Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda.

Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNA viral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre-ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding

Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda.

Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNA viral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre-ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding

Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda

Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNA viral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre-ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding

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

Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment.

Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation

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