RESUMO
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.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Feminino , Gravidez , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/farmacologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/genética , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Antirretrovirais/uso terapêutico , Mutação , Genótipo , Farmacorresistência Viral/genéticaRESUMO
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.
Assuntos
Fármacos Anti-HIV , Ganho de Peso na Gestação , Infecções por HIV , Inibidores de Integrase de HIV , Integrase de HIV , Humanos , Feminino , Gravidez , Masculino , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Gestantes , Estudos Retrospectivos , Fármacos Anti-HIV/uso terapêutico , Aumento de Peso , Inibidores de Integrase de HIV/uso terapêutico , Resultado da GravidezRESUMO
OBJECTIVE: To assess in ART-naïve pregnant women randomized to efavirenz- versus raltegravir-based ART (IMPAACT P1081) whether pretreatment drug resistance (PDR) with minority frequency variants (<20% of individual's viral quasispecies) affects antiretroviral treatment (ART)-suppression at term. DESIGN: A 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. METHODS: HIV 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. RESULTS: PDR 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 (p<0.0001), a shorter duration of ART prior to delivery (p<0.0001), and randomization to efavirenz- (versus raltegravir-) based ART (p = 0.0085). CONCLUSIONS: We 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.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , HIV-1 , Alcinos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Benzoxazinas , Estudos de Casos e Controles , Ciclopropanos , Farmacorresistência Viral/genética , Feminino , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , Humanos , Preparações Farmacêuticas , Gravidez , Gestantes , RNA , Raltegravir Potássico/uso terapêutico , Carga ViralRESUMO
BACKGROUND: Integrase 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. SETTING: NICHD 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. METHODS: Two 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 <0.18 kg/wk and high as >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. RESULTS: Raltegravir-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. CONCLUSIONS: A 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.
Assuntos
Infecções por HIV , National Institute of Child Health and Human Development (U.S.) , Feminino , Gravidez , Humanos , Estados Unidos , Raltegravir Potássico/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase , Aumento de PesoRESUMO
BACKGROUND: The effect of pneumococcal vaccination of mothers with human immunodeficiency virus (HIV) on infant responses to childhood vaccination has not been studied. We compared the immunogenicity of 10-valent pneumococcus conjugate vaccine (PCV-10) in HIV-exposed uninfected infants born to mothers who received PCV-10, 23-valent pneumococcus polysaccharide vaccine (PPV-23), or placebo during pregnancy. METHODS: Antibody levels against 7 serotypes were measured at birth, before the first and second doses of PCV-10m and after completion of the 2-dose regimen in 347 infants, including 112 born to mothers who received PPV-23, 112 who received PCV-10, and 119 who received placebo during pregnancy. Seroprotection was defined by antibody levels ≥0.35 µg/mL. RESULTS: At birth and at 8 weeks of life, antibody levels were similar in infants born to PCV-10 or PPV-23 recipients and higher than in those born to placebo recipient. After the last dose of PCV-10, infants in the maternal PCV-10 group had significantly lower antibody levels against 5 serotypes than those in the maternal PPV-23 group and against 3 serotypes than those in the maternal placebo group, and they did not have higher antibody levels against any serotype. The seroprotection rate against 7 serotypes was 50% in infants in the maternal PCV-10 group, compared with 71% in both of the maternal PPV-23 and placebo groups (Pâ <â .001). CONCLUSIONS: Administration of PCV-10 during pregnancy was associated with decreased antibody responses to PCV-10 and seroprotection rates in infants. Considering that PCV-10 and PPV-23 had similar immunogenicity in pregnant women with HIV and that administration of PPV-23 did not affect the immunogenicity of PCV-10 in infants, PPV-23 in pregnancy may be preferred over PCV-10.
Assuntos
Infecções por HIV , Infecções Pneumocócicas , Anticorpos Antibacterianos/uso terapêutico , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Polissacarídeos , Gravidez , Streptococcus pneumoniae , Vacinação , Vacinas ConjugadasRESUMO
BACKGROUND: Pneumococcal vaccination is recommended in people with HIV, prioritizing PCV. We compared the immunogenicity of PCV-10 and PPV-23 administered antepartum or postpartum. METHODS: This double-blind study randomized 346 pregnant women with HIV on antiretrovirals to PCV-10, PPV-23, or placebo at 14-34 weeks gestational age. Women who received placebo antepartum were randomized at 24 weeks postpartum to PCV-10 or PPV-23. Antibodies against 7 serotypes common to both vaccines and 1 serotype only in PPV-23 were measured by ELISA/chemiluminescence; B- and T-cell responses to serotype 1 by FLUOROSPOT; and plasma cytokines/chemokines by chemiluminescence. RESULTS: Antibody responses were higher after postpartum versus antepartum vaccination. PCV-10 generated lower antibody levels than PPV-23 against 4 and higher against 1 of 7 common serotypes. Additional factors associated with high postvaccination antibody concentrations were high prevaccination antibody concentrations and CD4+ cells; low CD8+ cells and plasma HIV RNA; and several plasma cytokines/chemokines. Serotype 1 B- and T-cell memory did not increase after vaccination. CONCLUSIONS: Antepartum immunization generated suboptimal antibody responses, suggesting that postpartum booster doses may be beneficial and warrant further studies. Considering that PCV-10 and PPV-23 had similar immunogenicity, but PPV-23 covered more serotypes, use of PPV-23 may be prioritized in women with HIV on antiretroviral therapy. CLINICAL TRAILS REGISTRATION: NCT02717494.
Assuntos
Infecções por HIV , Infecções Pneumocócicas , Anticorpos Antibacterianos , Citocinas , Feminino , Infecções por HIV/complicações , Humanos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Polissacarídeos , Período Pós-Parto , Gravidez , Vacinação , Vacinas ConjugadasRESUMO
BACKGROUND: Pregnant 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). METHODS: This 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. RESULTS: A 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. CONCLUSIONS: Detectable VVL in pregnant women with undetectable/nonquantifiable PVL while receiving ART was rare and not associated with perinatal HIV transmission.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Vigna/virologia , Carga Viral/efeitos dos fármacos , Eliminação de Partículas Virais , Adulto , Alcinos/uso terapêutico , Benzoxazinas/uso terapêutico , Ciclopropanos/uso terapêutico , Farmacorresistência Viral , Feminino , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Lactente , Lamivudina/uso terapêutico , Gravidez , Gestantes , Raltegravir Potássico/uso terapêutico , Zidovudina/uso terapêuticoRESUMO
BACKGROUND: Pneumococcus remains an important cause of morbidity in pregnant women with HIV and their infants. We compared the safety and immunogenicity of PCV-10 and PPV-23 with placebo administered in pregnancy. METHODS: This double-blind, multicentre, randomised controlled trial was done at eight outpatient clinics in Brazil. Eligible participants were adult women with HIV who were pregnant at a gestational age between 14 weeks and less than 34 weeks and who were taking antiretroviral therapy at study entry. Participants were randomly assigned (1:1:1) to receive either PCV-10, PPV-23, or placebo. Participants and study teams were unaware of treatment allocation. Antibodies against seven vaccine serotypes in PCV-10 and PPV-23 were measured by ELISA. The primary outcomes were maternal and infant safety assessed by the frequency of adverse events of grade 3 or higher; maternal seroresponse (defined as ≥2-fold increase in antibodies from baseline to 28 days after immunisation) against five or more serotypes; and infant seroprotection (defined as anti-pneumococcus antibody concentration of ≥0·35 µg/mL) against five or more serotypes at 8 weeks of life. The study was powered to detect differences of 20% or higher in the primary immunological outcomes between treatment groups. This trial is registered with ClinicalTrials.gov, NCT02717494. FINDINGS: Between April 1, 2016, and Nov 30, 2017, we enrolled 347 pregnant women with HIV, of whom 116 were randomly assigned to the PCV-10 group, 115 to the PPV-23 group, and 116 to the placebo group. One participant in the PCV-10 group did not receive the vaccine and was excluded from subsequent analyses. The frequency of adverse events of grade 3 or higher during the first 4 weeks was similar in the vaccine and placebo groups (3% [90% CI 1-7] for the PCV-10 group, 2% [0-5] for the PPV-23 group, and 3% [1-8] for the placebo group). However, injection site and systemic grade 2 adverse reactions were reported more frequently during the first 4 weeks in the vaccine groups than in the placebo group (14% [9-20] for the PCV-10 group, 7% [4-12] for the PPV-23 group, and 3% [1-7] for the placebo group). The frequency of grade 3 or higher adverse effects was similar across maternal treatment groups (20% [14-27] for the PCV-10 group, 21% [14-28] for the PPV-23 group, and 20% [14-27] for the placebo group). Seroresponses against five or more serotypes were present in 74 (65%) of 114 women in the PCV-10 group, 72 (65%) of 110 women in the PPV-23 group, and none of the 113 women in the placebo group at 4 weeks post vaccination (p<0·0001 for PPV-23 group vs placebo and PCV-10 group vs placebo). Seroresponse differences of 20% or higher in vaccine compared with placebo recipients persisted up to 24 weeks post partum. At birth, 76 (67%) of 113 infants in the PCV-10 group, 62 (57%) of 109 infants in the PPV-23 group, and 19 (17%) of 115 infants in the placebo group had seroprotection against five or more serotypes (p<0·0001 for PPV-23 vs placebo and PCV-10 vs placebo). At 8 weeks, the outcome was met by 20 (19%) of 108 infants in the PCV-10 group, 24 (23%) of 104 infants in the PPV-23 group, and one (1%) of 109 infants in the placebo group (p<0·0001). Although a difference of 20% or higher compared with placebo was observed only in the infants who received PPV-23 at 8 weeks of life, the difference between the two vaccine groups was not appreciable. INTERPRETATION: PCV-10 and PPV-23 were equally safe and immunogenic in pregnant women with HIV and conferred similar levels of seroprotection to their infants. In areas in which childhood PCV administration decreased the circulation of PCV serotypes, PPV-23 administration to pregnant women with HIV might be more advantageous than PCV by virtue of including a broader range of serotypes. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.
Assuntos
Anticorpos Antibacterianos/imunologia , Infecções por HIV/complicações , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Adulto , Fármacos Anti-HIV/uso terapêutico , Brasil , Método Duplo-Cego , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Lactente , Recém-Nascido , Masculino , Placenta/imunologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/efeitos adversos , Gravidez , Gestantes , Streptococcus pneumoniae/imunologia , Adulto JovemRESUMO
BACKGROUND: Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy. METHODS: An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20-<37 weeks gestation) living with HIV were assigned to antiretroviral regimens containing either raltegravir (400 mg twice daily) or efavirenz (600 mg each night) plus lamivudine 150 mg and zidovudine 300 mg twice daily (or approved alternative backbone regimen), using a web-based, permuted-block randomisation stratified by gestational age and backbone regimen. The primary efficacy outcome was plasma HIV viral load below 200 copies per mL at (or near) delivery. The primary efficacy analysis included all women with a viral load measurement at (or near) delivery who had viral load of at least 200 copies per mL before treatment and no genotypic resistance to any study drugs; secondary analyses eliminated these exclusion criteria. The primary safety analyses included all women who received study drug, and their infants. This trial is registered with Clinicaltrials.gov, number NCT01618305. FINDINGS: From Sep 5, 2013, to Dec 11, 2018, 408 women were enrolled (206 raltegravir, 202 efavirenz) and 394 delivered on-study (200 raltegravir, 194 efavirenz); 307 were included in the primary efficacy analysis (153 raltegravir, 154 efavirenz). 144 (94%) women in the raltegravir group and 129 (84%) in the efavirenz group met the primary efficacy outcome (absolute difference 10%, 95% CI 3-18; p=0·0015); the difference primarily occurred among women enrolling later in pregnancy (interaction p=0·040). Frequencies of severe or life-threatening adverse events were similar among mothers (30% in each group; 61 raltegravir, 59 efavirenz) and infants (25% in each group; 50 raltegravir, 48 efavirenz), with no treatment-related deaths. INTERPRETATION: Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Raltegravir Potássico/uso terapêutico , Adulto , Alcinos , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Ciclopropanos , Quimioterapia Combinada , Feminino , Infecções por HIV/prevenção & controle , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Lamivudina/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Raltegravir Potássico/efeitos adversos , Carga Viral/efeitos dos fármacos , Adulto Jovem , Zidovudina/uso terapêuticoRESUMO
The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. The target amprenavir area under the concentration-versus-time curve (AUC) was higher than the 10th percentile (27.7 µg · h/ml) of the median area under the curve for ritonavir-boosted fosamprenavir in adults receiving twice-daily fosamprenavir-ritonavir at 700 mg/100 mg. Twenty-nine women were included in the analysis. The amprenavir AUC from time zero to 12 h (AUC0-12) was lower (geometric mean ratio [GMR], 0.60 [confidence interval {CI}, 0.49 to 0.72] [P < 0.001]) while its apparent oral clearance was higher (GMR, 1.68 [CI, 1.38 to 2.03] [P < 0.001]) in the third trimester than postpartum. Similarly, the ritonavir AUC0-12 was lower in the second (GMR, 0.51 [CI, 0.28 to 0.91] [P = 0.09]) and third (GMR, 0.72 [CI, 0.55 to 0.95] [P = 0.005]) trimesters than postpartum, while its apparent oral clearance was higher in the second (GMR, 1.98 [CI, 1.10 to 3.56] [P = 0.06]) and third (GMR, 1.38 [CI, 1.05 to 1.82] [P = 0.009]) trimesters than postpartum. The amprenavir area under the curve exceeded the target for 6/8 (75%) women in the 2nd trimester, 18/28 (64%) in the 3rd trimester, and 19/22 (86.4%) postpartum, and the trough concentrations (Cmin) of amprenavir were 4- to 16-fold above the mean amprenavir-protein-adjusted 50% inhibitory concentration (IC50) of 0.146 µg/ml. Although amprenavir plasma concentrations in women receiving ritonavir-boosted fosamprenavir were lower during pregnancy than postpartum, the reduced amprenavir concentrations were still above the exposures needed for viral suppression.
Assuntos
Carbamatos/farmacocinética , Furanos/farmacocinética , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacocinética , Complicações Infecciosas na Gravidez/tratamento farmacológico , Ritonavir/farmacocinética , Sulfonamidas/farmacocinética , Adulto , Área Sob a Curva , Carbamatos/efeitos adversos , Feminino , Furanos/efeitos adversos , Inibidores da Protease de HIV/efeitos adversos , Humanos , Idade Materna , Gravidez , Trimestres da Gravidez , RNA Viral/sangue , Ritonavir/efeitos adversos , Sulfonamidas/efeitos adversos , Carga ViralRESUMO
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.
Assuntos
Coinfecção/epidemiologia , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/etiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia , Adulto , Algoritmos , Brasil/epidemiologia , Sistema Nervoso Central/anormalidades , Febre de Chikungunya/complicações , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Estudos de Coortes , Coinfecção/diagnóstico , Dengue/complicações , Dengue/diagnóstico , Dengue/epidemiologia , Surtos de Doenças , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Resultado da Gravidez , Prevalência , Fatores de Risco , Adulto Jovem , Infecção por Zika virus/diagnósticoRESUMO
BACKGROUND: HIV-exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial. METHODS: Infectious morbidity, mortality and undernutrition were evaluated within a cohort of 1000 HEU infants enrolled between April 2004 and April 2010 in Brazil (n = 766) and South Africa (n = 234) as part of the NICHD/HPTN 040 trial of 3 different antiretroviral regimens to decrease intrapartum HIV vertical transmission. RESULTS: Twenty-three percent of infants had at least 1 infectious serious adverse effect. Infants born to mothers with <12 years of education [adjusted odds ratio (AOR), 2.6; 95% confidence interval [CI], 1.2-5.9), with maternal viral load of >1,000,000 copies/mL at delivery (AOR, 9.9; 95% CI, 1.6-63.1) were more likely to have infectious serious adverse effects. At 6 months, the infant mortality rate per 1000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 month of age with 18% having a weight-for-age Z score ≤-2, and 22% with height for Z score ≤-2. The likelihood of infant mortality was greater among infants born in South Africa compared with Brazil (AOR, 6.2; 95% CI, 2.5-15.8), high maternal viral load (AOR, 1.7; 95% CI, 1.01-2.9) and birth weight-for-age Z score ≤-2 (AOR, 5.2; 95% CI, 1.8-14.8). CONCLUSIONS: There were high rates of undernutrition, stunting and infectious serious adverse effect in this study's formula-fed HEU population. Suppressing maternal HIV viral load during the peripartum period may be a modifiable risk factor to decrease infant mortality.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , Mortalidade Infantil , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Brasil/epidemiologia , Causas de Morte , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Humanos , Lactente , Fórmulas Infantis , Masculino , Desnutrição/epidemiologia , Desnutrição/etiologia , Estado Nutricional , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/mortalidade , Fatores de Risco , África do Sul/epidemiologia , Carga ViralRESUMO
Background: The presence of antiretroviral drug-associated resistance mutations (DRMs) may be particularly problematic in human immunodeficiency virus (HIV)-infected pregnant women as it can lead to mother-to-child transmission (MTCT) of resistant HIV strains. This study evaluated the prevalence and the effect of antiretroviral DRMs in previously untreated mother-infant pairs. Methods: A case-control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate DRMs as a predictor of HIV MTCT in specimens obtained from mother-infant pairs. ViroSeq HIV-1 genotyping was performed on mother-infant specimens to assess for clinically relevant DRMs. Results: One hundred forty infants acquired HIV infection; of these, 123 mother-infant pairs (88%) had specimens successfully amplified using ViroSeq and assessed for drug resistance genotyping. Additionally, 483 of 560 (86%) women who did not transmit HIV to infants also had samples evaluated for DRMs. Sixty-three of 606 (10%) women had clinically relevant DRMs; 12 (2%) had DRMs against >1 drug class. Among 123 HIV-infected infants, 13 (11%) had clinically relevant DRMs, with 3 (2%) harboring DRMs against >1 drug class. In univariate and multivariate analyses, DRMs in mothers were not associated with increased HIV MTCT (adjusted odds ratio, 0.8 [95% confidence interval, .4-1.5]). Presence of DRMs in transmitting mothers was strongly associated with DRM presence in their infants (P < .001). Conclusions: Preexisting DRMs were common in untreated HIV-infected pregnant women, but did not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed, they may transmit resistant mutations, thus complicating infant management.
Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral Múltipla , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Transmissão Vertical de Doenças Infecciosas , Adolescente , Adulto , Fármacos Anti-HIV/classificação , Feminino , Infecções por HIV/transmissão , HIV-1/genética , Humanos , Lactente , Mutação , Gravidez , Adulto JovemRESUMO
OBJECTIVE: There are limited data regarding Xpert performance to detect Group B Streptococcus (GBS) in HIV-infected pregnant women. We evaluated the accuracy of a rapid real-time polymerase chain reaction (PCR) test in a cohort of HIV-infected women. METHODS: At 35-37 weeks of pregnancy, a pair of combined rectovaginal swabs were collected for two GBS assays in a cohort of sequentially included HIV-infected women in Rio de Janeiro: (1) culture; and (2) real-time PCR assay [GeneXpert GBS (Cepheid, Sunnyvale, CA)]. Using culture as the reference, sensitivity, specificity, positive and negative-likelihood ratios were estimated. RESULTS: From June 2012 to February 2015, 337 pregnant women met inclusion criteria. One woman was later excluded, due to failure to obtain a result in the index test; 336 were included in the analyses. The GBS colonization rate was 19.04%. Sensitivity and specificity of the GeneXpert GBS assay were 85.94% (95% CI: 75.38-92.42) and 94.85% (95% CI: 91.55-96.91), respectively. Positive and negative predictive values were 79.71% (95% CI: 68.78-87.51) and 96.63% (95% CI: 93.72-98.22), respectively. CONCLUSIONS: GeneXpert GBS is an acceptable test for the identification of GBS colonization in HIV-infected pregnant women and represents a reasonable option to detect GBS colonization in settings where culture is not feasible.
Assuntos
Complicações Infecciosas na Gravidez/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/isolamento & purificação , Adulto , Feminino , Infecções por HIV/complicações , Humanos , Transmissão Vertical de Doenças Infecciosas , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Estudos Prospectivos , Infecções Estreptocócicas/complicações , Streptococcus agalactiae/genética , Fatores de Tempo , Vagina/microbiologia , Carga Viral/estatística & dados numéricos , Adulto JovemAssuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/sangue , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Período Pós-Parto/sangue , Complicações Infecciosas na Gravidez/sangue , Terceiro Trimestre da Gravidez/sangue , Carga Viral , Adulto , Cesárea , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológicoRESUMO
BACKGROUND: The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. METHODS: Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. RESULTS: A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups). CONCLUSIONS: In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.).
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/prevenção & controle , HIV-1 , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Lamivudina/uso terapêutico , Nelfinavir/uso terapêutico , Nevirapina/uso terapêutico , Zidovudina/uso terapêutico , Antirretrovirais/efeitos adversos , Farmacorresistência Viral , Quimioterapia Combinada/efeitos adversos , Feminino , Infecções por HIV/mortalidade , Infecções por HIV/transmissão , Humanos , Fórmulas Infantis , Recém-Nascido , Estimativa de Kaplan-Meier , Lamivudina/efeitos adversos , Masculino , Nelfinavir/efeitos adversos , Nevirapina/efeitos adversos , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez , Zidovudina/efeitos adversosRESUMO
Group B Streptococcus (GBS) is a leading cause of infectious morbidity in newborns. We describe the prevalence of GBS colonization and the serotypes and antibiotic susceptibility profiles of isolates obtained from a cohort of human immunodeficiency virus (HIV)-infected pregnant women. This was a cross-sectional study at a centre for the prevention of mother-to-child transmission of HIV. Vaginal and rectal swabs were collected at 35-37 weeks of gestation from 158 eligible women. GBS isolates were serotyped and antimicrobial susceptibility tests performed. Patient sociodemographic characteristics, CD4 counts and viral loads were abstracted from records. The overall anogenital prevalence of GBS colonization was 49/158 (31.0%): 40/158 (25.3%) for vagina, 19/158 (12.0%) for rectum and 10/158 (6.3%) for both. Predominant serotypes were Ib (34.9%) and Ia (25.6%). All were penicillin-susceptible. Two were resistant to erythromycin (4.0%) and one to clindamycin (2.0%). The colonization rate by GBS was high in this cohort. Serotype Ib was the most frequently identified.
Assuntos
Infecções por HIV/complicações , Complicações Infecciosas na Gravidez/microbiologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/efeitos dos fármacos , Adulto , Antibacterianos/farmacologia , Contagem de Linfócito CD4 , Clindamicina/farmacologia , Estudos Transversais , Farmacorresistência Bacteriana , Eritromicina/farmacologia , Feminino , Humanos , Lactente , Recém-Nascido , Testes de Sensibilidade Microbiana , Penicilinas/farmacologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Prevalência , Reto/microbiologia , Sorotipagem , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/isolamento & purificação , Vagina/microbiologia , Carga ViralRESUMO
The goal of this study was to evaluate changes in plasma human immunodeficiency virus (HIV) RNA concentration [viral load (VL)] and CD4+ percentage (CD4%) during 6-12 weeks postpartum (PP) among HIV-infected women and to assess differences according to the reason for receipt of antiretrovirals (ARVs) during pregnancy [prophylaxis (PR) vs. treatment (TR)]. Data from a prospective cohort of HIV-infected pregnant women (National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study) were analyzed. Women experiencing their first pregnancy who received ARVs for PR (started during pregnancy, stopped PP) or for TR (initiated prior to pregnancy and/or continued PP) were included and were followed PP. Increases in plasma VL (> 0.5 log10) and decreases in CD4% (> 20% relative decrease in CD4%) between hospital discharge (HD) and PP were assessed. Of the 1,229 women enrolled, 1,119 met the inclusion criteria (PR: 601; TR: 518). At enrollment, 87% were asymptomatic. The median CD4% values were: HD [34% (PR); 25% (TR)] and PP [29% (PR); 24% (TR)]. The VL increases were 60% (PR) and 19% (TR) (p < 0.0001). The CD4% decreases were 36% (PR) and 18% (TR) (p < 0.0001). Women receiving PR were more likely to exhibit an increase in VL [adjusted odds ratio (AOR) 7.7 (95% CI: 5.5-10.9) and a CD4% decrease (AOR 2.3; 95% CI: 1.6-3.2). Women receiving PR are more likely to have VL increases and CD4% decreases compared to those receiving TR. The clinical implications of these VL and CD4% changes remain to be explored.
Assuntos
Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Infecções por HIV/virologia , Complicações Infecciosas na Gravidez/virologia , Carga Viral , Adulto , Região do Caribe , Estudos de Coortes , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , América Latina , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Prospectivos , RNA ViralRESUMO
The goal of this study was to evaluate changes in plasma human immunodeficiency virus (HIV) RNA concentration [viral load (VL)] and CD4+ percentage (CD4 percent) during 6-12 weeks postpartum (PP) among HIV-infected women and to assess differences according to the reason for receipt of antiretrovirals (ARVs) during pregnancy [prophylaxis (PR) vs. treatment (TR)]. Data from a prospective cohort of HIV-infected pregnant women (National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study) were analyzed. Women experiencing their first pregnancy who received ARVs for PR (started during pregnancy, stopped PP) or for TR (initiated prior to pregnancy and/or continued PP) were included and were followed PP. Increases in plasma VL (> 0.5 log10) and decreases in CD4 percent (> 20 percent relative decrease in CD4 percent) between hospital discharge (HD) and PP were assessed. Of the 1,229 women enrolled, 1,119 met the inclusion criteria (PR: 601; TR: 518). At enrollment, 87 percent were asymptomatic. The median CD4 percent values were: HD [34 percent (PR); 25 percent (TR)] and PP [29 percent (PR); 24 percent (TR)]. The VL increases were 60 percent (PR) and 19 percent (TR) (p < 0.0001). The CD4 percent decreases were 36 percent (PR) and 18 percent (TR) (p < 0.0001). Women receiving PR were more likely to exhibit an increase in VL [adjusted odds ratio (AOR) 7.7 (95 percent CI: 5.5-10.9) and a CD4 percent decrease (AOR 2.3; 95 percent CI: 1.6-3.2). Women receiving PR are more likely to have VL increases and CD4 percent decreases compared to those receiving TR. The clinical implications of these VL and CD4 percent changes remain to be explored.