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2.
Nurse Pract ; 47(4): 10-18, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35349512

RESUMO

ABSTRACT: Sexually transmitted infections (STIs) are common and costly, with about 26 million STIs occurring each year in the US. Guidelines for the prevention and management of STIs are updated periodically. In 2021, the CDC updated its guidelines for the treatment of STIs. This article provides information on the most recent updates on managing STIs to help advanced practice nurses in their practice.


Assuntos
Prática Avançada de Enfermagem , Infecções por HIV , Infecções Sexualmente Transmissíveis , Infecções por HIV/prevenção & controle , Humanos , Infecções Sexualmente Transmissíveis/prevenção & controle
3.
BMC Evol Biol ; 11: 62, 2011 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-21385447

RESUMO

BACKGROUND: Replicate experiments are often difficult to find in evolutionary biology, as this field is inherently an historical science. However, viruses, bacteria and phages provide opportunities to study evolution in both natural and experimental contexts, due to their accelerated rates of evolution and short generation times. Here we investigate HIV-1 evolution by using a natural model represented by monozygotic twins infected synchronically at birth with an HIV-1 population from a shared blood transfusion source. We explore the evolutionary processes and population dynamics that shape viral diversity of HIV in these monozygotic twins. RESULTS: Despite the identical host genetic backdrop of monozygotic twins and the identical source and timing of the HIV-1 inoculation, the resulting HIV populations differed in genetic diversity, growth rate, recombination rate, and selection pressure between the two infected twins. CONCLUSIONS: Our study shows that the outcome of evolution is strikingly different between these two "replicates" of viral evolution. Given the identical starting points at infection, our results support the impact of random epigenetic selection in early infection dynamics. Our data also emphasize the need for a better understanding of the impact of host-virus interactions in viral evolution.


Assuntos
Doenças em Gêmeos/virologia , Infecções por HIV/virologia , HIV-1/genética , Gêmeos Monozigóticos , Evolução Molecular , Variação Genética , Humanos , Masculino , Filogenia , Dinâmica Populacional , RNA Viral/genética , Análise de Sequência de RNA
4.
Public Health Rep ; 136(2): 148-153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33541219

RESUMO

Force health protection (FHP) is defined as "the prevention of disease and injury in order to protect the strength and capabilities" of any service population. FHP was the foundational principal of the US Public Health Service (USPHS). President John Adams' signing of An Act for Sick and Disabled Seamen on July 16, 1798, marked the first dedication of US federal resources to ensuring the well-being of US civilian sailors and Naval service members. On January 4, 1889, President Cleveland enacted the USPHS Commissioned Corps, creating the world's first (and still only) uniformed service dedicated to promoting, protecting, and advancing the health and safety of the United States and the world. Building on the lessons of the 2014-2015 response to the Ebola virus pandemic, the Corps Care program was formalized in 2017 to establish and implement a uniform and comprehensive strategy to meet the behavioral health, medical, and spiritual needs of all Commissioned Corps officers. Its role was expanded in response to the coronavirus disease 2019 (COVID-19) pandemic, which has placed unprecedented demands on health care workers and spotlighted the need for FHP strategies. We describe the FHP roles of the Corps Care program for the resiliency of Commission Corps officers in general and the Corps' impact during the response to the COVID-19 pandemic. Qualitative analysis of FHP discussions with deployed officers highlights the unique challenges to FHP presented by the pandemic response.


Assuntos
COVID-19/epidemiologia , Pessoal de Saúde/psicologia , Doença pelo Vírus Ebola/epidemiologia , Resiliência Psicológica , United States Public Health Service , COVID-19/terapia , Doença pelo Vírus Ebola/terapia , Estados Unidos
5.
Sci Rep ; 10(1): 327, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941887

RESUMO

In recent years Bamako has been faced with an emerging threat from multidrug resistant TB (MDR-TB). Whole genome sequence analysis was performed on a subset of 76 isolates from a total of 208 isolates recovered from tuberculosis patients in Bamako, Mali between 2006 and 2012. Among the 76 patients, 61(80.3%) new cases and 15(19.7%) retreatment cases, 12 (16%) were infected by MDR-TB. The dominant lineage was the Euro-American lineage, Lineage 4. Within Lineage 4, the Cameroon genotype was the most prevalent genotype (n = 20, 26%), followed by the Ghana genotype (n = 16, 21%). A sub-clade of the Cameroon genotype, which emerged ~22 years ago was likely to be involved in community transmission. A sub-clade of the Ghana genotype that arose approximately 30 years ago was an important cause of MDR-TB in Bamako. The Ghana genotype isolates appeared more likely to be MDR than other genotypes after controlling for treatment history. We identified a clade of four related Beijing isolates that included one MDR-TB isolate. It is a major concern to find the Cameroon and Ghana genotypes involved in community transmission and MDR-TB respectively. The presence of the Beijing genotype in Bamako remains worrying, given its high transmissibility and virulence.


Assuntos
Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adolescente , Adulto , Camarões , Criança , Pré-Escolar , Feminino , Genótipo , Gana , Humanos , Lactente , Recém-Nascido , Masculino , Mali , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Fatores de Risco , Tuberculose/diagnóstico , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto Jovem
6.
Artigo em Inglês | MEDLINE | ID: mdl-34355138

RESUMO

Diagnosis of HIV infections in resource-limited countries like Mali is based on Rapid Diagnostic Tests (RDTs). The RDTs are diagnostic assays designed for use at the Point-Of-Care (POC), which is quick, cost-effective and easy to perform. However, in these countries, the tests are commonly used without any initial evaluation or monitoring of their performance despite high levels of HIV strain diversity and rapid evolution of the virus. In this study, the reliability and accuracy of HIV RDTs (Determine™, Multispot™, SD Bioline™) used in Mali, where HIV-1 and HIV-2 co-exist, were evaluated from August 2004 to November 2017. A total of 1303 samples from new HIV-suspect patients in Bamako were tested for HIV-1 and HIV-2 using the RDT Determine™, followed by ELISA and Western Blot (WB). The Determine™ test showed a robust diagnostic sensitivity of 98.7% [CI 95: 97.59-99.37] and a diagnostic specificity of 99.2% [CI 95: 98.22-99.67]. The Multispot™ assay showed a diagnostic sensitivity of 98.77% [CI 95: 97.59-99.37] and a diagnostic specificity of 99.2% [CI 95: 98.22-99.67]. The diagnostic sensitivity and specificity of SD Bioline™ HIV-1/2 were 100% [CI 95:72.25-100] and 88.89% [CI 95: 56.50- 98.71], respectively. These data indicate excellent performance for HIV RDTs in Mali and we recommend the use of Determine™ HIV-1/2 for HIV screening and Multispot™ for discriminating HIV-2 from HIV-1 infections.

7.
Int J Infect Dis ; 81: 149-155, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30772470

RESUMO

BACKGROUND: MDR-TB is a major threat to global TB control. In 2015, 580,000 were treated for MDR-TB worldwide. The worldwide roll-out of GeneXpert MTB/RIF® has improved diagnosis of MDR-TB; however, in many countries laboratories are unable to assess drug resistance and clinical predictors of MDR-TB could help target suspected patients. In this study, we aimed to determine the clinical factors associated with MDR-TB in Bamako, Mali. METHODS: We performed a cross-sectional study of 214 patients with presumed MDR-TB admitted to University of Bamako Teaching Hospital, Point-G between 2007 and 2016. We calculated crude and adjusted odds ratios for MDR-TB disease diagnosis using SPSS. RESULTS: We found that age ≤40years (OR=2.56. 95% CI: 1.44-4.55), two courses of prior TB treatment (OR=3.25, 95% CI: 1.44-7.30), TB treatment failure (OR=3.82, 95% CI 1.82-7.79), sputum microscopy with 3+ bacilli load (OR=1.98, 95% CI: 1.13-3.48) and a history of contact with a TB patient (OR=2.48, 95% CI: 1.11-5.50) were significantly associated with confirmation of MDR-TB disease. HIV was not a risk factor for MDR-TB (aOR=0.88, 95% CI: 0.34-1.94). CONCLUSION: We identified several risk factors that could be used to identify MDR-TB suspects and prioritize them for laboratory confirmation. Prospective studies are needed to understand factors associated with TB incidence and clinical outcomes of TB treatment and disease.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
8.
Nurse Pract ; 43(8): 28-34, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29985197

RESUMO

Guidelines for the prevention and management of sexually transmitted infections (STIs) are updated periodically while new science is continuously developed. Advanced practice registered nurses implement clinical decisions based on current guidelines and evidence. This article provides recent updates on managing STIs.


Assuntos
Prática Avançada de Enfermagem , Guias de Prática Clínica como Assunto , Infecções Sexualmente Transmissíveis/enfermagem , Humanos
9.
PLoS One ; 13(12): e0208603, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30540823

RESUMO

OBJECTIVE: Ancestral M. tuberculosis complex lineages such as M. africanum are underrepresented among retreatment patients and those with drug resistance. To test the hypothesis that they respond faster to TB treatment, we determined the rate of smear conversion of new pulmonary tuberculosis patients in Bamako, Mali by the main MTBc lineages. METHODS: Between 2015 and 2017, we conducted a prospective cohort study of new smear positive pulmonary tuberculosis patients in Bamako. Confirmed MTBc isolates underwent genotyping by spoligotyping for lineage classification. Patients were followed at 1 month (M), 2M and 5M to measure smear conversion in auramine (AR) and Fluorescein DiAcetate (FDA) vital stain microscopy. RESULT: All the first six human MTBc lineages were represented in the population, plus M. bovis in 0.8% of the patients. The most widely represented lineage was the modern Euro-American lineage (L) 4, 57%, predominantly the T family, followed by L6 (M. africanum type 2) in 22.9%. Ancestral lineages 1, 5, 6 and M. bovis combined amounted to 28.8%. Excluding 25 patients with rifampicin resistance, smear conversion, both by AR and FDA, occurred later in L6 compared to L4 (HR 0.80 (95% CI 0.66-0.97) for AR, and HR 0.81 (95%CI 0.68-0.97) for FDA). In addition we found that HIV negative status, higher BMI at day 0, and patients with smear grade at baseline ≤ 1+ were associated with earlier smear conversion. CONCLUSION: The six major human lineages of the MTBc all circulate in Bamako. Counter to our hypothesis, we found that patients diseased with modern M. tuberculosis complex L4 respond faster to TB treatment than those with M. africanum L6.


Assuntos
Técnicas de Tipagem Bacteriana/métodos , Mycobacterium/isolamento & purificação , Escarro/microbiologia , Adolescente , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Mali , Microscopia/métodos , Mycobacterium/classificação , Mycobacterium/efeitos dos fármacos , Razão de Chances , Estudos Prospectivos , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Adulto Jovem
10.
Fed Pract ; 34(8): 18-25, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-29200807

RESUMO

The U.S. response to the Ebola epidemic resulted in many federal agencies assessing their ability to respond to global threats and improve the efficiency of humanitarian efforts.

11.
BMC Res Notes ; 10(1): 561, 2017 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-29110699

RESUMO

BACKGROUND: Drug resistant tuberculosis presents a major public health challenge. CASE PRESENTATION: We present here the first two patients diagnosed with extensively drug resistant tuberculosis in Bamako, Mali. Genotypic findings suggest possible nosocomial transmission from the first patient to the second one, resulting in superinfection of the second patient. After being diagnosed with extensively drug resistant tuberculosis in August 2016, the patients only started receiving appropriate treatment 10 months later. CONCLUSION: The identification of these patients highlights the need for improved diagnostic and treatment algorithms for better surveillance and management of drug resistance in Mali. In the interest of these as well as future patients suffering from resistant tuberculosis, all steps recommended for programmatic management of drug resistant tuberculosis must be urgently prioritized in order to strengthen the multidrug resistant tuberculosis program.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Adulto , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Feminino , Humanos , Mali/epidemiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/fisiologia
12.
Int J Mycobacteriol ; 6(4): 379-386, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29171452

RESUMO

BACKGROUND: To identify strains of Mycobacterium tuberculosis complex (MTBc) circulating in Bamako region during the past 10 years. METHODS: From 2006 to 2016, we conducted a cross-sectional study to identify with spoligotyping, clinical isolates from tuberculosis (TB)-infected patients at different stages of their treatments in Bamako, Mali. RESULTS: Among the 904 suspected TB patients included in the study and thereafter tested in our BSL-3 laboratory, 492 (54.4%) had MTBc and therefore underwent spoligotyping. Overall, three subspecies, i.e., MTB T1 (31.9%) and MTB LAM10 (15.3%) from lineage 4 and M. africanum 2 (16.8%) from lineage 6 were the leading causes of TB in Bamako region during the past 10 years. Other spoligotypes such as MTB T3, MTB Haarlem 2, MTB EAI3, and MTB family 33 were also commonly seen from 2010 to 2016. CONCLUSION: This study showed a high genetic diversity of strains isolated in Bamako region and highlights that M. tuberculosis T1 strain was the most prevalent. Furthermore, the data indicate an increasing proportion of primary drug resistance overtime in Bamako.


Assuntos
Técnicas de Tipagem Bacteriana , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Filogenia , Tuberculose/microbiologia , Adolescente , Adulto , Idoso , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Criança , Pré-Escolar , Estudos Transversais , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Mali/epidemiologia , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Sequências Repetitivas de Ácido Nucleico/genética , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Adulto Jovem
13.
J Breath Res ; 10(3): 036012, 2016 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-27532494

RESUMO

Detection of bacterial urease activity has been utilized successfully to diagnose Helicobacter pylori (H. pylori). While Mycobacterium tuberculosis (M. tuberculosis) also possesses an active urease, it is unknown whether detection of mycobacterial urease activity by oral urease breath test (UBT) can be exploited as a rapid point of care biomarker for tuberculosis (TB) in humans. We enrolled 34 individuals newly diagnosed with pulmonary TB and 46 healthy subjects in Bamako, Mali and performed oral UBT, mycobacterial sputum culture and H. pylori testing. Oral UBT had a sensitivity and specificity (95% CI) of 70% (46-88%) and 11% (3-26%), respectively, to diagnose culture-confirmed M. tuberculosis disease among patients without H. pylori, and 100% sensitivity (69-100%) and 11% specificity (3-26%) to diagnose H. pylori among patients without pulmonary TB. Stool microbiome analysis of controls without TB or H. pylori but with positive oral UBT detected high levels of non-H. pylori urease producing organisms, which likely explains the low specificity of oral UBT in this setting and in other reports of oral UBT studies in Africa.


Assuntos
Testes Respiratórios/métodos , Fezes/microbiologia , Helicobacter pylori/enzimologia , Microbiota , Mycobacterium tuberculosis/enzimologia , Ureia/análise , Urease/metabolismo , Adulto , Demografia , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Masculino , Mali , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tuberculose/diagnóstico , Urease/genética , Adulto Jovem
14.
PLoS One ; 10(4): e0121843, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25856495

RESUMO

BACKGROUND: Short-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents. METHODS AND FINDINGS: A total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease (POD) and grade 4, potentially life-threatening events were also ascertained. CD4+ count and viral load were measured every 3 to 6 months. Poisson regression was used to compare event rates by latest CD4+ count (<50, 50-99, 100-199, 200-349, 350-499, 500+) with a focus on upper three strata, and to estimate relative risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm3. During follow-up over 70% were prescribed ART. Over follow-up 1,226 participants died; rates ranged from 57.6 (< 50 cells) to 0.8 (500+ cells) per 100 person years (py). Compared to those with latest CD4+ 200-349 (2.2/100 py), death rates were significantly lower (p<0.001), as expected, for those with 350-499 (0.9/100 py) and with 500+ cells (0.8/100 py). The composite outcome of death, POD or grade 4 events occurred in 2,302 participants (4,045 events); rates were similar in higher CD4+ count strata (9.4 for 350-499 and 7.9 for 500+ cells) and lower than those with counts 200-349 cells (13.5) (p<0.001). For those with latest CD4+ 350+ cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events. CONCLUSION: Rates of morbidity and mortality are lowest among those with CD4+ count of 350 or higher and rates do not differ for those with counts of 350-499 versus 500+ cells. Grade 4 events are the predominant morbidity for participants with CD4+ counts of 350+ cells.


Assuntos
Contagem de Linfócito CD4/estatística & dados numéricos , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Militares/estatística & dados numéricos , Morbidade/tendências , Antirretrovirais/uso terapêutico , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Humanos , Estudos Longitudinais , Análise de Regressão , África do Sul/epidemiologia
15.
Mil Med ; 168(9): 729-32, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14529248

RESUMO

The U.S. uniformed services frequently respond to natural and man-made disasters worldwide. Disaster management and humanitarian assistance has been a major focus of military medicine for well over a decade. Training for these missions is a priority for the U.S. military, specifically as a result of the Gulf War. The Medical Humanitarian Assistance Course for advanced practice nurses is a course available to train advanced practice nurses in disaster management and humanitarian assistance. This article will describe the evolution, design, format, and implementation of the Medical Humanitarian Assistance Course.


Assuntos
Planejamento em Desastres , Militares , Enfermeiros Anestesistas , Profissionais de Enfermagem , Socorro em Desastres , Altruísmo , Competência Clínica , Humanos , Estados Unidos
16.
J AIDS Clin Res ; 5(12)2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26225217

RESUMO

As globalization progressively connects and impacts the health of people across the world, collaborative research partnerships provide mutual advantages by sharing knowledge and resources to address locally and globally relevant scientific and public health questions. Partnerships undertaken for scientific research are similar to business collaborations in that they require attention to partner systems, whether local, international, political, academic, or non-academic. Scientists, like diplomats or entrepreneurs, are representatives of their field, culture, and country and become obligatory agents in health diplomacy. This role significantly influences current and future collaborations with not only the immediate partner but with other in country partners as well. Research partnerships need continuous evaluation of the collaboration's productivity, perspectives of all partners, and desired outcomes for success to avoid engaging in "research tourism", particularly in developing regions. International engagement is a cornerstone in addressing the impact of infectious diseases globally. Global partnerships are strategically aligned with national, partner and global health priorities and may be based on specific requests for assistance from the partnering country governments. Here we share experiences from select research collaborations to highlight principles that we have found key in building long-term relationships with collaborators and in meeting the aim to address scientific questions relevant to the host country and strategic global health initiatives.

18.
PLoS One ; 7(3): e24243, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22448211

RESUMO

BACKGROUND: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART. METHODS: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels. RESULTS: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9-6.7) for hsCRP, 2.6 (95%CI 1.4-4.9) for D-dimer, and 3.8 (95% CI: 1.8-7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001). CONCLUSIONS: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted. TRIAL REGISTRATION: Parent study: ClinicalTrials.gov NCT00342355.


Assuntos
Terapia Antirretroviral de Alta Atividade , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , Infecções por HIV/mortalidade , HIV/fisiologia , Inflamação/diagnóstico , Adulto , Linfócitos T CD4-Positivos , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , HIV/efeitos dos fármacos , Infecções por HIV/complicações , Infecções por HIV/virologia , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Prognóstico , África do Sul , Taxa de Sobrevida , Carga Viral
19.
Antivir Ther ; 16(4): 605-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21685549

RESUMO

BACKGROUND: Lactic acidosis (LA) is a potentially life-threatening complication of antiretroviral (ARV) therapy. Few randomized prospective studies have compared LA between different ARV regimens. METHODS: Characterization of cases of LA (serum lactate >5 mmol/l and arterial pH<7.35 or bicarbonate <20 mmol/l) and symptomatic hyperlactataemia (SH; serum lactate >2.2 mmol/l and symptoms) was made in a randomized open-label 2×2 factorial study of stavudine/lamivudine (d4T/3TC)-based versus didanosine/zidovudine-based therapy and lopinavir/ritonavir-based versus efavirenz (EFV)-based therapy in 1,771 HIV-infected adults initiating therapy between 2004 and 2008. RESULTS: The LA incident rate was 3.5/1,000 person-years (95% CI 1.8-5.9), and for combined LA/SH was 11.0/1,000 person-years (95% CI 7.9-14.9). There were two deaths (15% mortality) among 13 LA cases; all 11 survivors experienced symptom resolution and started new ARV regimens. LA cases were more likely to be female (OR 7.19, 95% CI 1.84-40.75; P=0.001) and had a higher body mass index (BMI; P<0.0001) compared with non-cases. There was no increase in LA according to ARV regimen, age or CD4(+) T-cell count at randomization. When combined, LA/SH cases (n=41) were more often female (OR 4.76, 95% CI 2.36-10.08; P<0.0001), had increased BMI (P<0.0001), were more likely to be assigned d4T/3TC (OR 3.17, 95% CI 1.50-7.28; P=0.001) and were more likely to be assigned EFV (OR 2.18, 95% CI 1.08-4.61; P=0.026). CONCLUSIONS: Female sex and increased BMI were associated with severe LA in this large randomized trial of first-line ARV in South Africa. While female sex, increased BMI and d4T are previously described risk factors for the development of clinically significant lactate elevations, the independent risk associated with EFV is a novel observation warranting further investigation.


Assuntos
Acidose Láctica/epidemiologia , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Lactatos/sangue , Inibidores da Transcriptase Reversa/efeitos adversos , Acidose Láctica/mortalidade , Adulto , Alcinos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Ciclopropanos , Quimioterapia Combinada , Feminino , Humanos , Incidência , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêutico , África do Sul/epidemiologia , Estavudina/administração & dosagem , Estavudina/efeitos adversos , Estavudina/uso terapêutico , Resultado do Tratamento
20.
AIDS ; 25(14): 1727-35, 2011 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-21716078

RESUMO

OBJECTIVE: To examine HIV and hepatitis B virus (HBV)-related outcomes in HIV/HBV-coinfected participants in the PHIDISA II study by use of HBV-active vs. non-HBV-active antiretroviral therapy (ART). DESIGN AND METHODS: PHIDISA II was a randomized study of ART therapy in HIV-infected adults employing zidovudine along with didanosine, or lamivudine along with stavudine in a factorial 2x2 design. HIV/HBV-coinfected participants by randomization received HBV-active or non-HBV-active ART. The following outcomes of interest were examined: immunological recovery and HIV RNA suppression; hepatic flare; HBV DNA suppression; and mortality. RESULTS: HIV/HBV coinfection was present in 106 of 1771 (6%) of participants. Participants with HIV/HBV coinfection were more likely to be men, and have higher baseline alanine aminotransferase, lower albumin, and lower platelets than those with HIV monoinfection. Median CD4 cell gain and HIV RNA suppression was similar across all groups. Hepatic flare was observed in 9.4% of coinfected and 0.02% monoinfected participants. HBV DNA suppression (<55 IU/ml) at week 48 was observed in only 33% of those on lamivudine vs. 13% in those on no HBV-active drugs (P = 0.13). Mortality over follow-up was significantly greater in coinfected (17%) than monoinfected (11%) participants (P = 0.04). CONCLUSION: In summary, the use of lamivudine-containing ART in HIV/HBV participants in PHIDISA II resulted in little additional benefit over that of ART itself and failed to impact on the greater mortality in this group. These data provide strong support for recent guidelines advocating the use of tenofovir in all HIV-HBV-coinfected individuals initiating ART.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antirretrovirais/farmacologia , Didanosina/farmacologia , HIV-1/efeitos dos fármacos , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Lamivudina/farmacologia , Estavudina/farmacologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/fisiopatologia , Adulto , África Austral , Antirretrovirais/administração & dosagem , Contagem de Linfócito CD4 , Didanosina/administração & dosagem , Feminino , Hepatite B Crônica/mortalidade , Hepatite B Crônica/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Lamivudina/administração & dosagem , Masculino , Estavudina/administração & dosagem , Resultado do Tratamento
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