BackgroundLittle is known on outcomes after transition to adult care among adolescents with perinatal HIV infection. Though there is data from other chronic pediatric diseases suggesting increased morbidity and mortality following transfer to adult care, this has not well been studied among the first wave of survivors of perinatal HIV infection. The primary objective of this study was to determine outcomes after transition to adult care among a cohort of HIV-infected adolescents in Québec, Canada. Secondary objectives were to document participant experiences with the transition process, identify barriers to successful transition, and potential changes to improve the transition process.MethodsClinic records were reviewed to identify all perinatally-infected youth who transitioned from the Centre Maternel et Infantile sur le Sida pediatric HIV clinic (Montreal) at age 18 to an adult care provider between 1999 and 2012. Transitioned patients were contacted using last available patient or parental listed phone number on hospital record, internet based telephone directory, or social media. A standardized questionnaire was administered by telephone or in-person interview, and copies of current medical records obtained from treating physicians.ResultsForty-five patients were transferred between 1999 and 2012, among whom 25 consented to the study, eight were lost to follow-up, eight refused participation, and four were deceased. Overall 76 % of patients remained engaged in care, defined by at least one physician visit within 6 months of the interview. Over 50 % reported difficulty with adherence to their current drug regimens. At one-year post-transfer, there was a decrease in the proportion of patients with CD4 count >500 cells/mm3 from 64 to 29 %, and a statistically significant decrease in absolute CD4 count (mean 370 vs 524 cells/mm3, p = 0.04.). The majority (92 %) of participants felt that 18 was too young an age to transfer to adult care, and provided suggestions for improving the transition process.ConclusionsThis group of perinatally-infected youth remained engaged in care after transition, however difficulties with adherence and assuming responsibility for their own care were identified as issues in their post-transition care. The high rate of mortality among them and the changes to their health status post-transition suggest that further work is necessary to document the health outcomes of this group in larger, more diverse cohort settings.

HIV-exposed uninfected (HEU) infants experience increased overall mortality from infectious causes when compared to HIV-unexposed uninfected (HU) infants. This is the case in both the resource-rich and resource-limited settings. Here, we explore the concept that specific types of infectious diseases that are more common among HEU infants could provide clues as to the potential underlying immunological abnormalities. The most commonly reported infections in HEU vs. HU infants are caused by encapsulated bacteria, suggesting the existence of a less effective humoral (antibody, complement) immune response. Decreased transplacental transfer of protective maternal antibodies has consistently been observed among HEU newborns, suggesting that this may indeed be one of the key drivers of their susceptibility to infections with encapsulated bacteria. Reassuringly, HEU humoral response to vaccination appears to be well conserved. While there appears to be an increase in overall incidence of acute viral infections, no specific pattern of acute viral infections has emerged; and although there is evidence of increased chronic viral infection from perinatal transmission of hepatitis C and cytomegalovirus, no data exist to suggest an increase in adverse outcomes. Thus, no firm conclusions about antiviral effector mechanisms can be drawn. However, the most unusual of reported infections among the HEU have been opportunistic infections, suggesting the possibility of underlying defects in CD4 helper T cells and overall immune regulatory function. This may relate to the observation that the immunological profile of HEUs indicates a more activated T cell profile as well as a more inflammatory innate immune response. However, both of these observations appear transient, marked in early infancy, but no longer evident later in life. The causes of these early-life changes in immune profiles are likely multifactorial and may be related to in utero exposure to HIV, but also to increased environmental exposure to pathogens from sicker household contacts, in utero and postnatal antiretroviral drug exposure, and, in certain circumstances, differences in mode of feeding. The relative importance of each of these factors will be important to delineate in an attempt to identify those HEU at highest risk of adverse outcomes for targeted interventions.

BackgroundThe risk of pre-term birth (PTB) associated with the use of protease inhibitors (PIs) during pregnancy remains a subject of debate. Recent data suggest that ritonavir boosting of PIs may play a specific role in the initiation of PTB, through an effect on the maternal–fetal adrenal axis. The primary objective of this study is to compare the risk of PTB among women treated with boosted PI versus non-boosted PIs during pregnancy.MethodsBetween 1988 and 2011, 705 HIV-positive women were enrolled into the Centre Maternel et Infantile sur le SIDA mother–infant cohort at Centre Hospitalier Universitaire Sainte-Justine in Montreal, Canada. Inclusion criteria for the study were: 1) attendance at a minimum of two antenatal obstetric visits and 2) singleton live birth, at 24 weeks gestational or older. The association between PTB (defined as delivery at <37 weeks gestational age), antiretroviral drug exposure and maternal risk factors was assessed retrospectively using logistic regression.ResultsA total of 525 mother–infant pairs were included in the analysis. Among them, PI-based combination anti-retroviral therapy was used in 37.4%, boosted PI based in 24.4%, non-nucleoside reverse transcriptase inhibitor (NNRTI) or nucleoside reverse transcriptase inhibitor based in 28.1%, and no treatment was given in 10.0% of cases. Overall, 13.5% of women experienced PTB. Among women treated with antiretroviral therapy, the risk of PTB was significantly higher among women who received boosted versus non-boosted PI (OR 2.01, 95% CI 1.02–3.97). This remained significant after adjusting for maternal age, delivery CD4 count, hepatitis C co-infection, history of previous PTB, and parity (aOR 2.17, 95% CI 1.05–4.51). There was no increased risk of PTB with the use of unboosted PIs as compared to NNRTI- or NRTI-based regimens.ConclusionWhile previous studies on the association between PTB and PI use have generally considered all PIs the same, our results would indicate a possible role of ritonavir boosting as a risk factor for PTB. Further work is needed to understand the pathophysiologic mechanisms involved, and to identify the safest ARV regimens to be used in pregnancy.