Role of antenatal plasma cytomegalovirus DNA levels on pregnancy outcome and HIV-1 vertical transmission among mothers in the University of Zimbabwe birth cohort study (UZBCS)

Abstract

Introduction Despite being a leading infectious cause of childhood disability globally, testing for cytomegalovirus (CMV) infections in pregnancy is generally not done in Sub-Sahara Africa (SSA), where breastfeeding practice is almost universal. Whilst CMV and human immunodeficiency virus (HIV) are both endemic in SSA, the relationship between antenatal plasma CMV-DNA, HIV-1-RNA levels and HIV-1-mother to child transmission (MTCT) including pregnancy outcomes remains poorly described. Methods Pregnant women at least 20 weeks’ gestational age at enrolment were recruited from relatively poor high-density suburbs in Harare, Zimbabwe. Mother-infant dyads were followed up until 6 months postpartum. In a case–control study design, we tested antenatal plasma CMV-DNA levels in all 11 HIV-1 transmitting mothers, as well as randomly selected HIV-infected but non-transmitting mothers and HIV-uninfected controls. CMV-DNA was detected and quantified using polymerase chain reaction (PCR) technique. Antenatal plasma HIV-1-RNA load was quantified by reverse transcriptase PCR. Infants’ HIV-1 infection was detected using qualitative proviral DNA-PCR. Predictive value of antenatal plasma CMV-DNAemia (CMV-DNA of > 50 copies/mL) for HIV-1-MTCT was analyzed in univariate and multivariate regression analyses. Associations of CMV-DNAemia with HIV-1-RNA levels and pregnancy outcomes were also explored. Results CMV-DNAemia data were available for 11 HIV-1 transmitting mothers, 120 HIV-infected but non-transmitting controls and 46 HIV-uninfected mothers. In a multivariate logistic regression model, we found a significant association between CMV-DNAemia of > 50 copies/mL and HIV-1 vertical transmission (p = 0.035). There was no difference in frequencies of detectable CMV-DNAemia between HIV-infected and -uninfected pregnant women (p = 0.841). However, CMV-DNA levels were higher in immunosuppressed HIV-infected pregnant women, CD4 < 200 cells/µL (p = 0.018). Non-significant associations of more preterm births (< 37 weeks, p = 0.063), and generally lower birth weights (< 2500 g, p = 0.450) were observed in infants born of HIV-infected mothers with CMV-DNAemia. Furthermore, in a multivariate analysis of HIV-infected but non-transmitting mothers, CMV-DNAemia of > 50 copies/mL correlated significantly with antenatal plasma HIV-1-RNA load (p = 0.002). Conclusion Antenatal plasma CMV-DNA of > 50 copies/mL may be an independent risk factor for HIV-1-MTCT and higher plasma HIV-1-RNA load, raising the possibility that controlling antenatal CMV-DNAemia might improve infant health outcomes. Further studies with larger sample sizes are warranted to confirm our findings.

Predictors and Timing to Viral Suppression in HIV-Infected Pregnant Women in the University of Zimbabwe Birth Cohort Study During the Era of Lifelong Antiretroviral Therapy (Option B+ Treatment Strategy)

“…This was expected as the latter group had been on ART for long enough time to facilitate optimal ART exposure to enable complete VS. In any case, LLV is clinically highly relevant since HIV MTCT may occur within this LLV range (31)(32)(33), possibly in the presence of coinfections like cytomegalovirus (34). It is therefore essential to evaluate LLV among pregnant women on ART for factors that contribute to failure of reaching undetectable VL.…”

Mother-to-Child Transmission of HIV Within 24 Months After Delivery in Women Initiating Lifelong Antiretroviral Therapy Pre/Post-Conception or Postnatally; Effects of Adolescent Girl and Young Woman Status and Plasma Viremia Late in Pregnancy

“…In our study, interestingly, none of the mothers with low-level viremia VL: 51-1,000 copies/ml late in pregnancy transmitted perinatally. Low-level viremia has been shown to have positive clinical significance in terms of reduced MTCT rates (55). It is therefore imperative that MLWHA commence ART in early pregnancy to suppress HIV RNA to undetectable levels as rapidly as possible to reduce the risk of MTCT (56).…”