical approach using multi-state models was applied to describe HPV detection and clearance events that may be recurrent. We conducted a retrospective analysis on AIDS Clinical Trials Group (ACTG) A5029 data to describe and compare HPV detection and clearance rates with time-varying HIV viral load (VL) and CD4 cell count in HIV-infected women initiating HAART, when the exact times of HPV status changes are unavailable. Two sets of high-risk HPV types from 2003 and 2009 publications were considered to evaluate the sensitivity of the analysis to evolving HPV types thought to be oncogenic.
Abstract and Introduction
Abstract
Objectives The extent to which highly active antiretroviral therapy (HAART) affects human papillomavirus (HPV) acquisition and clearance in HIV-infected women is not well understood. We sought to describe high-risk HPV detection and clearance rates over time since HAART initiation, based on time-varying HIV viral load (VL) and CD4 T-cell count, using novel statistical methods.
Methods We conducted a retrospective analysis of data from the completed AIDS Clinical Trials Group (ACTG) A5029 study using multi-state Markov models. Two sets of high-risk HPV types from 2003 and 2009 publications were considered.
Results There was some evidence that VL > 400 HIV-1 RNA copies/mL was marginally associated with a higher rate of HPV detection [P = 0.068; hazard ratio (HR) = 4.67], using the older set of high-risk HPV types. Such an association was not identified using the latest set of HPV types (P = 0.343; HR = 2.64). CD4 count >350 cells/μL was significantly associated with more rapid HPV clearance with both sets of HPV types (P = 0.001, HR = 3.93; P = 0.018, HR = 2.65). There was no evidence that HPV affects VL or CD4 cell count in any of the analyses.
Conclusions High-risk HPV types vary among studies and can affect the results of analyses. Use of HAART to improve CD4 cell count may have an impact on the control of HPV infection. The decrease in VL may also have an effect, although to a lesser degree.
Introduction
Immunosuppression is associated with the prevalence and persistence of human papillomavirus (HPV), but the extent to which highly active antiretroviral therapy (HAART) affects HPV acquisition and clearance in HIV-infected women is not well understood. A number of studies have shown that HPV infection and cervical dysplasia risks are elevated among women who are infected with HIV and immunosuppressed, but mixed results have been obtained with regard to the effect of HAART on the progression of HPV infection. Classification of high-risk HPV types associated with cervical cancer varies among studies, as knowledge has evolved over time, and this may contribute to the mixed results in the literature. Also, data from HPV studies can be difficult to analyse because of infrequent testing for HPV detection (every 6–12 months); small numbers of visits (over 3–5 years); and unknown rates and durations of transient HPV infections. For instance, HPV detection at two study visits 12 months apart may indicate a persistent infection or an infection that cleared and recurred between the visits.
To address the limitations of the data, a statistical approach using multi-state models was applied to describe HPV detection and clearance events that may be recurrent. We conducted a retrospective analysis on AIDS Clinical Trials Group (ACTG) A5029 data to describe and compare HPV detection and clearance rates with time-varying HIV viral load (VL) and CD4 cell count in HIV-infected women initiating HAART, when the exact times of HPV status changes are unavailable. Two sets of high-risk HPV types from 2003 and 2009 publications were considered to evaluate the sensitivity of the analysis to evolving HPV types thought to be oncogenic.
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