Association of HIV Viral Load and CD4 Cell Count With HPV
Association of HIV Viral Load and CD4 Cell Count With HPV
Studies have shown varying effects of HAART on HPV infection and HPV-related cervical dysplasia. Several studies have shown a higher HPV prevalence in women with a lower CD4 cell count and higher likelihood of clearance of HPV with improved CD4 cell count. Research on the association between HIV VL and HPV detection has been limited. One study showed that HIV VL and CD4 cell count in combination appeared to be associated with HPV detection, with varying effects of HIV RNA level on HPV prevalence and incident detection depending on the CD4 cell count stratum. Higher HIV VL may be associated with HPV detection as a result of a possible virus–virus interaction, or inflammatory responses induced by HIV may interfere with a woman's ability to mount an effective immune response to HPV infection. In vitro studies have shown increased expression of HPV E1 and L1 viral genes in the presence of HIV transactivator of transcription (tat) proteins. Our analysis using an older set of high-risk HPV types suggested that higher VL may be associated with HPV detection and hinted at a role of HIV VL in HPV acquisition. However, such an association was not suggested using the latest set of high-risk HPV types. Hence, our research demonstrates the importance of considering the HPV types used when reviewing the literature. It has been postulated that immune reconstitution associated with HAART may lead to clearance of HPV, as has been the case with other viral or nonviral opportunistic infections, and this is consistent with the results of our analyses, where higher CD4 cell count was associated with a higher probability of HPV clearance.
There are a couple of limitations to our analyses. There was a trend for earlier discontinuation in subjects starting with HPV infection, suggesting possible informative censoring, and the small sample size did not allow the use of models that adjust for covariates such as age, cigarette smoking, HPV type and sexual activity. There are several advantages of the statistical methods that we used. The multi-state modelling approach accommodates multiple and recurrent events using intermittent data. The hazard rates are estimated simultaneously in the model, eliminating the need to subset the data to estimate the HPV detection rate among HPV-negative subjects and separately to estimate clearance among the HPV-positive subjects. Also, while other HPV studies have used the midpoint between visit times as the event time (e.g. the time of HPV detection or clearance) or the time of the visit, the methods we used are appropriate when the exact event times are unknown. The approach utilized the incomplete data efficiently and provided a more comprehensive description of the HPV detection and clearance process.
Discussion
Studies have shown varying effects of HAART on HPV infection and HPV-related cervical dysplasia. Several studies have shown a higher HPV prevalence in women with a lower CD4 cell count and higher likelihood of clearance of HPV with improved CD4 cell count. Research on the association between HIV VL and HPV detection has been limited. One study showed that HIV VL and CD4 cell count in combination appeared to be associated with HPV detection, with varying effects of HIV RNA level on HPV prevalence and incident detection depending on the CD4 cell count stratum. Higher HIV VL may be associated with HPV detection as a result of a possible virus–virus interaction, or inflammatory responses induced by HIV may interfere with a woman's ability to mount an effective immune response to HPV infection. In vitro studies have shown increased expression of HPV E1 and L1 viral genes in the presence of HIV transactivator of transcription (tat) proteins. Our analysis using an older set of high-risk HPV types suggested that higher VL may be associated with HPV detection and hinted at a role of HIV VL in HPV acquisition. However, such an association was not suggested using the latest set of high-risk HPV types. Hence, our research demonstrates the importance of considering the HPV types used when reviewing the literature. It has been postulated that immune reconstitution associated with HAART may lead to clearance of HPV, as has been the case with other viral or nonviral opportunistic infections, and this is consistent with the results of our analyses, where higher CD4 cell count was associated with a higher probability of HPV clearance.
There are a couple of limitations to our analyses. There was a trend for earlier discontinuation in subjects starting with HPV infection, suggesting possible informative censoring, and the small sample size did not allow the use of models that adjust for covariates such as age, cigarette smoking, HPV type and sexual activity. There are several advantages of the statistical methods that we used. The multi-state modelling approach accommodates multiple and recurrent events using intermittent data. The hazard rates are estimated simultaneously in the model, eliminating the need to subset the data to estimate the HPV detection rate among HPV-negative subjects and separately to estimate clearance among the HPV-positive subjects. Also, while other HPV studies have used the midpoint between visit times as the event time (e.g. the time of HPV detection or clearance) or the time of the visit, the methods we used are appropriate when the exact event times are unknown. The approach utilized the incomplete data efficiently and provided a more comprehensive description of the HPV detection and clearance process.
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