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INTRODUCTION: Antiretroviral therapy (ART) is very effective in preventing vertical transmission of HIV but some women on ART experience different virologic, immunologic, and safety profiles. While most pregnant women are closely monitored for short-term effects of ART during pregnancy, few women receive similar attention beyond pregnancy. We aimed to assess retention in care and clinical and laboratory-confirmed outcomes over 3 years after starting ART under Malawi's Option B + program. METHODS: We conducted a prospective cohort study of pregnant women newly diagnosed with HIV who started tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/3TC/EFV) for the first time at Bwaila Hospital in Lilongwe, Malawi between May 2015 and June 2016. Participants were followed for 3 years. We summarized demographic characteristics, pregnancy outcomes, and clinical and laboratory adverse events findings using proportions. Log-binomial regression models were used to estimate the overall risk ratios (RR) and the corresponding 95% confidence interval (CI) for the association between index pregnancy (i.e. index pregnancy vs. subsequent pregnancy) and preterm birth, and index pregnancy and low birthweight. RESULTS: Of the 299 pregnant women who were enrolled in the study, 255 (85.3%) were retained in care. There were 340 total pregnancies with known outcomes during the 36-month study period, 280 index pregnancies, and 60 subsequent pregnancies. The risks of delivering preterm (9.5% for index pregnancy and13.5% for subsequent pregnancy: RR = 0.70; 95% CI: 0.32-1.54), or low birth weight infant (9.8% for index pregnancy and 4.2% for subsequent pregnancy: RR = 2.36; 95% CI: 0.58-9.66) were similar between index and subsequent pregnancies. Perinatally acquired HIV was diagnosed in 6 (2.3%) infants from index pregnancies and none from subsequent pregnancies. A total of 50 (16.7%) women had at least one new clinical adverse event and 109 (36.5%) women had at least one incident abnormal laboratory finding. Twenty-two (7.3%) women switched to second line ART: of these 64.7% (8/17) had suppressed viral load and 54.9% (6/17) had undetectable viral load at 36 months. CONCLUSION: Most of the women who started TDF/3TC/EFV were retained in care and few infants were diagnosed with perinatally acquired HIV. Despite switching, women who switched to second line therapy continued to have higher viral loads suggesting that additional factors beyond TDF/3TC/EFV failure may have contributed to the switch. Ongoing support during the postpartum period is necessary to ensure retention in care and prevention of vertical transmission.
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Infecções por HIV , Nascimento Prematuro , Recém-Nascido , Gravidez , Lactente , Feminino , Humanos , Masculino , Malaui , Estudos Prospectivos , TenofovirRESUMO
BACKGROUND: Option B+ has increased the number of pregnant women initiating antiretroviral therapy for HIV, yet retention in HIV care is sub-optimal. Retention may be affected by antenatal depression. However, few data exist on antenatal depression in this population. AIM: Describe the prevalence and factors associated with antenatal depression among Malawian women enrolled in Option B+. METHOD: At their first antenatal visit, women with HIV provided demographic and psychosocial information, including depression as measured with the locally validated Edinburgh Postnatal Depression Scale (EPDS). Prevalence ratios (PR) for factors associated with probable depression (EPDS ≥6) were estimated with log binomial regression. RESULTS: 9.5% (95% CI: 7.5-11.9%) of women screened positive for current depression, and 46% self-reported a history of depression or anxiety. Women were more likely to screen positive for current depression if they reported a history of depression (adjusted PR: 2.42; 95% CI: 1.48-3.95) or had ever experienced intimate partner violence (1.77; 1.11-2.81). Having an unintended current pregnancy (1.78; 0.99-3.21), being unmarried (1.66; 0.97-2.84), or employed (1.56; 1.00-2.44) had potential associations with probable depression. CONCLUSIONS: Probable antenatal depression affected a notable proportion of women living with HIV, comparable to other global regions. Screening for antenatal depression in HIV care should be considered.
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Depressão/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Complicações na Gravidez/epidemiologia , Adulto , Estudos Transversais , Depressão/complicações , Feminino , Infecções por HIV/complicações , Humanos , Malaui , Gravidez , Cuidado Pré-Natal , Prevalência , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 µmol/liter (95% CI, 30 to 45 µmol/liter) by day 7 and by 49 µmol/liter (95% CI, 35 to 64µmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 µmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.
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Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Cryptococcus neoformans/efeitos dos fármacos , Ácido Desoxicólico/administração & dosagem , Infecções por HIV/virologia , Quimioterapia de Indução/métodos , Meningite Criptocócica/tratamento farmacológico , Adulto , Anfotericina B/toxicidade , Anemia/etiologia , Anemia/patologia , Antifúngicos/toxicidade , Contagem de Células Sanguíneas , Coinfecção , Creatinina/sangue , Cryptococcus neoformans/crescimento & desenvolvimento , Ácido Desoxicólico/toxicidade , Combinação de Medicamentos , Feminino , Flucitosina/uso terapêutico , HIV/isolamento & purificação , Infecções por HIV/mortalidade , Infecções por HIV/patologia , Hemoglobinas/metabolismo , Humanos , Hipopotassemia/etiologia , Hipopotassemia/patologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Meningite Criptocócica/microbiologia , Meningite Criptocócica/mortalidade , Meningite Criptocócica/patologia , Neutropenia/prevenção & controle , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes. METHODS: Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality. RESULTS: Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0-1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4-11.1), high peripheral white blood cell count (>10 × 10(9) cells/L; OR, 8.7; 95% CI, 2.5-30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART). CONCLUSIONS: CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes.
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Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções por HIV/complicações , Meningite Criptocócica/mortalidade , Adulto , África , Líquido Cefalorraquidiano/microbiologia , Estudos de Coortes , Contagem de Colônia Microbiana , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Estudos Longitudinais , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/etiologia , Estudos Prospectivos , Fatores de Risco , TailândiaRESUMO
Oral drug absorption kinetics are usually established in populations with a properly functioning gastrointestinal tract. However, many diseases and therapeutics can alter gastrointestinal physiology and cause diarrhea. The extent of diarrhea-associated impact on drug pharmacokinetics has not been quantitatively described. To address this knowledge gap, we used a population pharmacokinetic modeling approach with data collected in a phase IIa study of matched human immunodeficiency virus (HIV)-infected adults with/without cryptosporidiosis and diarrhea to examine diarrhea-associated impact on oral clofazimine pharmacokinetics. A population pharmacokinetic model was developed with 428 plasma samples from 23 HIV-infected adults with/without Cryptosporidium infection using nonlinear mixed-effects modeling. Covariates describing cryptosporidiosis-associated diarrhea severity (e.g., number of diarrhea episodes, diarrhea grade) or HIV infection (e.g., viral load, CD4+ T cell count) were evaluated. A two-compartment model with lag time and first-order absorption and elimination best fit the data. Maximum diarrhea grade over the study duration was found to be associated with a more than sixfold reduction in clofazimine bioavailability. Apparent clofazimine clearance, intercompartmental clearance, central volume of distribution, and peripheral volume of distribution were 3.71 L/h, 18.2 L/h (interindividual variability [IIV] 45.0%), 473 L (IIV 3.46%), and 3434 L, respectively. The absorption rate constant was 0.625 h-1 (IIV 149%) and absorption lag time was 1.83 h. In conclusion, the maximum diarrhea grade observed for the duration of oral clofazimine administration was associated with a significant reduction in clofazimine bioavailability. Our results highlight the importance of studying disease impacts on oral therapeutic pharmacokinetics to inform dose optimization and maximize the chance of treatment success.
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Criptosporidiose , Cryptosporidium , Infecções por HIV , Adulto , Humanos , Clofazimina/farmacocinética , Clofazimina/uso terapêutico , Diarreia/tratamento farmacológico , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos Fase II como AssuntoRESUMO
Background: Hospital admission due to breathlessness carries a significant burden to patients and healthcare systems, particularly impacting people in low-income countries. Prompt appropriate treatment is vital to improve outcomes, but this relies on accurate diagnostic tests which are of limited availability in resource-constrained settings. We will provide an accurate description of acute breathlessness presentations in a multicentre prospective cohort study in Malawi, a low resource setting in Southern Africa, and explore approaches to strengthen diagnostic capacity. Objectives: Primary objective: Delineate between causes of breathlessness among adults admitted to hospital in Malawi and report disease prevalence. Secondary objectives : Determine patient outcomes, including mortality and hospital readmission 90 days after admission; determine the diagnostic accuracy of biomarkers to differentiate between heart failure and respiratory infections (such as pneumonia) including brain natriuretic peptides, procalcitonin and C-reactive protein. Methods: This is a prospective longitudinal cohort study of adults (≥18 years) admitted to hospital with breathlessness across two hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Chiradzulu, Malawi. Patients will be consecutively recruited within 24 hours of emergency presentation and followed-up until 90 days from hospital admission. We will conduct enhanced diagnostic tests with robust quality assurance and quality control to determine estimates of disease pathology. Diagnostic case definitions were selected following a systematic literature search. Discussion: This study will provide detailed epidemiological description of adult hospital admissions due to breathlessness in low-income settings, which is currently poorly understood. We will delineate between causes using established case definitions and conduct nested diagnostic evaluation. The results have the potential to facilitate development of interventions targeted to strengthen diagnostic capacity, enable prompt and appropriate treatment, and ultimately improve both patient care and outcomes.
BACKGROUND: People admitted to hospital with symptoms of breathlessness are often severely ill and need quick, accurate assessment to facilitate timely initiation of appropriate treatments. In low resource settings, such as Malawi, limited access to diagnostic equipment impedes patient assessment. Failure to identify and treat the underlying diagnosis may lead to preventable death. AIMS: This cohort study aims to delineate between common, treatable causes of breathlessness among adult patients admitted to hospital in Malawi and measure survival. We will also evaluate the performance of blood markers to diagnose and differentiate between conditions. The results will help us develop context-appropriate diagnostic and treatment algorithms based on resources available in the health system Methods in brief: We will recruit adult patients who present to hospital with breathlessness in a central national referral hospital (Queen Elizabeth Central Hospital, Blantyre), and a district hospital (Chiradzulu District Hospital, Chiradzulu). We will conduct enhanced diagnostic tests to determine causes of breathlessness against internationally accepted diagnostic guidelines. Patients will be followed up throughout their hospital admission and after discharge, until 90 days. INTERPRETATION: This study aligns with World Health Assembly resolutions on 'Strengthening diagnostics capacity' and on 'Integrated emergency, critical and operative care for universal health coverage and protection from health emergencies'. The results of this study will have the potential to facilitate development of interventions targeted to strengthen diagnostic capacity, enable prompt and appropriate treatment, and ultimately improve care and outcomes for acutely unwell patients.
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BACKGROUND: Cryptosporidium is a gastrointestinal pathogen that presents a serious opportunistic infection in immunocompromised individuals including those living with human immunodeficiency syndrome. The CRYPTOFAZ trial, previously published, was conducted in Malawi to evaluate the efficacy of clofazimine in response to an unmet need for drugs to treat cryptosporidiosis in HIV populations. A combination of rapid diagnostic tests, ELISA, qPCR, and conventional sequencing were employed to detect Cryptosporidium in 586 individuals during pre-screening and monitor oocyst shedding and identify enteric co-pathogens in 22 enrolled/randomized participants during the in-patient period and follow-up visits. METHODOLOGY: Oocyst shedding as measured by qPCR was used to determine primary trial outcomes, however pathogen was detected even at trial days 41-55 in individuals randomized to either clofazimine or placebo arms of the study. Therefore, in this work we re-examine the trial outcomes and conclusions in light of data from the other diagnostics, particularly ELISA. ELISA data was normalized between experiments prior to comparison to qPCR. The amount of all identified enteric pathogens was examined to determine if co-pathogens other than Cryptosporidium were major causative agents to a participant's diarrhea. CONCLUSION: ELISA had higher sample-to-sample variability and proved to be equally or less sensitive than qPCR in detecting Cryptosporidium positive samples. Compared to qPCR, ELISA had equal or greater specificity in detecting Cryptosporidium negative samples. Sequencing identified several Cryptosporidium species including viatorum which has never been identified in Malawi and Southern Africa. In addition to Cryptosporidium, enterotoxigenic E. coli was also identified as a pathogen in diarrheagenic amounts in 4 out of 22 participants.
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Criptosporidiose , Cryptosporidium , Escherichia coli Enterotoxigênica , Humanos , Animais , Criptosporidiose/diagnóstico , Criptosporidiose/tratamento farmacológico , Cryptosporidium/genética , Clofazimina , Reação em Cadeia da Polimerase , Ensaio de Imunoadsorção Enzimática , OocistosRESUMO
BACKGROUND: Cryptococcal meningitis is a major cause of human immunodeficiency virus (HIV)-associated morbidity and mortality in Africa. Improved oral treatment regimens are needed because amphotericin B is neither available nor feasible in many centers. Fluconazole at a dosage of 1200 mg per day is more fungicidal than at a dosage of 800 mg per day, but mortality rates remain unacceptably high. Therefore, we examined the effect of adding oral flucytosine to fluconazole. METHODS: From 13 February through 2 December 2008, HIV-seropositive, antiretroviral-naive patients experiencing their first episode of cryptococcal meningitis were randomized to receive (1) 14 days of fluconazole (1200 mg per day) alone or (2) in combination with flucytosine (100 mg/kg per day) followed by fluconazole (800 mg per day), with both groups undergoing 10 weeks of follow-up. The primary end point was early fungicidal activity, derived from quantitative cerebrospinal fluid cultures on days 1, 3, 7, and 14. Secondary end points were safety and 2- and 10-week mortality. RESULTS: Forty-one patients were analyzed. Baseline mental status, cryptococcal burden, opening pressure, CD4(+) cell count, and HIV load were similar between groups. Combination therapy was more fungicidal than fluconazole alone (mean early fungicidal activity +/- standard deviation -0.28 +/- 0.17 log colony-forming units [CFU]/mL per day vs -0.11 +/- 0.09 log CFU/mL per day; P < .001). The combination arm had fewer deaths by 2 weeks (10% vs 37%) and 10 weeks (43% vs 58%). More patients had grade III or IV neutropenia with combination therapy (5 vs 1, within the first 2 weeks; P = .20), but there was no increase in infection-related adverse events. CONCLUSIONS: The results suggest that optimal oral treatment for cryptococcal meningitis is high-dose fluconazole with flucytosine. Efforts are needed to increase availability of flucytosine in Africa. Clinical trials registration. isrctn.org Identifier: ISRCTN02725351.
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Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico , Flucitosina/uso terapêutico , Meningite Criptocócica/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Administração Oral , Adulto , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Líquido Cefalorraquidiano/microbiologia , Cryptococcus/isolamento & purificação , Quimioterapia Combinada , Feminino , Fluconazol/administração & dosagem , Fluconazol/efeitos adversos , Flucitosina/administração & dosagem , Flucitosina/efeitos adversos , Infecções por HIV/complicações , Humanos , Malaui , Masculino , Meningite Criptocócica/microbiologia , Meningite Criptocócica/mortalidade , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: An effective drug to treat cryptosporidial diarrhea in HIV-infected individuals is a global health priority. Promising drugs need to be evaluated in endemic areas which may be challenged by both lack of resources and experience to conduct International Committee of Harmonisation-Good Clinical Practice (ICH-GCP)-compliant clinical trials. METHODS: We present the challenges and lessons learned in implementing a phase 2A, randomized, double-blind, placebo-controlled trial of clofazimine, in treatment of cryptosporidiosis among HIV-infected adults at a single site in Malawi. RESULTS: Primary challenges are grouped under study initiation, study population, study implementation, and cultural issues. The lessons learned primarily deal with regulatory system and operational barriers, and recommendations can be applied to other human experimental trials in low- and middle-income countries, specifically in sub-Saharan Africa. CONCLUSION: This study demonstrated that initiating and implementing human experimental trials in sub-Saharan Africa can be challenging. However, solutions exist and successful execution requires careful planning, ongoing evaluation, responsiveness to new developments, and oversight of all trial operations.
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Criptosporidiose/tratamento farmacológico , Diarreia/tratamento farmacológico , Infecções por HIV , Projetos de Pesquisa , Adulto , Animais , Ensaios Clínicos Fase II como Assunto , Cryptosporidium , Diarreia/parasitologia , Infecções por HIV/congênito , Humanos , Malaui , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Perinatal depression is a common condition of pregnancy and the postpartum period. Depression negatively affects engagement in HIV care, but systematic screening for perinatal depression is not done in most sub-Saharan African countries. Estimating the burden and timing of perinatal depression can help inform medical programs with the current scale-up of HIV care for pregnant women. METHODS: Women (nâ¯=â¯299) initiating antiretroviral therapy for HIV were recruited from a government antenatal clinic in Malawi in 2015-2016 into a cohort study. Probable perinatal depression was assessed at enrollment and at 6 weeks and 3, 6, and 12 months postpartum with the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire-9 (PHQ-9). We estimated point prevalence and incidence of depression as well as concordance between EPDS and PHQ-9 scores. RESULTS: One in ten women screened positive for probable antenatal depression, whereas 1-6% screened positive postpartum. Sensitivity analyses to account for loss to follow-up suggested that postpartum depression prevalence could have ranged from 1-11%. At postpartum time points, 0-3% of participants screened positive for incident probable depression. EPDS and PHQ-9 scores were concordant for 96% of assessments during antenatal and postpartum visits. LIMITATIONS: Lack of diagnostic psychiatric evaluation precludes actual diagnosis of major depression, and social desirability bias may have contributed to low postpartum scores. CONCLUSIONS: Probable depression was more common during the antenatal period than postpartum among our participants. Given the association between depression and negative HIV outcomes, screening for depression during pregnancy should be integrated into antenatal HIV care.
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Antirretrovirais/uso terapêutico , Depressão Pós-Parto/epidemiologia , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Estudos de Coortes , Depressão Pós-Parto/psicologia , Transtorno Depressivo Maior/diagnóstico , Feminino , Infecções por HIV/psicologia , Humanos , Incidência , Malaui/epidemiologia , Comportamento Materno , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/psicologia , Cuidado Pré-Natal/estatística & dados numéricos , Prevalência , Probabilidade , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
BACKGROUND: Effective antiretroviral therapy during pregnancy minimizes the risk of vertical HIV transmission. Some women present late in their pregnancy for first antenatal visit; whether these women achieve viral suppression by delivery and how suppression varies with time on ART is unclear. METHODS: We conducted a prospective cohort study of HIV-infected pregnant women initiating antiretroviral therapy for the first time at Bwaila Hospital in Lilongwe, Malawi from June 2015 to November 2016. Multivariable Poisson models with robust variance estimators were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of the association between duration of ART and both viral load (VL) ≥1000 copies/ml and VL ≥40 copies/ml at delivery. RESULTS: Of the 252 women who had viral load testing at delivery, 40 (16%) and 78 (31%) had VL ≥1000 copies/ml and VL ≥40 copies/ml, respectively. The proportion of women with poor adherence to ART was higher among women who were on ART for ≤12 weeks (9/50 = 18.0%) than among those who were on ART for 13-35 weeks (18/194 = 9.3%). Compared to women who were on ART for ≤12 weeks, women who were on ART for 13-20 weeks (RR = 0.52; 95% CI: 0.36-0.74) or 21-35 weeks (RR = 0.26; 95% CI: 0.14-0.48) had a lower risk of VL ≥40 copies/ml at delivery. Similar comparisons for VL ≥1000 copies/ml at delivery showed decrease in risk although not significant for those on ART 13-20 weeks. CONCLUSION: Longer duration of ART during pregnancy was associated with suppressed viral load at delivery. Early ANC attendance in pregnancy to facilitate prompt ART initiation for HIV-positive women is essential in the effort to eliminate HIV vertical transmission.
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Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Gravidez , Resultado da Gravidez , Resultado do Tratamento , Carga ViralRESUMO
: We assessed the effect of fluconazole 1200âmg/day on the QT interval in cryptococcal meningitis patients. Mean corrected QT (QTc) change from baseline to day 7 was 10.1âms (IQR: -28 to 46âms) in the fluconazole treatment group and -12.6âms (IQR: -39 to 13.5âms) in those not taking fluconazole (Pâ=â0.04). No significant increase in QTc measurements over 500âms was observed with fluconazole. Nevertheless, it remains important to correct any electrolyte imbalance and avoid concomitant drugs that may increase QTc.
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Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Fluconazol/administração & dosagem , Fluconazol/efeitos adversos , Infecções por HIV/complicações , Sistema de Condução Cardíaco/efeitos dos fármacos , Meningite Criptocócica/tratamento farmacológico , Adulto , África , HumanosRESUMO
BACKGROUND: Cryptococcal meningitis in Africa is associated with up to 70% mortality at 3 months and 500â000 deaths annually. We examined strategies to improve on fluconazole (FLU) monotherapy: addition of flucytosine (5-FC) and/or addition of short-course amphotericin B (AmB). METHODS: In step 1, previously reported, patients were randomized to receive FLU 1200âmg per day with or without 5-FC 100âmg/kg per day for 14 days. In step 2, 43 patients were similarly randomized, with addition of AmB 1âmg/kg per day for 7 days to both arms. After 2 weeks, patients received FLU monotherapy and were followed to 10 weeks. The primary endpoint was rate of clearance of infection (early fungicidal activity, EFA). Secondary endpoints related to safety and mortality. RESULTS: Forty patients (25% with Glasgow Coma Scale <15) were analyzed. EFA for the triple combination arm was greater than that for AmB-FLU: -0.50â±â0.15 log CFU/day vs. -0.38â±â0.19 log colony forming units per day (P=0.03); and greater than that for step 1 with FLU-5-FC (-0.28â±â0.17) or FLU alone (-0.11â±â0.09). Combined analysis across steps revealed that addition of 5-FC and AmB had significant, independent additive effects on EFA, with trends toward fewer early deaths with addition of 5-FC (4/41 vs. 11/39, Pâ=â0.05) and fewer deaths overall with addition of AmB (13/39 vs. 20/40, Pâ=â0.1). CONCLUSION: Addition of 5-FC and short-course AmB to high-dose FLU significantly enhanced EFA and may be associated with favorable trends in survival. Both these strategies should be tested in a larger phase III study.