Background:  Progression to AIDS in Sub-Saharan African infants is rapid, but the influence of cytomegalovirus (CMV) on HIV disease progression in resource-limited settings is uncertain.

Methods:  Infants born to HIV-infected mothers in Durban, South Africa, were diagnosed by HIV PCR on days 1 and 28 of life, randomized 2:1 to immediate or deferred antiretroviral therapy (ART) and seen monthly for HIV viral load and CD4 count. Cryopreserved plasma from 3 to 4 months of age was, retrospectively, tested for CMV by PCR. Pre-ART CD4 decline and post-ART CD4 reconstitution were compared between CMV⁺ and CMV^– infants.

Results:  Of 740 infants, 75 were HIV-infected and 63 were enrolled to the study; 12 were ineligible. Disease progression was rapid, with 85% deferred infants reaching CD4 ≤25% by 6 months of age. CMV PCR was undertaken on 54 of 63 (86%) infants; 32 of 54 (59%) were CMV⁺ by median 98 days of life (IQR 88 to 103). CMV⁺ infants were more likely than CMV^– infants to be breastfed (p = 0.01), but there was no difference in infant HIV viral load or maternal disease status. Birth CD4 count was similar between CMV⁺ and CMV^– infants (median 45% in both groups) but CD4 decline from birth was twice as rapid in CMV⁺ compared to CMV^– infants (median 10.5% / month vs 5.0% / month; P=0.007) and pre-ART CD4 nadir was significantly lower (median 21% vs 37%; p <0.0001). There was no effect of CMV or HIV viral load on speed of CD4 decline. Morbidity and mortality were similar between groups but there was a trend towards more failure-to-thrive in CMV⁺ infants (p = 0.07). Strikingly, CD4 counts after 12 months ART remained significantly lower in CM^V+ compared to CMV^– infants (median 29% vs 36%; p = 0.004).

Conclusions:  CMV infection doubles the speed of HIV disease progression in Sub-Saharan African infants. The role of CMV as a co-factor in resource-limited settings has hitherto been overlooked. Over half of HIV-infected infants acquired CMV in the first 4 months of life, and these infants had more rapid CD4 decline and reduced CD4 reconstitution on ART. The speed of disease progression in dual-infected infants highlights the urgency of early HIV diagnosis and ART initiation in this setting and raises the possibility of CMV treatment as a means of slowing disease progression and improving immune reconstitution in HIV-infected African infants.