Levels of CMV antibody are linked to HIV progression and immune activation in Ugandan women

Levels of anti-CMV IgG antibodies in the blood were associated with HIV disease progression and increased markers of immune activation in a Ugandan cohort of untreated women with HIV.

The results were reported from a prospective cohort study in participants of an acyclovir trial, by Eshan Patel and colleagues in the journal AIDS. [1]

CMV co-infection has been reported in numerous studies to increase HIV disease progression, which is likely to result from bidirectional antagonism between the two infections: HIV mediated immunosuppression leads to increased CMV activity which contributes to greater immune activation and HIV replication. [2, 3]

Patel and colleagues used plasma anti-CMV IgG antibody titres as an indirect measure of CMV activity and assessed its relationship with CD4 cell counts, HIV viral load, plasma C-reactive protein (CRP), plasma soluble CD14 (sCD14) as well as the study primary endpoints. Primary endpoints were time to starting ART, reaching a CD4 cell count <250 cells/mm³ or non-traumatic death. CRP is a measure of generalised immune activation while sCD14 is a measure of monocyte activation.

CMV IgG was measured at baseline in all women, and then annually among a subset of women who initiated ART during the study. CD4 count, viral load, plasma CRP and sCD14 were measured bi-annually for 24 months.

Overall, 300 women with HIV/CMV coinfection contributed 426 person years of follow-up (with a median of 1.8 years) There was a positive association between increasing CMV IgG titres and viral load, sCD14 and CRP at enrolment (p = 0.05).

Of the 300 study participants, 150 reached a primary end point. CMV antibody titres across the cohort were divided into tertiles. Compared to women in the lowest CMV IgG tertile at baseline, women in the highest tertile had a significantly increased probability of reaching a primary endpoint (p <0.001), as well as an increased relative hazard of disease progression (HR 2.21; 95%CI: 1.49 to 3.27, p <0.001). The relationship was independent of acyclovir study arm, age, baseline CD4 count or viral load.

In an analysis of 1,200 person visits that excluded post ART-initiation data, women in the baseline high CMV IgG tertile experienced annual increases in sCD14 (p = 0.022) and CRP (p = 0.001). In contrast, women in the lowest tertile experienced annual decreases in sCD14 (p = 0.022) and no change in CRP. These changes were independent of time-updated CD4 cell counts, viral load, acyclovir study arm or time interaction.

Changes in anti-CMV IgG antibody titre between pre-ART and post-ART were assessed in 70 women. Across the whole group CMV IgG titre increased (p = 0.006). While median time on ART was only 140 days, visit specific analysis was performed for 95 person visits and found that CMV IgG titre above the post-ART median were associated with increased sCD14 (p = 0.019) and CRP (p = 0.028) independently of acyclovir study arm, age, time updated CD4 cell count, or pre-ART CD4 cell count nadir.

The authors conclude that their data supports the hypothesis that CMV may contribute to systemic immune activation during untreated HIV infection. However the associations reported in this concise communication do not imply causality or directionality. In addition, the authors discuss the possibility that increases in CMV IgG titres are not necessarily reflective of increased CMV activity. Secondary to this, while increases in CMV IgG titres after ART may reflect immune reconstitution, they may also be due to subclinical immune reconstitution inflammatory effects.