Plasma efavirenz concentration inversely correlates with increased risk of cytomegalovirus infection in HIV-infected pregnant women

Abstract

Combination antiretroviral therapy (cART) has tremendously reduced HIV-associated morbidity, mortality and mother-to-child transmission (MTCT). [1] The Option B+ (lifelong cART for all HIV-infected pregnant and breastfeeding women) introduced by the World Health Organization proved to be effective, resulting in a reduction of MTCT from 33% (before ART) to <2% in sub-Saharan Africa. [2] Despite the massive success in reduction of MTCT, HIV-exposed uninfected (HEU) children experience delayed developmental milestones, disabilities and more frequent morbidities than their HIV-unexposed counterparts. [3,4] Developmental and health problems in some HEU infants occur despite maternal cART during pregnancy. Differential HIV outcomes have previously been associated with interindividual variation in response to cART. [5] The differential outcomes of cART during pregnancy are critical in the care of HEU infants who have to endure effects of in utero and postpartum exposure to antiretroviral drugs. [6] Furthermore, the increasing number of HIV-infected adolescents who grow into adulthood with a strong will to procreate, further emphasises the need to understand the factors associated with different HIV treatment outcomes in pregnancy, which also determine infant outcomes. [7] Of the utmost importance during pregnancy are antenatal diseases that may result in adverse outcomes if transmitted to the developing fetus or neonate. Antenatal infections (such as cytomegalovirus (CMV), toxoplasmosis, syphilis and rubella) are more prevalent among HIVinfected than HIV-uninfected women. [8,9] CMV is a latent beta herpesvirus that is often reactivated in immunecompromised populations such as HIV patients and pregnant women. When reactivation of CMV occurs during pregnancy, the virus can be transmitted to the fetus and/or neonate, resulting in congenital CMV (cCMV) infection. [10] Effects of cCMV may be potentially fatal and include paediatric pneumonia, neurocognitive developmental delay and sensorineural hearing loss, for which CMV is the leading non-genetic cause. [11,12] In a review by Filteau and Rowland-Jones, [13] vertical transmission of CMV in utero or in early infancy was hypothesised to be responsible for the health and developmental deficits in HIV-exposed children. cCMV is sustained by antenatal CMV infection or reactivation; hence, controlling maternal CMV infection is key in the prevention of cCMV. cART is protective against the emergence of opportunistic infections; [14] therefore, the occurrence of CMV in some but not all HIV-infected This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.