Congenital and Postnatal CMV and EBV Acquisition in HIV-Infected Zimbabwean Infants

Abstract

BackgroundHIV-infected infants in sub-Saharan Africa have rapid disease progression. We hypothesized that co-infection with cytomegalovirus (CMV) or Epstein Barr virus (EBV) increases mortality in HIV-infected infants.Methods257 antiretroviral therapy-naïve HIV-infected Zimbabwean infants were tested for CMV and EBV at 6 weeks of age by real-time PCR; if positive, birth samples were retrieved where available to distinguish congenital and postnatal infection. The impact of co-infection on mortality through 6 months was estimated using Kaplan-Meier and Cox proportional hazards methods.ResultsAt 6 weeks, 203/257 (79%) HIV-infected infants were CMV-positive; 27 (11%) had congenital CMV, 108 (42%) postnatal CMV and 68 (26%) indeterminate timing of infection. By 6 months, 37/108 (34%) infants with postnatal CMV versus 16/54 (30%) CMV-negative infants died (adjusted hazard ratio (aHR) 1.1 [95%CI 0.6, 2.2]). At 6 weeks, 33/257 (13%) HIV-infected infants had EBV co-infection; 6 (2%) had congenital EBV, 18 (7%) postnatal EBV and 9 (4%) indeterminate timing of infection. By 6 months, 5/18 (28%) infants with postnatal EBV versus 72/224 (32%) EBV-negative infants died (aHR 0.8 [95%CI 0.3, 2.3]).ConclusionsThe vast majority of HIV-infants had acquired CMV by 6 weeks, and EBV co-infection occurred earlier than expected, with one in eight HIV-infected infants positive for EBV by 6 weeks. There was a high prevalence of congenital CMV infection and we identified 6 infants with congenital EBV infection, which has not previously been reported in Africa or in the context of HIV infection. Neither CMV nor EBV co-infection was associated with increased mortality.

Review of cytomegalovirus coinfection in HIV-infected individuals in Africa

“…Zimbabwe. 17,35,72 These findings are supported by a much more extensive number of studies in high-income countries. 15,[18][19][20][21]24,98,[105][106][107] Hence, the association between CMV and HIV progression may not just be that advanced HIV disease causes immunosuppression, thereby allowing CMV reactivation by decreasing CD4 cell count.…”

“…This association was also found in 3 South African studies, though with higher thresholds of CMV viremia . Gumbo et al studied CMV coinfection in 257 HIV‐infected infants. They found decreased survival among CMV viremic infants, but the results were not significant.…”

“…Only 8 studies commenting on the impact of CMV coinfection (without diagnosed EOD) and mortality in HIV‐infected individuals were conducted in Africa (Table ). All 8 studies found a higher risk of death in CMV coinfected individuals (measurement of CMV DNA) compared with HIV‐infected alone, though 2 of the studies reported insignificant results …”

“…Several studies reported the prevalence of CMV viremia (cut‐off values ranging from 50 to 200 copies/mL) in different populations with no reported CMV disease symptoms. Detectable CMV DNA in blood in HIV‐infected individuals ranged between 1.8% and 22.6% among adults, and 10% and 79% among infants, and was generally more frequent among HIV‐infected compared with HIV‐noninfected individuals . CMV DNA in blood was typically detected early in life indicating that CMV infection was most often acquired within the first 12 months of life …”

Severe anaemia complicating HIV in Malawi; multiple co-existing aetiologies are associated with high mortality

“…Data on co-infections are very limited in African patients (39–41) and our study is the first to describe the association between co-existing CMV and EBV infections and very severe anaemia (haemoglobin ≤50 g/l). Possible explanations for this association include direct viral inhibition of erythropoiesis (39, 42, 43). The majority of our patients with co-infection had advanced HIV disease (88.5%) but the association between EBV and CMV co-infection and very severe anaemia remained significant even after correction for advanced HIV disease.…”