Retrospective analysis of risk factors and gaps in prevention strategies for mother-to-child HIV transmission in Rio de Janeiro, Brazil

Background Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15–24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. Methods We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. Results We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT cascade, the sequential steps of PMTCT interventions, we found inadequate retention in care among both cases and controls, and cases were significantly less likely than controls to continue receiving care throughout the cascade (p < 0.05). Motives for incompletion of PMTCT measures included infrastructural issues, such as HIV test results not being returned, but were most often due to lack of care-seeking. Over the course of the study period, PMTCT completion improved, although it remained below the 95% target for antenatal care, HIV testing, and antenatal ART set by the WHO. Adding concern, evaluation of co-infections indicated that case infants were also more likely to have congenital syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). Conclusions While PMTCT coverage has improved over the years, completion of services remains insufficient. Along with interventions to promote care-seeking behaviour, increased infrastructural support for PMTCT services is needed to meet the HIV MTCT elimination goal in Brazil as well as address rising national rates of congenital syphilis

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec

Neutralization of primary HIV-1 isolated from individuals residing in Rio de Janeiro

HEC/FIOCRUZ AIDS Clinical Research Group: S Cavalcante, MCG Galhardo, MRC Guimarães, VC Rolla, VG Veloso.Submitted by Fábio Marques ([email protected]) on 2019-02-11T18:27:54Z No. of bitstreams: 1 Neutralization_Beatriz_Grinsztejn_etal_INI_1996.pdf: 62065 bytes, checksum: 040632517254d67b67b8cbad268d14f8 (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2019-02-14T16:04:40Z (GMT) No. of bitstreams: 1 Neutralization_Beatriz_Grinsztejn_etal_INI_1996.pdf: 62065 bytes, checksum: 040632517254d67b67b8cbad268d14f8 (MD5)Made available in DSpace on 2019-02-14T16:04:40Z (GMT). No. of bitstreams: 1 Neutralization_Beatriz_Grinsztejn_etal_INI_1996.pdf: 62065 bytes, checksum: 040632517254d67b67b8cbad268d14f8 (MD5) Previous issue date: 1996WHO/GPA/VDU, UNDP/World Bank, PIAF/Brazilian Ministry of Health DST/AIDS and CNPq.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Hospital dos Servidores do Estado do Rio de Janeiro. Rio de Janeiro, RJ, BrasilHospital Geral de Nova Iguaçu. Nova Iguaçu, RJ, Brasil

Diagnostic de la mycobacteriose generalisee: essai d'une methode simple et bon marche utilisable dans les pays en developpement

Submitted by Fábio Marques ([email protected]) on 2019-02-11T17:07:58Z No. of bitstreams: 1 Diagnosis of disseminated_Beatriz_Grinsztejn_etal_INI_1997.pdf: 781501 bytes, checksum: f96dc2d85a59c3a197607c4268879d72 (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2019-02-14T15:05:37Z (GMT) No. of bitstreams: 1 Diagnosis of disseminated_Beatriz_Grinsztejn_etal_INI_1997.pdf: 781501 bytes, checksum: f96dc2d85a59c3a197607c4268879d72 (MD5)Made available in DSpace on 2019-02-14T15:05:37Z (GMT). No. of bitstreams: 1 Diagnosis of disseminated_Beatriz_Grinsztejn_etal_INI_1997.pdf: 781501 bytes, checksum: f96dc2d85a59c3a197607c4268879d72 (MD5) Previous issue date: 1997Fundação Oswaldo Cruz. Instituto de Produtos Imunobiológicos. Departamento de Desenvolvimento Tecnológico./ Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Bacteriologia e Bioensaios. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas./ Universidade Federal do Rio de Janeiro. Instituto de Pneumologia e Fisiologia. Rio de Janeiro, RJ, Brasil.Hospital dos Servidores do Estado do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Departamento de Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Microbiologia Médica. Rio de Janeiro, RJ, Brasil.Avec le developpement de l'6pid6mie de syndrome d'immunod6ficience acquise (SIDA), l'isolement des mycobact6ries dans le sang est devenu un probleme fr6quent pour les laboratoires d'analyses m6dicales. Deux methodes ont et6 utilisees dans la presente 6tude pour cultiver les mycobact6ries a partir des pr6levements de sang pratiqu6s chez les patients atteints de SIDA: 1) inoculation directe d'un milieu biphasique, et 2) m6thode non commercialis6e par lyse et centrifugation. Au total, trois 6chantillons de sang consecutifs ont ete pr6leves a 15 minutes d'intervalle chez chacun des 50 patients pr6sum6s cliniquement atteints de mycobact6riose gen6ralisee. Les mycobacteries ont cultive pour 70 des 138 prelevements de sang realis6s chez 30 patients (soit 60%). Ces cultures ont permis d'obtenir Mycobacterium tuberculosis chez 19 patients (soit 63%), et des germes appartenant au complexe Mycobacterium avium chez 1 1 patients (soit 37%). Les cultures obtenues par lyse-centrifugation etaient positives chez 54% des patients, tandis que les cultures sur milieu biphasique 6taient positives chez 44% des patients (p > 0,05). Le nombre de cultures positives pour le complexe M. avium 6tait plus grand avec la lyse-centrifugation (91%) qu'avec le milieu biphasique (45,4%) (p < 0,05). Pour M. tuberculosis, la sensibilit6 de la lysecentrifugation (89,5%) et celle de l'inoculation directe en milieu biphasique (100%) 6taient toutefois comparables (p > 0,05). La lyse-centrifugation non commercialisee est une technique bon marche, fiable, et qui peut etre utilis6e comme m6thode de remplacement pour le diagnostic de la mycobact6ri6mie dans les pays en developpement.With the development of the acquired immunodeficiency syndrome (AIDS) epidemic, the isolation of mycobacteria from blood has become a common problem for clinical laboratories. In this study two methods were used for the recovery of mycobacteria from blood specimens obtained from AIDS patients: (1) direct inoculation of a biphasic medium, and (2) a non-commercial lysis-centrifugation method. A total of 3 consecutive blood samples were taken at 15-minute intervals from each of 50 AIDS patients with clinical suspicion of disseminated mycobacterial disease. Mycobacterium growth was noted in 70/138 blood specimens from 30 (60%) patients. These cultures yielded Mycobacterium tuberculosis in 19 (63%) and Mycobacterium avium complex organisms in 11 (37%) patients. Cultures using the lysis-centrifugation method were positive in 54% of the patients while cultures using biphasic medium were positive in 44% (P > 0.05). The positivity for M. avium complex was higher with lysis-centrifugation (91%) than with biphasic medium (45.4%) (P 0.05). The use of a non-commercial lysis-centrifugation technique is inexpensive, reliable, and can be an alternative method for the diagnosis of mycobacteraemia in developing countries

Assessment of minority frequency pretreatment HIV drug-resistant variants in pregnant women and associations with virologic non-suppression at term.

ObjectiveTo assess in ART-naïve pregnant women randomized to efavirenz- versus raltegravir-based ART (IMPAACT P1081) whether pretreatment drug resistance (PDR) with minority frequency variants (DesignA case-control study design compared PDR minority variants in cases with virologic non-suppression (plasma HIV RNA >200 copies/mL) at delivery to randomly selected ART-suppressed controls.MethodsHIV pol genotypes were derived from pretreatment plasma specimens by Illumina sequencing. Resistance mutations were assessed using the HIV Stanford Database, and the proportion of cases versus controls with PDR to their ART regimens was compared.ResultsPDR was observed in 7 participants (11.3%; 95% CI 4.7, 21.9) and did not differ between 21 cases and 41 controls (4.8% vs 14.6%, p = 0.4061). PDR detected only as minority variants was less common (3.2%; 95% CI 0.2, 11.7) and also did not differ between groups (0% vs. 4.9%; p = 0.5447). Cases' median plasma HIV RNA at delivery was 347c/mL, with most (n = 19/22) showing progressive diminution of viral load but not ≤200c/mL. Among cases with viral rebound (n = 3/22), none had PDR detected. Virologic non-suppression at term was associated with higher plasma HIV RNA at study entry (pConclusionsWe observed a moderate frequency of PDR that did not significantly contribute to virologic non-suppression at term. Rather, higher pretreatment plasma HIV RNA, randomization to efavirenz-based ART, and shorter duration of ART were associated with non-suppression. These findings support early prenatal care engagement of pregnant women and initiation of integrase inhibitor-based ART due to its association with more rapid suppression of plasma RNA levels. Furthermore, because minority variants appeared infrequent in ART-naïve pregnant women and inconsequential to ART-suppression, testing for minority variants may be unwarranted

Brief Report: Vaginal Viral Shedding With Undetectable Plasma HIV Viral Load in Pregnant Women Receiving 2 Different Antiretroviral Regimens: A Randomized Clinical Trial.

BackgroundPregnant women using antiretrovirals (ARVs) may have persistent vaginal viral shedding, which could be associated with sexual and perinatal HIV transmission. However, there are scant data on vaginal viral load (VVL) in pregnant women with undetectable plasma viral load (PVL).MethodsThis study was a post hoc analysis of an open-label randomized trial to evaluate the virologic response of 2 ART regimens. The participants were ART-naive women living with HIV initiating ART regimens between 20 and 36 weeks of pregnancy recruited at 19 clinical sites in 6 countries. Participants were randomized to receive 400 mg of raltegravir 2 times a day or 600 mg of efavirenz 4 times a day in addition to 150 mg of lamivudine and 300 mg of zidovudine 2 times a day. VVL and PVL tests were performed at every study visit. The primary outcome measures were HIV-1 PVL and VVL at maternal study week 4 and rates of perinatal HIV transmission.ResultsA total of 408 were enrolled, of whom 323 had VVL samples 4 weeks after enrollment and were included in this analysis. Among women with undetectable/nonquantifiable PVL during ART, the overall rate of quantifiable VVL at week 4 was 2.54% (7/275). Of the 275 with nonquantifiable PVL, 99.1% (115/116) and 96.2% (153/159) had nonquantifiable VVL in the efavirenz and raltegravir arms, respectively. None of the 7 women with quantifiable VVL at the week 4 study visit transmitted HIV to their infants.ConclusionsDetectable VVL in pregnant women with undetectable/nonquantifiable PVL while receiving ART was rare and not associated with perinatal HIV transmission

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

Effects of Initiating Raltegravir-Based Versus Efavirenz-Based Antiretroviral Regimens During Pregnancy on Weight Changes and Perinatal Outcomes: NICHD P1081

BackgroundIntegrase inhibitors have been associated with excess gestational weight gain that may lead to adverse pregnancy outcomes (APOs). This post hoc analysis of NICHD P1081 compared antepartum changes in weight and body mass index (BMI) in pregnant women initiating raltegravir- or efavirenz-based combined antiretroviral therapy (cART) and examined associations between rates of weight gain and APOs.SettingNICHD P1081 enrolled antiretroviral-naive pregnant women living with HIV in the second and third trimester in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States.MethodsTwo hundred eighty-one women enrolled between 20 and 31 gestational weeks were randomized to raltegravir- or efavirenz-based cART and followed for ≥4 weeks. A low rate of weight gain was defined as &lt;0.18 kg/wk and high as &gt;0.59 kg/wk. We compared weight gain and BMI increase between treatment arms using Kruskal-Wallis tests. Logistic regression was used to investigate the association between weight gain and APOs.ResultsRaltegravir-based cART was associated with significantly higher antepartum weight gain (median 0.36 kg/wk versus 0.29 kg/wk, P = 0.01) and BMI increase (median 0.14 kg/m 2 /wk versus 0.11 kg/m 2 /wk, P = 0.01) compared with efavirenz-based treatment. Women on raltegravir had less low weight gain (18% versus 36%) and more high weight gain (21% versus 12%) ( P = 0.001). Women with low weight gain were more likely than those with normal weight gain to have small for gestational age infants or a composite of APOs.ConclusionsA raltegravir-based antiretroviral regimen was associated with significantly higher antepartum rate of weight gain and BMI increase compared with efavirenz-based treatment in antiretroviral-naive pregnant women

Algorithm for diagnostic tests in symptomatic and asymptomatic pregnant women.

<p>Algorithm for diagnostic tests in symptomatic and asymptomatic pregnant women.</p