Antiretroviral adherence among people living with HIV during the postpartum period: a retrospective cohort study at a PMTCT reference center in Rio de Janeiro before and during the COVID-19 pandemic.

Despite success in achieving viral suppression during pregnancy in people living with HIV (PLWH), postpartum adherence remains a challenge. We aimed to describe rates of adherence at a Prevention of Mother-to-Child HIV Transmission (PMTCT) Center before and during the COVID-19 pandemic. This study was conducted from a cohort of PLWH who received prenatal care and were virally suppressed near delivery. We tracked combined antiretroviral therapy (cART) pickups for 12 months and HIV viral load (VL) from 2 to 12 months after delivery. We defined flexible adherence as a monthly pickup of cART and strict adherence as also having VL < 200 copies/mL and at least one maternal HIV VL between two and twelve months postpartum. Pre-pandemic was defined as delivery from March 2017-February 2019 and pandemic as March 2020-February 2022. During the study, 1119 PLWH were followed, and 965 (86%) were suppressed near delivery. There were 511 pre-pandemic and 290 pandemic participants. Adherence rates were 66/511 (13%) and 38/290 (13%), respectively. During the pandemic, more participants conceived using cART and were undetectable at the start of prenatal care; nevertheless, postpartum adherence was no better than pre-pandemic underscoring the need to improve strategies for adherence specific to this subset of PLWH in the postpartum period.

Resistance rates among antiretroviral regimens in pregnant people living with HIV.

OBJECTIVES: To update nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) resistance rates and describe the frequency of HIV subtypes in a cohort of pregnant people living with HIV (PPLH) at a national Prevention of Mother-To-Child HIV Transmission (PMTCT) centre. METHODS: We evaluated genotypic resistance among PPLH during prenatal care who were antiretroviral therapy-naïve or experienced. We determined mutations by the Surveillance of Drug Resistance Mutations (SDRM) dataset and also focused on studying participants with intermediate or high resistance defined through the Stanford score. RESULTS: From 2018 to 2021, 1170 PPLH received prenatal care at the centre and 550 were genotyped. Among the 295 SDRMs, with respect to NRTI resistance mutations, there were 27/295 (9.2%) M184V/I, 14/295 (4.7%) T215Y/C/D/E/F/V/I/S and 12/295 (4.1%) M41L. For NNRTI, there were 75/295 (25.4%) K103N, 18/295 (6.1%) M230L and 14/295 (4.7%) G190A/E/S mutations. For PI, the most frequent mutations were 13/295 (4.4%) V82A/S/F/T, 12/295 (4.1%) M46I/L and 10/295 (3.4%) D30N. Based on the Stanford score, 36/224 (16%) naïve participants had one or more antiretroviral resistance mutations, 81% of whom had NNRTI resistance. In the treatment-experience group, 108/326 (33%) had one or more mutations, 91% of whom had NNRTI resistance. The most frequent HIV subtype was B (82.5%). CONCLUSIONS: Our findings suggest that continuous surveys of HIV genotype appear to be important tools to map the distribution and evolution of HIV subtypes and resistance to provide information to support treatment policies. Furthermore, concerns about the use of rilpivirine-containing regimens underscore the importance of resistance surveillance.

Real-world experience with weight gain among pregnant women living with HIV who are using integrase inhibitors.

OBJECTIVES: We assessed real-world weight change and pregnancy outcomes among pregnant women living with HIV who used integrase strand transferase inhibitor (INSTI)-based combined antiretroviral therapy (cART). METHODS: In a retrospective cohort study from 2014 to 2021 for prevention of perinatal HIV infection, we evaluated changes in weight from the first prenatal visit to near delivery for two groups. The categories of change were: low (< 0.18 kg/week), normal (0.18-0.59 kg/week), and high (> 0.59 kg/week). The backbones were lamivudine + tenofovir disoproxil or lamivudine + zidovudine. The comparison groups were women with body mass index (BMI) < 25 kg/m2 versus BMI ≥ 25 kg/m2 and INSTI-naïve versus INSTI-experienced. Continuous variables were analysed with a Kruskal-Wallis test and count or categorical data with χ2 tests. RESULTS: We enrolled 198 pregnant women. At study entry, 74 had BMI < 25 kg/m2 and 124 had BMI ≥ 25 kg/m2 . Excess gestational weight gain was more frequent among women who were INSTI-naïve among both BMI groups (< 25 and ≥ 25). However, the proportion of participants per weight change category was only significantly different between INSTI-naïve women with baseline BMI < 25 kg/m2 and INSTI-experienced women with BMI < 25 kg/m2 . In particular, INSTI-naïve women with BMI < 25 kg/m2 had significantly higher rates of excess gestational weight gain (31.6%) compared with participants with BMI < 25 kg/m2 who conceived while on INSTIs (11.8%, p = 0.004). Rates of unfavourable pregnancy outcomes were low and did not differ significantly between groups. CONCLUSIONS: INSTI-naïve participants with BMI < 25 kg/m2 gained more weight during pregnancy than participants with BMI ≥ 25 kg/m2 who conceived while using INSTIs. Rates of adverse pregnancy outcomes did not differ between the groups.

Maternal and Neonatal Outcomes of SARS-CoV-2 Infection in a Cohort of Pregnant Women with Comorbid Disorders.

There are some reports and case series addressing Coronavirus Disease 2019 (COVID-19) infections during pregnancy in upper income countries, but there are few data on pregnant women with comorbid conditions in low and middle income Countries. This study evaluated the proportion and the maternal and neonatal outcomes associated with SARS-CoV-2 infection among pregnant women with comorbidities. Participants were recruited consecutively in order of admission to a maternity for pregnant women with comorbidities. Sociodemographic, clinical, and laboratory data were prospectively collected during hospitalization. Pregnant women were screened at entry: nasopharyngeal swabs were tested by RT-PCR; serum samples were tested for IgG antibodies against spike protein by ELISA. From April to June 2020, 115 eligible women were included in the study. The proportion of SARS-CoV-2 infection was 28.7%. The rate of obesity was 60.9%, vascular hypertension 40.0%, and HIV 21.7%. The most common clinical presentations were ageusia (21.2%), anosmia (18.2%), and fever (18.2%). Prematurity was higher among mothers who had a SARS-CoV-2 infection based on RT-PCR. There were two cases of fetal demise. We found a high proportion of COVID-19 among pregnant women with comorbidities. This underscores the importance of antenatal care during the pandemic to implement universal SARS-CoV-2 screening, precautionary measures, and the rollout of vaccination programs for pregnant women.

Efficacy of Three Antiretroviral Regimens Initiated during Pregnancy: Clinical Experience in Rio de Janeiro.

Few studies have compared the clinical efficacy and adverse events of combined antiretroviral therapy (cART) regimens in pregnant women seeking obstetrical care. The objective of this study was to compare the efficacy (virus load response), adverse events, and obstetrical and neonatal outcomes of three different regimens of cART in HIV-infected pregnant women initiating treatment in Rio de Janeiro, Brazil. This was a retrospective cohort study of cART-naive pregnant women who initiated either ritonavir-boosted protease inhibitors (atazanavir or lopinavir), efavirenz, or raltegravir plus a backbone regimen. From 2014 to 2018, 390 pregnant women were followed over time. At baseline, the median viral load (VL) for HIV was 4.1 log copies/ml. Among participants who received cART for 2 to 7 weeks, the VL decline was greater for raltegravir (2.24 log copies/ml) than for efavirenz or protease inhibitors (P < 0.001). Virologic suppression was achieved in 87% of women on raltegravir near delivery versus 73% on efavirenz and 70% on protease inhibitors (P = 0.011). Patients on raltegravir achieved virologic suppression faster than those on other regimens (P = 0.019). Overall, the HIV perinatal infection rate was 1.5%. This clinical study compared three potent and well-tolerated cART regimens and demonstrated that a higher proportion of participants on raltegravir achieved an undetectable HIV VL near delivery (P = 0.011) compared to the other arms. These findings suggest that raltegravir-containing regimens are optimal regimens for women with HIV initiating treatment late in pregnancy.

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

BACKGROUND: Zika 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. OBJECTIVES: To 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 DESIGN: Laboratory 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. RESULTS: Of 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). CONCLUSIONS: Among 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.

Zika Virus Infection Associated With Congenital Birth Defects in a HIV-infected Pregnant Woman.

We describe a case of Zika virus infection acquired during the first trimester in a HIV-infected pregnant woman that led to multiple fetal malformations and fetal demise in Rio de Janeiro, Brazil.

[The Hospital Information System of the Brazilian Unified National Health System: a performance evaluation for auditing maternal near miss]. / Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH-SUS): uma avaliação do seu desempenho para a identificação do near miss materno.

This study aimed to investigate the performance of the Hospital Information System of the Brazilian Unified National Health System (SIH-SUS) in identifying cases of maternal near miss in a hospital in Rio de Janeiro, Brazil, in 2008. Cases were identified by reviewing medical records of pregnant and postpartum women admitted to the hospital. The search for potential near miss events in the SIH-SUS database relied on a list of procedures and codes from the International Classification of Diseases, 10th revision (ICD-10) that were consistent with this diagnosis. The patient chart review identified 27 cases, while 70 potential occurrences of near miss were detected in the SIH-SUS database. However, only 5 of 70 were "true cases" of near miss according to the chart review, which corresponds to a sensitivity of 18.5% (95%CI: 6.3-38.1), specificity of 94.3% (95%CI: 92.8-95.6), area under the ROC of 0.56 (95%CI: 0.48-0.63), and positive predictive value of 10.1% (IC95%: 4.7-20.3). These findings suggest that SIH-SUS does not appear appropriate for monitoring maternal near miss.

Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH-SUS): uma avaliação do seu desempenho para a identificação do near miss materno / The Hospital Information System of the Brazilian Unified National Health System: a performance evaluation for auditing maternal near miss / Sistema de Información Hospitalaria del Sistema Único de Salud (SIH-SUS): una evaluación de su rendimiento para la identificación de near miss materno

Este estudo avaliou o desempenho do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH-SUS) na identificação de casos de near miss materno ocorridos em hospital do Rio de Janeiro, em 2008. Os casos foram captados pela revisão de todos os prontuários médicos de gestantes ou puérperas internadas na unidade, e a busca por potenciais eventos de near miss na base do SIH-SUS valeu-se de uma lista de procedimentos e códigos da Classificação Internacional de Doenças, 10ª revisão (CID-10), que fossem compatíveis com esse diagnóstico. A revisão de prontuários identificou 27 casos, enquanto na base do SIH-SUS encontrou-se 70 possíveis ocorrências de near miss. Porém, dessas 70 apenas cinco efetivamente eram casos near miss conforme os prontuários, correspondendo então à sensibilidade de 18,5% (IC95%: 6,3-38,1), especificidade de 94,3% (IC95%: 92,8-95,6), área sob a curva ROC de 0,56 (IC95%: 0,48-0,63) e valor preditivo positivo de 10,1% (IC95%: 4,7-20,3). Esses achados sugerem que o SIH-SUS não é adequado para o monitoramento dos casos de near miss materno.

This study aimed to investigate the performance of the Hospital Information System of the Brazilian Unified National Health System (SIH-SUS) in identifying cases of maternal near miss in a hospital in Rio de Janeiro, Brazil, in 2008. Cases were identified by reviewing medical records of pregnant and postpartum women admitted to the hospital. The search for potential near miss events in the SIH-SUS database relied on a list of procedures and codes from the International Classification of Diseases, 10th revision (ICD-10) that were consistent with this diagnosis. The patient chart review identified 27 cases, while 70 potential occurrences of near miss were detected in the SIH-SUS database. However, only 5 of 70 were "true cases" of near miss according to the chart review, which corresponds to a sensitivity of 18.5% (95%CI: 6.3-38.1), specificity of 94.3% (95%CI: 92.8-95.6), area under the ROC of 0.56 (95%CI: 0.48-0.63), and positive predictive value of 10.1% (IC95%: 4.7-20.3). These findings suggest that SIH-SUS does not appear appropriate for monitoring maternal near miss.

Este estudio evaluó el desempeño del Sistema de Información Hospitalaria del Sistema Único de Salud (SIH-SUS) en la identificación de casos de near miss materno en un hospital de Río de Janeiro en 2008. Los casos se obtuvieron mediante revisión de los historiales clínicos de las embarazadas y puérperas ingresadas en la unidad, y la búsqueda de posibles eventos near miss en la base del SIH-SUS se basó en una lista de procedimientos y códigos de la Clasificación Internacional de Enfermedades (CIE-10) que son compatibles con este diagnóstico. Una revisión retrospectiva de historiales clínicos identificó 27 casos, mientras que la base de la SIH-SUS localizó 70 posibles casos con este diagnóstico. Sin embargo, sólo cinco de los 70 casos fueron en realidad casos de near miss, por ello, la sensibilidad correspondiente fue de un 18,5% (IC95%: 6,3-38,1), una especificidad del 94,3% (IC95%: 92,8-95,6), el área bajo la curva ROC de un 0,56 (IC95%: 0,48-0,63) y el valor predictivo positivo de un 10,1% (IC95%: 4,7-20,3). Estos hallazgos sugieren que SIH-SUS no es adecuado para el seguimiento de near miss.

Comparing different diagnostic approaches to severe maternal morbidity and near-miss: a pilot study in a Brazilian tertiary hospital.

OBJECTIVE: Despite recent guidelines proposed by the World Health Organization (WHO), the operational definition of maternal near-miss (MNM) is still heterogeneous. This study aimed at evaluating the pros and cons of three instruments in characterizing MNM cases. The performance of two of the three instruments was also investigated vis-à-vis the WHO criteria. STUDY DESIGN: A retrospective chart review study was carried out in a tertiary maternity hospital in Rio de Janeiro, Brazil. The medical records of 1163 obstetric hospital admissions from January to December 2008 were reviewed. Cases were first classified as 'positive' or otherwise according to the WHO, Waterstone and literature-based criteria. A descriptive analysis was then carried out focusing on divergent classifications. Finally, diagnostic properties of the Waterstone and the literature-based criteria were calculated taking the WHO criteria as reference standard. RESULTS: There were eight maternal deaths, 157 cases classified as 'positive' by at least one of the three approaches and 998 cases without severe morbidities. Twenty-seven cases of MNM were detected according to the WHO criteria, whereas the Waterstone and the literature-based criteria identified 123 and 153 cases, respectively. Among the 130 cases identified as 'negative' by the WHO criteria and 'positive' by the Waterstone or literature-based criteria, 119 presented hypertensive disorders (91.5%). Additionally, four cases were identified exclusively by the WHO criteria because of acute thrombocytopenia (platelets<50,000). Estimates of sensitivity, specificity, accuracy and negative predictive values were all above 75% for the Waterstone and literature-based approaches, but both criteria presented positive predictive values (PPV) below 60% even with high magnitudes of MNM. CONCLUSION: These results underline that different approaches entail heterogeneous estimates of MNM. The Waterstone and the literature-based criteria are not suitable for a definitive diagnosis of MNM in view of their low PPV, but they seem adequate as a first approach in investigating MNM. While negative results by both alternative criteria virtually rule out MNM, a positive result would require a reassessment using the WHO criteria to confirm the diagnosis of maternal near-miss.

Management of obstetric antiphospholipid syndrome.

Recurrent early miscarriages (excluding chromosomal anomalies), late fetal loss, and maternal thrombosis are characteristic of obstetric antiphospholipid syndrome (APS). Obstetric complications such as preeclampsia, fetal growth restriction, premature delivery, and fetal death also occur in higher frequency in APS patients than in the general population. A high-risk obstetric center is needed for proper evaluation of and intervention with pregnant women with APS. Association with lupus carries additional risk of thrombosis when antiphospholipid antibodies (aPLs) are present. Gestational results with live births are improved to about 80% when antithrombotic therapy is used, but failure in 20% to 30% of the cases despite correct treatment with low-dose aspirin with or without heparin reveals new pathways for pregnancy loss in APS and unmet needs. At the moment, there is no recommendation to investigate patients with infertility for the presence of aPLs.

Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor.

Glycyrrhizin (GL), an anti-inflammatory compound isolated from licorice (Glycyrrhiza glabra), has been previously identified as a thrombin inhibitor (Francischetti et al., Biochem Biophys Res Commun 1997;235:259-63). Here we report the in vivo effects of GL upon two experimental models of induced thrombosis in rats. Intravenous administration of GL caused a dose-dependent reduction in thrombus size on a venous thrombosis model that combines stasis and hypercoagulability. It was observed that GL doses of 180 mg/kg body weight produced 93% decrease on thrombus weight. This effect showed a time-dependent pattern being significantly reduced when the thrombogenic stimulus was applied 60 min after drug administration. GL was also able to prevent thrombosis using an arteriovenous shunt model. GL doses of 180 and 360 mg/kg decreased the thrombus weight by 35 and 90%, respectively. Accordingly, the APTT ex vivo was enhanced by 1.5- and 4.3-fold at GL doses of 180 and 360 mg/kg, respectively. In addition, GL doses above 90 mg/kg caused significant hemorrhagic effect. In contrast with heparin, GL did not potentiate the inhibitory activity of antithrombin III or heparin cofactor II towards thrombin. Altogether, data indicate that GL is an effective thrombin inhibitor in vivo, which may account for its other known pharmacological properties.