Pregnant women co-infected with HIV and Zika: Outcomes and birth defects in infants according to maternal symptomatology

Abstract

BackgroundZika virus (ZIKV) was first isolated in Uganda in 1947. In Brazil, the first reported case of ZIKV infection was in May 2015. Additionally, dengue (DENV) is endemic and there has been a recent outbreak of chikungunya (CHIKV). Since the clinical manifestations of different arboviral infections (AI) can be similar, definitive diagnosis requires laboratory testing.ObjectivesTo determine the prevalence of ZIKV, DENV, and CHIKV infections in a Brazilian cohort of HIV-infected pregnant women, to assess clinical/immunological characteristics and pregnancy outcomes of women with evidence of recent AI.Study designLaboratory diagnosis of ZIKV, DENV and CHIKV infections utilized serological assays, RT-PCR and PRNT. The tests were performed at the first visit, 34–36 weeks of gestation and at any time if a woman had symptoms suggestive of AI. Mann-Whitney tests were used for comparison of medians, Chi-square or Fisher’s to compare proportions; p< 0.05 was considered statistically significant. Poisson regression was used to analyze risk factors for central nervous system (CNS) malformations in the infant according to maternal symptomatology.ResultsOf 219 HIV-infected pregnant women enrolled, 92% were DENV IgG+; 47(22%) had laboratory evidence of recent AI. Of these, 34 (72%) were ZIKV+, nine (19%) CHIKV+, and two (4%) DENV+. Symptoms consistent with AI were observed in 23 (10%) women, of whom 10 (43%) were ZIKV+, eight (35%) CHIKV+. No CNS abnormalities were observed among infants of DENV+ or CHIKV+ women; four infants with CNS abnormalities were born to ZIKV+ women (three symptomatic). Infants born to ZIKV+ women had a higher risk of CNS malformations if the mother was symptomatic (RR = 7.20), albeit not statistically significant (p = 0.066).ConclusionsAmong HIV-infected pregnant women with laboratory evidence of a recent AI, 72% were ZIKV-infected. In this cohort, CNS malformations occurred among infants born to both symptomatic and asymptomatic pregnant women with Zika infection.

Fetal, neonatal, and infant outcomes associated with maternal Zika virus infection during pregnancy: A systematic review and meta-analysis

“…The variation in the number of pregnant women in the studies ranged from 28 [ 19 ] to 19,963 [ 39 ]. The overall studies were conducted in the Americas: Brazil [ 25 , 26 , 29 , 33 , 34 , 38 ], Puerto Rico [ 18 ], United States of America (USA) [ 19 , 21 , 22 , 24 , 35 , 37 , 40 ], Peru [ 30 ], French territories of the Americas: French Guiana, Guadeloupe and Martinique [ 20 , 36 ] and Colombia [ 23 , 27 , 28 , 39 ]. Quality scores for the studies are available in S3 Table .…”

“…The criteria for ZIKV infection followed that recommended by the Center for Disease Control and Prevention (CDC) [ 41 ]: positive RT-PCR in serum or urine or IgM for ZIKV by the enzyme-linked immunosorbent assay (ELISA) method, including the PRNT for the differential diagnosis with other arboviruses. In 11 cohorts, only pregnant women with positive RT-PCR for ZIKV in serum or urine were included [ 23 , 25 – 30 , 33 , 34 , 36 , 39 ] and ten cohorts included pregnant women with RT-PCR confirmed infection for ZIKV in serum or urine and those with probable infection with IgM measurement with PRNT for ZIKV [ 18 – 22 , 24 , 35 , 37 , 38 , 40 ]. In nine studies, only symptomatic pregnant women were included [ 23 , 25 , 27 – 29 , 33 , 34 , 36 , 40 ], in the other 12 studies, both symptomatic and asymptomatic pregnant women were included.…”

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

“…Traveller/non-traveller populations: In this update, we found further evidence that congenital abnormalities occurred in infants born to women travellers returning from ZIKV-affected areas and women remaining in those areas. In total, 25 publications report on 272 congenital abnormalities due to ZIKV infection in travellers 27, 29, 30, 32, 34, 36, 38, 42, 45, 56, 58, 61, 89, 94, 98, 109, 117, 122, 123, 137, 140, 151, 153, 166, 173 , with 109 publications reporting congenital abnormalities due to ZIKV in 2652 non travellers 24– 26, 28, 31, 33, 35, 37, 39– 41, 43, 44, 46– 48, 50, 51, 54, 57, 60, 62– 79, 81, 83– 85, 87, 88, 90– 93, 95– 97, 100, 101, 104– 106, 110– 113, 115, 116, 118, 119, 121, 124– 135, 142– 147, 149, 152, 154, 156– 164, 167, 168, 171, 172, 175– 180, 182, …”

SIV/SHIV-Zika co-infection does not alter disease pathogenesis in adult non-pregnant rhesus macaque model

“…Recent studies have revealed a significant increase in the number of HIV-ZIKV co-infected individuals reported in endemic areas in America [ 20 – 23 ] and Africa [ 24 ]. Additionally, the National Institute of Health (NIH) initiated an international, multisite clinical study, “Prospective Cohort Study of HIV and ZIKV in Infants and Pregnancy” (HIV ZIP; ClinicalTrials.gov, # NCT03263195) to register 2,000 pregnant women for the purpose of investigating ZIKV/HIV co-infection in the United States, Brazil, and Puerto Rico.…”

“…Additionally, the National Institute of Health (NIH) initiated an international, multisite clinical study, “Prospective Cohort Study of HIV and ZIKV in Infants and Pregnancy” (HIV ZIP; ClinicalTrials.gov, # NCT03263195) to register 2,000 pregnant women for the purpose of investigating ZIKV/HIV co-infection in the United States, Brazil, and Puerto Rico. Further studies suggest that although a high prevalence (72%) of ZIKV among 219 HIV-infected pregnant women was reported [ 20 , 23 ]; their clinical presentation suggested a mild disease with a rapid and complete recovery. However, the fetuses of these women were often born with significant abnormalities, similar to those described previously in the children of women without HIV infection [ 25 ] and fetal demise would often occur [ 20 ].…”