Highly active antiretroviral therapy (HAART) may be associated with adverse pregnancy outcomes. Among 4372 live births in the European Collaborative Study, the prematurity rate increased to 24.9% in 2000-2004. Antenatal HAART use initiated pre-pregnancy was strongly associated with prematurity (AOR 2.05, 95% CI 1.43, 2.95), particularly severe prematurity. The implication of increased prematurity is evidenced in high neonatal mortality in these groups (0.66% for infants at 34-36 weeks and 7.37% at < 34 weeks' gestation).
Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life ( <.001). There was no evidence of an association with clinical manifestations suggestive of mitochondrial abnormalities. The absence of serious adverse events in this large cohort of uninfected children exposed to prophylactic ART in the short to medium term is reassuring.
Background
A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH.
Methods
PLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations.
Results
We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296–552)/mm3, 936 (670–1304)/mm3, and 0.43 (0.28–0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2–37) and 18 (7–42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23–3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58–6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60–6.56] for KS; HR = 5.28 [95% CI = 2.17–12.83] for NHL).
Conclusions
Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.
The advent of highly active antiretroviral therapy has facilitated the virtual elimination of mother-to-child transmission of HIV infection in developed countries, reducing transmission rates to approximately 1 to 2%. In these settings, highly active antiretroviral therapy has also transformed pediatric HIV infection into a chronic disease; although there are associated costs in terms of side effects and the heavy pill burden. In less developed settings, easier-to-use adaptations of antiretroviral therapy regimens, such as short-course and single-dose antiretroviral strategies or neonatal postexposure prophylaxis can also substantially prevent mother-to-child transmission, although to a lesser degree than highly active antiretroviral therapy. However, postnatal transmission of infection through breastfeeding significantly reduces the longer-term efficacy of these strategies. Ongoing research is focusing on the use of antiretroviral therapy in the breastfeeding period.
HIV-infected pregnant women are at increased risk of post-partum complications regardless of mode of delivery, but modification of clinical practice, particularly use of prophylactic antibiotics, would reduce this risk. Infected women should be informed about risks of vertical transmission and post-partum complications, and be involved in mode of delivery decisions.
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