Frequent Detection of HPV before and after Initiation of Antiretroviral Therapy among HIV/HSV-2 Co-Infected Women in Uganda

<div><h3>Objectives</h3><p>Most data on HPV and antiretroviral therapy (ART) come from high-resource countries with infrequent sampling for HPV pre- and post-ART initiation. Therefore, we examined the frequency of cervical HPV DNA detection among HIV/HSV-2 co-infected women followed monthly for 6 months both before and after initiation of ART in Rakai, Uganda.</p> <h3>Methods</h3><p>Linear Array was used to detect 37 HPV genotypes in self-collected cervicovaginal swabs from 96 women who initiated ART. Random-effects log-binomial regression was used to compare the prevalence of HPV detection in the pre- and post-ART periods and determine other potential risk factors, including CD4 counts and HIV viral load.</p> <h3>Results</h3><p>Nearly all women had detectable HPV in the 6 months preceding ART initiation (92%) and the cumulative prevalence remained high following initiation of therapy (90%). We found no effect of ART on monthly HPV DNA detection (prevalence ratio: 1.0; 95% confidence interval: 0.96, 1.08), regardless of immune reconstitution or HIV viral suppression. Older age and higher pre-ART CD4 counts were associated with a significantly lower risk of HPV DNA detection.</p> <h3>Conclusions</h3><p>ART did not impact HPV detection within 6 months of therapy initiation, highlighting the importance of continued and consistent screening, even after ART-initiation and immune reconstitution.</p> </div

Prevalence ratios for detection of any type HPV per visit per women in the pre-ART, post-ART and pre-vs. post-ART periods.

<p>Abbreviations: human papillomavirus (HPV); number (N), percent (%); prevalence ratio (PR); confidence interval (CI); antiretroviral therapy (ART); zidovudine (AZT); lamivudine (3TC); nevirapine (NVP); Combivir (CBV); efavirenz (EFV); stavudine (D4T); tenofovir (TDF); Truvada (TVD).</p>a<p>Random effects log-binomial regression to estimate the prevalence ratio of HPV detection by covariates within and across study period, to account for repeated observations on the same women over time.</p>b<p>Early pre-ART refers to 4–6 months before ART initiation and late pre-ART refers 1–3 months before initiation. Early post-ART refers to 1–3 months after initiation and late post-ART refers to 4–6 months after initiation. No significant interactions were found between ART initiation and other covariates (at p≤0.10).</p>c<p>Immune reconstitution: CD4 count increase of 50 or more cells/µL from the pre- to post-ART measurement.</p

Changes in HPV detection by changes in pre-vs. post-ART CD4 counts.

<p>Abbreviations: human papillomavirus (HPV); number (N); standard deviation (STD); interquartile range (IQR); antiretroviral therapy (ART).</p>a<p>Change less than 0 implies that there was a decrease in the variable from the pre- to post-ART period.</p>b<p>Change ≤0 implies that the CD4 cell count taken within 2–9 months after ART initiation was lower than the CD4 count taken within 6 months before ART initiation.</p

Pattern of high- and low-risk monthly HPV detection and median number of HPV [in brackets] types during the pre- and post-ART initiation periods.

<p>Abbreviations: infection with only low-risk human papillomavirus types (LR-HPV); high-risk human papillomavirus types alone or with LR-HPV types (HR-HPV).</p

Characteristics of the female study population (N = 96).

<p>Abbreviations: interquartile range (IQR); number (n); percent (%); antiretroviral therapy (ART); zidovudine (AZT); lamivudine (3TC); nevirapine (NVP); Combivir (CBV); efavirenz (EFV); stavudine (D4T); tenofovir (TDF); Truvada (TVD).</p>a<p>Immune reconstitution: CD4 count increase of 50 or more cells/µL from the pre- to post-ART measurement. Six women did not have follow-up CD4 counts in the 2–9 month post-ART window so immune reconstitution could not be calculated.</p>b<p>HIV virologic suppression: undetectable HIV-1 viral load (<400 copies/mL) in the post-ART period. Seven women did not have follow-up CD4 counts in the 2–9 month post-ART window so immune reconstitution could not be calculated.</p

Cross-classification of cumulative HPV infection status in the 6 months before compared to after ART initiation.

<p>Abbreviations: infection with only low-risk human papillomavirus types (LR-HPV); high-risk human papillomavirus types alone or with LR-HPV types (HR-HPV).</p