Sandra Hernández

Increased risk of pre-eclampsia and fetal death in Hiv-infected pregnant women receiving highly active antiretroviral therapy

Background:Pre-eclampsia and/or fetal death have increased sharply in HIV-infected pregnant women receiving HAART. Methods:The occurrence of pre-eclampsia or fetal death was analysed in women who delivered after at least 22 weeks of gestation for all women (January 2001 until July 2003) and for HIV-infected women (November 1985 until July 2003). Results:In 2001, 2002 and 2003, the rates per 1000 deliveries of pre-eclampsia and fetal death, respectively, remained stable in all pregnant women at 25.4, 31.9 and 27.7 (P = 0.48) and 4.8, 5.8, and 5.0 (P = 0.89) (n = 8768). In 1985–2000 (n = 390) to 2001–2003 (n = 82), rates per 1000 deliveries in HIV-infected women rose from 0.0 to 109.8 (P < 0.001) for pre-eclampsia and from 7.7 to 61.0 (P < 0.001) for fetal death. In all pregnant women, factors associated with pre-eclampsia or fetal death were multiple gestation [adjusted odds ratio (OR) 3.6; 95% confidence interval (CI), 2.3–5.6; P < 0.001], HIV infection (adjusted OR, 4.9; 95% CI, 2.4–10.1; P < 0.001), multiparity (adjusted OR, 0.76; 95% CI, 0.58–0.98; P = 0.040) and tobacco smoking (adjusted OR, 0.65; 95% CI, 0.46–0.90; P = 0.010). The use of HAART prior to pregnancy (adjusted OR, 5.6; 95% CI, 1.7–18.1; P = 0.004) and tobacco smoking (adjusted OR, 0.183; 95% CI, 0.054–0.627; P = 0.007) were risk factors in HIV-infected women. Conclusions:HIV infection treated with HAART prior to pregnancy was associated with a significantly higher risk for pre-eclampsia and fetal death.

Association of HIV infection with spontaneous and iatrogenic preterm delivery: effect of HAART.

Objectives:To assess the association between HIV infection and both spontaneous and iatrogenic preterm delivery (PTD), and to explore the impact of HAART on both entities. Methods:A matched retrospective cohort study was carried out on 517 HIV-infected pregnant women who consecutively attended a university referral hospital between 1986 and 2010. Two controls were assigned for each case. They were matched by ethnicity, smoking, maternal age and educational level. Exclusion criteria were multiple pregnancy and active injection drug use (IDU). PTD was defined as delivery less than 37.0 weeks. Spontaneous PTD included preterm premature rupture of membranes. Iatrogenic delivery was considered if medically indicated. Factors associated with PTD among HIV-infected women were analyzed by logistic regression. Results:A total of 1557 pregnant women were analyzed (519 HIV-infected and 1038 noninfected). The incidence of PTD was 19.7% in HIV-infected women and 8.5% in controls [odds ratio (OR) 2.6; 95% CI 1.9–3.6]. There was a significantly higher incidence of both spontaneous [adjusted OR (AOR) 2.1; 95% confidence interval (CI) 1.5–3.0] and iatrogenic prematurity (AOR 3.2; 95% CI 1.8–5.7). Iatrogenic PTD was significantly associated with the use of HAART during the second half of pregnancy, whereas spontaneous PTD was not related to HAART. Conclusion:There is a significant association of HIV infection with PTD, both spontaneous and iatrogenic PTD. HAART use was predominantly associated with iatrogenic PTD.

Visual analysis of antepartum fetal heart rate tracings: inter- and intra-observer agreement and impact of knowledge of neonatal outcome

Abstract Objective: To evaluate the inter- and intra-observer agreement of visual analysis of fetal heart rate tracing and to evaluate the bias introduced by knowledge of perinatal outcome in this interpretation. Methods: One hundred tracings were independently analyzed by four observers. In a second study period, two observers re-analysed the 100 tracings in order to evaluate intra-observer agreement. The other two observers re-analyzed the tracings, which were labelled with fictitious perinatal outcome to evaluate the impact of this information on reliability. Agreement was analyzed by means of the proportion of agreement for qualitative parameters and the inter- and intra-class correlation coefficient for quantitative data. Results: Poor agreement was found for quantitative variability, low variability category and number of decelerations. Moderate agreement was observed for baseline, normal variability category and number of accelerations. Fetal heart rate variability and number of accelerations and decelerations were found to be significantly influenced by clinical information of perinatal outcome. Biased observers showed lower reliability than unbiased ones. Conclusion: Visual assessment of fetal heart rate tracings is unreliable due to low rates of agreement between and within observers. Only qualitative classification such as normal baseline and normal variability showed good agreement. Knowledge of clinical information introduces subjectivity to the visual analysis, leading to a negative impact on reliability.

Fertility assessment in non-infertile HIV-infected women and their partners

The objective of the study was to assess the fertility of non-infertile couples seeking pregnancy in whom the woman was HIV infected. Therefore, a cross-sectional study was conducted between January 1998 and March 2005. A standardized fertility assessment was performed in all the included couples. A total of 130 women and 121 men were evaluated. Their median age was 34 years (range 22-43). Only 7.2% of the women were severely immunocompromised. The majority of women had regular cycles. Only one woman had an active sexually transmitted disease at the time of evaluation. A tubal occlusion on hysterosalpingogram was present in 27.8% of the women with no proven fertility. In 50.5% of the women, hepatitis C virus co-infection was present. One-third of the male partners (38/121) was infected with HIV. Abnormal semen parameters were observed in 83.4% of HIV-infected and 41.7% of HIV-uninfected partners (OR = 7; 95% CI = 2.1-23). It is concluded that the great majority of the HIV-infected women seeking pregnancy had a good infection status. Because in many of the couples, the women presented unexplained tubal occlusions and the men presented semen alterations, a hysterosalpingography and semen analysis should be part of the preconceptional investigations.

Perinatal outcomes, mitochondrial toxicity and apoptosis in HIV-treated pregnant women and in-utero-exposed newborn

Objective:Highly active antiretroviral therapy (HAART) has decreased the risk of HIV mother-to-child transmission. However, HIV and HAART have been associated with adverse perinatal outcome. HAART has been associated with mitochondrial dysfunction in nonpregnant adults, and HIV, additionally, to apoptosis. We determined whether mitochondrial toxicity and apoptosis are present in HIV-pregnant women and their newborns and could be the basis of adverse pregnancy outcome. Design:Single-site, cross-sectional, controlled observational study without intervention. Methods:We studied mitochondrial and apoptotic parameters in mononuclear cells from maternal peripheral blood and infant cord blood at delivery in 27 HIV-infected and treated pregnant women, and 35 uninfected controls and their infants, to correlate clinical outcome with experimental findings: mitochondrial number (CS), mtDNA content (ND2/18SrRNA), mitochondrial protein synthesis (COX-II/V-DAC), mitochondrial function (enzymatic activities) and apoptotic rate (caspase-3/&bgr;-actin). Results:Global adverse perinatal outcome, preterm births and small newborn for gestational age were significantly increased in HIV pregnancies [odds ratio (OR) 7.33, 5.77 and 9.71]. Mitochondrial number was unaltered. The remaining mitochondrial parameters were reduced in HIV mothers and their newborn; especially newborn mtDNA levels, maternal and fetal mitochondrial protein synthesis and maternal glycerol-3-phosphate + complex III function (38.6, 25.8, 13.6 and 31.2% reduced, respectively, P < 0.05). All materno-fetal mitochondrial parameters significantly correlated, except mtDNA content. Apoptosis was exclusively increased in infected pregnant women, but not in their newborn. However, adverse perinatal outcome did not correlate mitochondrial or apoptotic findings. Conclusions:Transplacental HAART toxicity may cause subclinical mitochondrial damage in HIV-pregnant women and their newborn. Trends to increased maternal apoptosis may be due to maternal-restricted HIV infection. However, we could not demonstrate mitochondrial or apoptotic implication in adverse perinatal outcome.

Fertility choices and management for Hiv-positive women

Purpose of reviewIt is becoming increasingly important to address the issue of reproductive counselling and management of HIV-infected individuals during their reproductive years. Sexual and reproductive health-related needs and aspirations are similar to those of uninfected individuals but some differences require specific attention, which are discussed in this review. Recent findingsHormonal contraception should be used with caution in women on antiretroviral treatment. Its impact on both HIV infectivity and disease progression is still controversial. An intrauterine device can be considered for pregnancy prevention and pregnancy termination should be offered in safe conditions. HIV-infected women have a lower spontaneous fertility rate, which may persist after assisted reproduction. Data on safety of antiretroviral treatment during conception are reassuring. No clear association can be found between exposure to antiretrovirals and fetal abnormalities. Secondary prevention remains crucial and condom use remains a key method. SummaryDifferent topics related to fertility choices among HIV-infected patients should be addressed. Family planning methods and termination of pregnancy have specific aspects among infected individuals. When needed, medically assisted reproduction may be required and antiretroviral treatment should be adapted before conception. Secondary prevention has a key role in reducing newly acquired infections.

Current guidelines on management of HIV-infected pregnant women: Impact on mode of delivery

OBJECTIVE To evaluate acceptance, feasibility and difficulties in the application of a policy of vaginal delivery in selected cases in HIV-infected women. STUDY DESIGN HIV-infected women delivering March 2002 to December 2004 and enrolled in a prospective observational study in a University hospital tertiary care center were included. A vaginal delivery was not considered if labor before 36 weeks of pregnancy, preterm premature rupture of membranes, on non-highly active antiretroviral therapy (HAART) or viral load >1000copies/mL. Main outcome measures were mode of delivery, prematurity, acceptance of vaginal delivery and mother-to-child transmission of HIV infection. RESULTS The study included 91 pregnancies, with a total of 95 fetuses. Eighty percent (n=73) of women knew their HIV infection status before becoming pregnant and 57 (63%) were on HAART at conception. Median gestational age at delivery was 37 weeks (range 22-41). Twelve women delivered a live-born before 36 weeks, all with a caesarean section. Among 74 women who reached 36 weeks gestation, 47 (64%) met the pre-established criteria for vaginal delivery, of whom 21 (45%) delivered vaginally. The most common reason for not having a vaginal delivery was the womans request for a caesarean section. No cases of HIV vertical transmission occurred (0/90, 95% CI 0-4.02%). CONCLUSION Recommending vaginal delivery among HIV-infected women in selected cases was well accepted, particularly once the policy became established. Nevertheless, a high proportion of HIV-infected women will continue to require caesarean section delivery.

Mitochondrial disturbances in HIV pregnancies.

Background:Mitochondrial consequences from foetal exposure to HIV infection and antiretrovirals could be further investigated. Objective:The main objective of this study was to evaluate maternofoetal mitochondrial disturbances in HIV infection and antiretroviral administration in human pregnancies as the aetiopathogenic basis of suboptimal perinatal-clinical features. Design:Cross-sectional, prospective, observational, exploratory and controlled study. Methods:Clinical/epidemiological data of 35 HIV-infected pregnant women and 17 controls were collected. Mitochondrial DNA (mtDNA) and RNA (mtRNA) content (real time-PCR), enzymatic activities and content (spectrophotometry) were measured in leucocytes. Genetic-functional, maternofoetal and molecular-clinical correlations were assessed. Results:Birth weight was lower in infants from HIV-infected mothers compared with controls. MtDNA values were slightly decreased in HIV cases, although not reaching statistical significance. MtRNA values were lower in HIV-infected mothers. Similarly, binary complex II+III enzymatic activity decreased to 50% in both HIV-infected mothers (44.45 ± 3.77%) and their infants (48.79 ± 3.41%) (P = 0.001 and P < 0.001). Global CI+III+IV enzymatic activity was lower in HIV-infected mothers and infants (90.43 ± 2.39% and 51.16 ± 9.30%) (P < 0.005 and P < 0.05). MtDNA content correlated with function in mothers and infants. Maternofoetal parameters correlated at genetic and functional levels. Conclusion:HAART toxicity caused mitochondrial damage in HIV-infected pregnant women and their newborns, being present at a genetic and functional level with a maternofoetal correlation.

Mitochondrial impact of human immunodeficiency virus and antiretrovirals on infected pediatric patients with or without lipodystrophy.

We determined the mitochondrial status of a group of HIV-infected children, some with body fat abnormalities (BFA). We included 24 controls, 16 HIV-infected untreated, 26 HIV-infected treated, 6 BFA-untreated, and 21 BFA-treated patients. Genetic, translational, and functional mitochondrial values were measured. As compared with controls, mitochondrial DNA depletion and a reduction in functionality were found in BFA groups.

Study of oxidative, enzymatic mitochondrial respiratory chain function and apoptosis in perinatally HIV-infected pediatric patients.

Abstract Mitochondrial toxicity in perinatally human immunodeficiency virus (HIV)-infected pediatric patients has been scarcely investigated. Limited data are available about HIV or antiretroviral (ARV)-mediated mitochondrial damage in this population group, specifically, regarding oxygen consumption and apoptosis approach. We aimed to elucidate whether a given mitochondrial DNA depletion is reflected at downstream levels, to gain insight on the pathology of HIV and highly active antiretroviral therapy (HAART) in perinatally HIV-infected pediatric patients. We studied 10 healthy control participants and 20 perinatally HIV-infected pediatric patients (10 under ARV treatment and 10 off treatment). We determined mitochondrial mass, subunits II and IV of complex IV, global and specific mitochondrial enzymatic and oxidative activities, and apoptosis from peripheral blood mononuclear cells. Global oxygen consumption was significantly compromised in HIV-infected untreated patients, compared to the control group (0.76 ± 0.01 versus 1.59 ± 0.15; P = 0.014). Apoptosis showed a trend to increase in untreated patients as well. The overall complex (C) CI-III-IV activity of the mitochondrial respiratory chain (MRC) was significantly decreased in HIV-infected treated patients with respect to the control group (1.52 ± 0.38 versus 6.38 ± 1.53; P = 0.02). No statistically significant differences were found between untreated and HAART-treated patients. These findings suggest the pathogenic role of both HIV and HAART in mitochondrial dysfunction in vertical infection. The abnormalities in mitochondrial genome may be downstream reflected through a global alteration of the MRC. Mitochondrial impairment associated with HIV and HAART was generalized, rather than localized, in this series of perinatally HIV-infected patients.