RESUMEN
BACKGROUND: Syphilis infection during pregnancy leads to avoidable morbidity and mortality and remains a significant problem in sub-Saharan Africa. Despite global initiatives to increase the proportion of pregnant women screened, implementation has been slow. We sought to investigate the feasibility of adding syphilis screening within an integrated antenatal HIV clinic. METHODS: Pregnant women attending the HIV antenatal clinic were sequentially enrolled and consenting participants answered a questionnaire on sexual behavior and previous pregnancies, provided sociodemographic data, and were tested using rapid plasmin reagin (RPR). If positive, participants were treated with benzathine penicillin. All were given a partner notification slip and were followed up after delivery to determine birth outcomes. RESULTS: 584 of 606 (95.7%) women approached and consented to test for syphilis. 570 women were enrolled (median age 29 (IQR 25-32) with a median (IQR) CD4 of 372 (257-569) cells/µL). Of the 5.1% (29/570) with a positive RPR, all were asymptomatic, were successfully contacted, and treated with benzathine penicillin without adverse reactions. Overall, 61 (12.1%) of the participants had an adverse birth outcome. In the bivariate analysis, only age was significantly different between those with and without a positive RPR (RR = 1.15, 95% CI 1.065-1.248; p < 0.001). Partners of only 10 (34.5%) participants returned for treatment. CONCLUSIONS: Structural interventions such as opt-out testing for syphilis within integrated HIV-antenatal care clinics are feasible and capitalize on the excellent care programs that have already been established for HIV care. Novel approaches are required for partner notification.
Asunto(s)
Infecciones por VIH , Complicaciones Infecciosas del Embarazo/epidemiología , Sífilis/epidemiología , Adulto , África del Sur del Sahara/epidemiología , Instituciones de Atención Ambulatoria , Trazado de Contacto , Estudios de Factibilidad , Femenino , Humanos , Penicilina G Benzatina/uso terapéutico , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Diagnóstico Prenatal , Parejas Sexuales , Encuestas y Cuestionarios , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico , Servicios Urbanos de Salud , Adulto JovenRESUMEN
BACKGROUND: Treatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir. METHODS: A two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adults stable on 400/100 mg of lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (ClinicalTrials.gov, NCT 00619944). Each participant received a single dose of 80/480 mg of artemether/lumefantrine under continuous cardiac function monitoring. Plasma concentrations of artemether, dihydroartemisinin and lumefantrine were measured. RESULTS: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly reduced artemether maximum concentration (C(max)) and area under the concentration-time curve (AUC) [median (range): 112 (20-362) versus 56 (17-236) ng/mL, P = 0.03; and 264 (92-1129) versus 151 (38-606) ng · h/mL, P < 0.01]. Dihydroartemisinin C(max) and AUC were not affected [66 (10-111) versus 73 (31-224) ng/mL, P = 0.55; and 213 (68-343) versus 175 (118-262) ng · h/mL P = 0.27]. Lumefantrine C(max) and AUC increased during co-administration [2532 (1071-5957) versus 7097 (2396-9462) ng/mL, P < 0.01; and 41,119 (12,850-125,200) versus 199,678 (71,205-251,015) ng · h/mL, P < 0.01]. CONCLUSIONS: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly increases lumefantrine exposure, but decreases artemether exposure. Population pharmacokinetic and pharmacodynamic trials will be highly valuable in evaluating the clinical significance of this interaction and determining whether dosage modifications are indicated.
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Antimaláricos/farmacocinética , Terapia Antirretroviral Altamente Activa/métodos , Interacciones Farmacológicas , Infecciones por VIH/tratamiento farmacológico , Malaria/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/administración & dosificación , Antimaláricos/administración & dosificación , Femenino , Infecciones por VIH/complicaciones , Humanos , Malaria/complicaciones , Masculino , UgandaRESUMEN
OBJECTIVES: Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug-drug interactions between artemether/lumefantrine and efavirenz or nevirapine. METHODS: We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state. Artemether, dihydroartemisinin, lumefantrine, efavirenz and nevirapine plasma concentrations were measured and compared. RESULTS: Efavirenz significantly reduced artemether maximum concentration (C(max)) and plasma AUC (median 29 versus 12 ng/mL, Pâ<â0.01, and 119 versus 25 ngâ·âh/mL, Pâ<â0.01), dihydroartemisinin C(max) and AUC (median 120 versus 26 ng/mL, Pâ<â0.01, and 341 versus 84 ngâ·âh/mL, Pâ<â0.01), and lumefantrine C(max) and AUC (median 8737 versus 6331 ng/mL, Pâ=â0.03, and 280â370 versus 124â381 ngâ·âh/mL, Pâ<â0.01). Nevirapine significantly reduced artemether C(max) and AUC (median 28 versus 11 ng/mL, Pâ<â0.01, and 123 versus 34 ngâ·âh/mL, Pâ<â0.01) and dihydroartemisinin C(max) and AUC (median 107 versus 59 ng/mL, Pâ<â0.01, and 364 versus 228 ngâ·âh/mL, Pâ<â0.01). Lumefantrine C(max) and AUC were non-significantly reduced by nevirapine. Artemether/lumefantrine reduced nevirapine C(max) and AUC (median 8620 versus 4958 ng/mL, Pâ<â0.01, and 66â329 versus 35â728 ngâ·âh/mL, Pâ<â0.01), but did not affect efavirenz exposure. CONCLUSIONS: Co-administration of artemether/lumefantrine with efavirenz or nevirapine resulted in a reduction in artemether, dihydroartemisinin, lumefantrine and nevirapine exposure. These drug interactions may increase the risk of malaria treatment failure and development of resistance to artemether/lumefantrine and nevirapine. Clinical data from population pharmacokinetic and pharmacodynamic trials evaluating the impact of these drug interactions are urgently needed.
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Antimaláricos/farmacocinética , Artemisininas/farmacocinética , Benzoxazinas/farmacocinética , Interacciones Farmacológicas , Etanolaminas/farmacocinética , Fluorenos/farmacocinética , Nevirapina/farmacocinética , Adulto , Alquinos , Fármacos Anti-VIH/administración & dosificación , Antimaláricos/administración & dosificación , Combinación Arteméter y Lumefantrina , Artemisininas/administración & dosificación , Benzoxazinas/administración & dosificación , Estudios Cruzados , Ciclopropanos , Combinación de Medicamentos , Etanolaminas/administración & dosificación , Femenino , Fluorenos/administración & dosificación , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Malaria/complicaciones , Malaria/tratamiento farmacológico , Masculino , Nevirapina/administración & dosificación , Plasma/química , UgandaRESUMEN
BACKGROUND: Severe malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria. METHODS: Fourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134). RESULTS: All study participants achieved prompt resolution of symptoms and complete parasite clearance with median (range) parasite clearance time of 17 (8-24) hours. Median (range) maximal artesunate concentration (Cmax) was 3260 (1020-164000) ng/mL, terminal elimination half-life (T1/2) was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290-111256) ng·h/mL. Median (range) dihydroartemisinin Cmax was 3140 (1670-9530) ng/mL, with Tmax of 0.14 (0.6 - 6.07) hours and T1/2 of 1.31 (0.8-2.8) hours. Dihydroartemisinin AUC was 3492 (2183-6338) ng·h/mL. None of the participants reported adverse events. CONCLUSIONS: Plasma concentrations of artesunate and dihydroartemisinin were achieved rapidly with rapid and complete symptom resolution and parasite clearance with no adverse events.
Asunto(s)
Antimaláricos/farmacología , Antimaláricos/farmacocinética , Artemisininas/farmacología , Artemisininas/farmacocinética , Malaria/tratamiento farmacológico , Adulto , Antimaláricos/administración & dosificación , Antimaláricos/sangre , Artemisininas/administración & dosificación , Artemisininas/sangre , Artesunato , Cromatografía Liquida , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Plasma/química , Espectrometría de Masas en Tándem , UgandaRESUMEN
In many resource-poor countries, CD4 count thresholds of eligibility for antiretroviral treatment (ART) were initially low (<200 cells/mm(3)) but are now being increased to improve patient survival and to reduce HIV transmission. There are few quantitative data on the effect of such increases on the demand for ART. The objective of this study was to measure HIV prevalence and the proportion of HIV-positives eligible for antiretroviral therapy at different CD4 cut-off levels among users of public health care services in Kampala, Uganda. We recruited 1200 adults from three primary care clinics in Kampala, including equal numbers of family planning (FP) clients, pregnant women, adult patients with any complaint, and persons seeking HIV counseling and testing. All participants were screened for HIV and those positive had a CD4 count done. HIV prevalence in all patients was 16.9% (203/1200). ART eligibility based on CD4 counts significantly increased from 36% at a 200 cells/mm(3) cut-off to 44% at 250 cells and to 57% at 350 cells cut-off (p for χ(2) trend<0.001). We concluded that changing cut-off levels to higher CD4 counts will significantly increase patient load in Kampala's primary care clinics, but a phased implementation should minimize negative effects on quality of care.
Asunto(s)
Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Adolescente , Adulto , Distribución por Edad , Recuento de Linfocito CD4 , Determinación de la Elegibilidad , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Humanos , Masculino , Evaluación de Necesidades , Prevalencia , Atención Primaria de Salud/estadística & datos numéricos , Uganda/epidemiología , Adulto JovenRESUMEN
Early mortality after initiation of antiretroviral therapy (ART) occurs in 9-39% of patients in sub-Saharan Africa. A significant proportion of deaths are attributable to tuberculosis (TB). Low baseline CD4 T-cell count and low body mass index (BMI) are strongly associated with early mortality. We hypothesized that initiation of ART concurrent with presumptive anti-TB chemotherapy in high-risk patients would reduce mortality within the first 6 months by treating unrecognized TB. From October 2011 to December 2012, ART-naive, smear-negative participants with a CD4 T-cell count < 50 cells/µL and BMI < 18 kg/m2 were randomly assigned to undergo either empiric four-drug anti-TB treatment followed 2 weeks later by efavirenz-based ART (N = 23) (ART + TB) or ART only (N = 20). This open-label, 1:1 randomized, controlled trial took place in Uganda, Mozambique, and Gabon and was stopped prematurely by the sponsor for slow recruitment. Overall, the 43 participants had a median CD4 of 22 (interquartile range [IQR]: 9-35) cells/µL and a median BMI of 17.5 (IQR: 16.6-18.0) kg/m2 The mortality was 14% (95% confidence interval [CI]: 5.3-27.9); two (10.0%) participants (ART-only group), and four (17.4%; ART + TB group). The associated hazard ratio (HR) for all-cause mortality was 1.6 (95% CI: 0.30-8.90). Despite limited enrollment, the study did not suggest that empiric TB treatment in severely immunosuppressed patients with low BMI decreased mortality and, had an HR in the opposite direction than expected. Notably, two participants in the ART + TB group died with autopsy-confirmed drug-induced hepatotoxicity. Improved TB diagnostics sensitive in immunosuppressed patients presenting late to care are urgently needed for more targeted interventions.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Antituberculosos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Adulto , África del Sur del Sahara/epidemiología , Fármacos Anti-VIH/administración & dosificación , Índice de Masa Corporal , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/epidemiología , Humanos , MasculinoRESUMEN
BACKGROUND: The objective of the present study was to assess whether the high-density lipoprotein cholesterol (HDL-c)-increasing effect of nevirapine (NVP), as observed in human immunodeficiency virus type 1 (HIV-1)-infected subjects, at least in part may relate to intrinsic properties of NVP. METHODS: At 2, 6, and 12 weeks after birth, complete lipid profiles as well as plasma apolipoproteins levels were assessed in 80 HIV-uninfected newborns, half of whom received NVP and half lamivudine (3TC), respectively. Newborns were randomly selected from a randomized trial in which NVP or 3TC had been administered to HIV-uninfected infants born to HIV-infected mothers to try and prevent HIV-1 transmission from occurring during breast-feeding. RESULTS: After 6 weeks of therapy, the expected physiological decline in HDL-c levels in the newborns was attenuated in infants treated with NVP, compared with levels in those treated with 3TC. Apolipoprotein A-I (apoA-I) levels were higher at all time points in the NVP arm than they were in the 3TC arm (P=.02), reaching peak levels at 6 weeks. The difference in HDL-c was no longer significant at 12 weeks. CONCLUSIONS: apoA-I levels and HDL-c were elevated in HIV-1-uninfected newborns receiving NVP, compared with those receiving 3TC. These data support that NVP may indeed have intrinsic apoA-I and HDL-c elevating properties in humans.