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1.
J Immunol Methods ; 496: 113096, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242653

RESUMO

Serology or antibody tests for COVID-19 are designed to detect antibodies (mainly Immunoglobulin M (IgM) and Immunoglobulin G (IgG) produced in response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) infection. In this study, 30 lateral flow immunoassays were tested using serum or plasma from patients with confirmed SARS CoV-2 infection. Negative serological controls were accessed from a well-characterised bank of sera which were stored prior to February 2020. Operational characteristics and ease of use of the assays are reported. 4/30 (13%) of kits (Zheihang Orient Gene COVID-19 IgG/IgM, Genrui Novel Coronavirus (2019-nCoV) IgG/IgM, Biosynex COVID-19 BSS IgG/IgM, Boson Biotech 2019-nCoV IgG/IgM) were recommended for SAHPRA approval based on kit sensitivity. Of these, only the Orientgene was recommended by SAHPRA in August 2020 for use within the approved national testing algorithm while the remaining three received limited authorization for evaluation. All kits evaluated work on the same basic principle of immunochromatography with minor differences noted in the shape and colour of cartridges, the amount of specimen volume required and the test duration. Performance of the lateral flow tests were similar to sensitivities and specificities reported in other studies. The cassettes of the majority of kits evaluated (90%) detected both IgG and IgM. Only 23% of kits evaluated contained all consumables required for point-of-care testing. The study highlights the need for thorough investigation of kits prior to implementation.


Assuntos
Anticorpos Antivirais/isolamento & purificação , Teste Sorológico para COVID-19/instrumentação , COVID-19/diagnóstico , Imunoensaio/instrumentação , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Teste Sorológico para COVID-19/estatística & dados numéricos , Humanos , Imunoensaio/estatística & dados numéricos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Imunoglobulina M/isolamento & purificação , Testes Imediatos/estatística & dados numéricos , RNA Viral/sangue , RNA Viral/isolamento & purificação , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade
2.
PLoS One ; 16(6): e0252317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34161348

RESUMO

Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) has been identified as the causative agent for causing the clinical syndrome of COVID -19. Accurate detection of SARS-CoV-2 infection is not only important for management of infected individuals but also to break the chain of transmission. South Africa is the current epicenter of SARS-CoV-2 infection in Africa. To optimize the diagnostic algorithm for SARS-CoV-2 in the South African setting, the study aims to evaluate the diagnostic performance of the EUROIMMUN Anti-SARS-CoV-2 assays. This study reported the performance of EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples targeting the recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Samples were collected from 391 individuals who had tested positive for SARS-CoV-2 and 139 SARS CoV-2 negative controls. Samples were stratified by number of days' post-PCR diagnosis and symptoms. The sensitivity of EUROIMMUN IgG was 64.1% (95% CI: 59.1-69.0%) and 74.3% (95% CI: 69.6-78.6%) for IgA and the specificity was lower for IgA [84.2% (95% CI: 77-89.2%)] than IgG [95.2% (95% CI: 90.8-98.4%)]. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay sensitivity was higher for IgA but low for IgG and improved for both assays in symptomatic individuals and at later timepoints post PCR diagnosis.


Assuntos
Teste Sorológico para COVID-19/métodos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste de Ácido Nucleico para COVID-19/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Sensibilidade e Especificidade , África do Sul
4.
N Engl J Med ; 384(18): 1705-1718, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33951360

RESUMO

BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.).


Assuntos
Antibióticos Antituberculose/administração & dosagem , Antituberculosos/uso terapêutico , Moxifloxacina/administração & dosagem , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/administração & dosagem , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Antibióticos Antituberculose/efeitos adversos , Antituberculosos/efeitos adversos , Criança , Intervalos de Confiança , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Moxifloxacina/efeitos adversos , Rifampina/efeitos adversos , Adulto Jovem
5.
Lancet Glob Health ; 9(5): e628-e638, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33865471

RESUMO

BACKGROUND: Facility-based, multimonth dispensing of antiretroviral therapy (ART) for HIV could reduce burdens on patients and providers and improve retention in care. We assessed whether 6-monthly ART dispensing was non-inferior to standard of care and 3-monthly ART dispensing. METHODS: We did a pragmatic, cluster-randomised, unblinded, non-inferiority trial (INTERVAL) at 30 health facilities in Malawi and Zambia. Eligible participants were aged 18 years or older, HIV-positive, and were clinically stable on ART. Before randomisation, health facilities (clusters) were matched on the basis of country, ART cohort size, facility type (ie, hospital vs health centre), and region or province. Matched clusters were randomly allocated (1:1:1) to standard of care, 3-monthly ART dispensing, or 6-monthly ART dispensing using a simple random allocation sequence. The primary outcome was retention in care at 12 months, defined as the proportion of patients with less than 60 consecutive days without ART during study follow-up, analysed by intention to treat. A 2·5% margin was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03101592. FINDINGS: Between May 15, 2017, and April 30, 2018, 9118 participants were randomly assigned, of whom 8719 participants (n=3012, standard of care group; n=2726, 3-monthly ART dispensing group; n=2981, 6-monthly ART dispensing group) had primary outcome data available at 12 months and were included in the primary analysis. The median age of participants was 42·7 years (IQR 36·1-49·9) and 5774 (66·2%) of 8719 were women. The primary outcome was met by 2478 (82·3%) of 3012 participants in the standard of care group, 2356 (86·4%) of 2726 participants in the 3-monthly ART dispensing group, and 2729 (91·5%) of 2981 participants in the 6-monthly ART dispensing group. After adjusting for clustering, for retention in care at 12 months, the 6-monthly ART dispensing group was non-inferior to the standard of care group (percentage-point increase 9·1 [95% CI 0·9-17·2]) and to the 3-monthly ART dispensing group (5·0% [1·0-9·1]). INTERPRETATION: Clinical visits with ART dispensing every 6 months was non-inferior to standard of care and 3-monthly ART dispensing. 6-monthly ART dispensing is a promising strategy for the expansion of ART provision and achievement of HIV treatment targets in resource-constrained settings. FUNDING: US Agency for International Development.


Assuntos
Infecções por HIV/tratamento farmacológico , Adulto , Fármacos Anti-HIV/uso terapêutico , Análise por Conglomerados , Esquema de Medicação , Feminino , Humanos , Malaui , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Zâmbia
6.
Glob Health Action ; 14(1): 1865625, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491593

RESUMO

The WHO developed a generic 'TB patient cost survey' tool and a standardized approach to assess the direct and indirect costs of TB incurred by patients and their households, estimate the proportion of patients experiencing catastrophic costs, and measure the impact of interventions to reduce patient costs. While the generic tool is a facility-based cross-sectional survey, this standardized approach needs to be adapted for longitudinal studies. A longitudinal approach may overcome some of the limitations of a cross-sectional design and estimate the economic burden of TB more precisely. We describe the process of creating a longitudinal instrument and its application to the TB Sequel study, an ongoing multi-country, multi-center observational cohort study. We adapted the cross-sectional WHO generic TB patient cost survey instrument for the longitudinal study design of TB Sequel and the local context in each study country (South Africa, Mozambique, Tanzania, and The Gambia). The generic instrument was adapted for use at enrollment (start of TB treatment; Day 0) and at 2, 6, 12 and 24 months after enrollment, time points intended to capture costs incurred for diagnosis, during treatment, at the end of treatment, and during long-term follow-up once treatment has been completed. These time points make the adapted version suitable for use in patients with either drug-sensitive or drug-resistant TB. Using the adapted tool provides the opportunity to repeat measures and make comparisons over time, describe changes that extend beyond treatment completion, and link cost survey data to treatment outcomes and post-TB sequelae. Trial registration: ClinicalTrials.gov: NCT032516 August 1196, 2017. Abbreviations: DOTS: Directly observed treatment, short-course; DR-TB: Drug-resistant tuberculosis; MDR-TB: Multi-drug resistant tuberculosis; NTP: National Tuberculosis Programme; TB: Tuberculosis; USD: United States Dollar; WHO: World Health Organization.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Efeitos Psicossociais da Doença , Estudos Transversais , Gâmbia , Custos de Cuidados de Saúde , Humanos , Estudos Longitudinais , Moçambique , África do Sul , Tanzânia , Tuberculose/tratamento farmacológico , Organização Mundial da Saúde
7.
Clin Infect Dis ; 72(9): 1642-1644, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32628744

RESUMO

Countries such as South Africa have limited intensive care unit (ICU) capacity to handle the expected number of patients with COVID-19 requiring ICU care. Remdesivir can prevent deaths in countries such as South Africa by decreasing the number of days people spend in ICU, therefore freeing up ICU bed capacity.


Assuntos
COVID-19 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , COVID-19/tratamento farmacológico , Humanos , Unidades de Terapia Intensiva , SARS-CoV-2 , África do Sul/epidemiologia
8.
J Viral Hepat ; 28(1): 147-158, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32935438

RESUMO

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight-based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co-infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro-costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow-up. SVR was achieved in 680/803 (84.6%) by intention-to-treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non-PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real-world estimate of $1250. High SVR rates were achieved for non-PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real-world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population.

9.
medRxiv ; 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32995824

RESUMO

Background South Africa recently experienced a first peak in COVID-19 cases and mortality. Dexamethasone and remdesivir both have the potential to reduce COVID-related mortality, but their cost-effectiveness in a resource-limited setting with scant intensive care resources is unknown. Methods We projected intensive care unit (ICU) needs and capacity from August 2020 to January 2021 using the South African National COVID-19 Epi Model. We assessed cost-effectiveness of 1) administration of dexamethasone to ventilated patients and remdesivir to non-ventilated patients, 2) dexamethasone alone to both non-ventilated and ventilated patients, 3) remdesivir to non-ventilated patients only, and 4) dexamethasone to ventilated patients only; all relative to a scenario of standard care. We estimated costs from the healthcare system perspective in 2020 USD, deaths averted, and the incremental cost effectiveness ratios of each scenario. Results Remdesivir for non-ventilated patients and dexamethasone for ventilated patients was estimated to result in 1,111 deaths averted (assuming a 0-30% efficacy of remdesivir) compared to standard care, and save $11.5 million. The result was driven by the efficacy of the drugs, and the reduction of ICU-time required for patients treated with remdesivir. The scenario of dexamethasone alone to ventilated and non-ventilated patients requires additional $159,000 and averts 1,146 deaths, resulting in $139 per death averted, relative to standard care. Conclusions The use of dexamethasone for ventilated and remdesivir for non-ventilated patients is likely to be cost-saving compared to standard care. Given the economic and health benefits of both drugs, efforts to ensure access to these medications is paramount.

10.
J Acquir Immune Defic Syndr ; 85(3): 280-291, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32665460

RESUMO

BACKGROUND: Lesotho adopted the test-and-treat approach for HIV treatment in June 2016, which increased antiretroviral treatment (ART) clinic volume. We evaluated community-based vs. facility-based differentiated models of multimonth dispensing of ART among stable HIV-infected adults in Lesotho. METHODS: Thirty facilities were randomized to 3 arms, facility 3-monthly ART (3MF) (control), community ART groups (3MC), and 6-monthly community distribution points (6MCD). We estimated risk differences (RDs) between arms using population-averaged generalized estimating equations, controlling for baseline imbalances and specifying for clustering. The primary outcome was retention in ART care by intention-to-treat and virologic suppression as a secondary outcome (ClinicalTrials.gov: NCT03438370). RESULTS: A total of 5,336 participants were enrolled, with 1898, 1558, and 1880 in 3MF, 3MC, and 6MCD, respectively. Retention in ART care was not different across arms and achieved the prespecified noninferiority limit (-3.25%) between 3MC vs. 3MF (control); 6MCD vs. 3MF; and 6MCD vs. 3MC, adjusted RD = -0.1% [95% confidence interval (CI): -1.6% to 1.5%], adjusted RD = -1.3% (95% CI: -3.0% to 0.5%), and adjusted RD = -1.2% (95% CI: -2.9% to 0.5%), respectively. After 12 months, 98.6% (n = 1503), 98.1% (n = 1126), and 98.3% (n = 1285) were virally load (VL) suppressed in 3MF, 3MC, and 6MCD, respectively. There were no differences in VL between 3MC vs. control and 6MCD vs. control, risk ratio (RR) = 1.00 (95% CI: 0.98 to 1.01) and RR = 1.00 (95% CI: 0.98 to 1.01), respectively. CONCLUSIONS: There were no differences in retention and VL suppression for stable HIV-infected participants receiving multimonth dispensing of ART within community-based differentiated models when compared with the facility-based standard-of-care model.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Fármacos Anti-HIV/economia , Análise por Conglomerados , Prescrições de Medicamentos , Feminino , Custos de Cuidados de Saúde , Instalações de Saúde , Acesso aos Serviços de Saúde , Humanos , Lesoto , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Carga Viral , Adulto Jovem
11.
BMC Infect Dis ; 20(1): 320, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366227

RESUMO

BACKGROUND: Rapid diagnostic tests (RDTs) are a cornerstone of HIV diagnosis and rely on good quality processing and interpretation, particularly in the era of test and treat. The Deki Reader (Fio Corporation®, Toronto, Ontario, Canada) is a portable device designed specifically for analysing RDTs and was selected for evaluation in South Africa in the context of HIV RDT analysis. METHODS: This study consisted of a laboratory evaluation and two-part field evaluation of the Deki Reader v100, covering two RDT testing algorithms, and an evaluation of the continuous quality monitoring through the Fionet™ web portal. Based on user feedback from the field evaluation, the device underwent hardware and software redesign, and the Deki Reader v200 was evaluated in the laboratory. Ethics approval for this evaluation was obtained from the University of the Witwatersrand Human Research Ethics Committee: M150160. RESULTS: The intra- and inter-device laboratory precision of the Deki Reader v100 were 98.3 and 99.2% respectively, and 99.3 and 100% for the Deki Reader v200. The laboratory concordances compared to standard-of-care reporting were 99.5 and 98.0% for the two respective models, while sensitivity and specificity were 99.5 and 99.4% for the Deki Reader V100 and 100 and 93.1% for the Deki Reader V200 respectively. Screening and confirmatory concordances in the field were 99.3 and 96.5% under algorithm 1 and 99.7 and 100% under algorithm 2. Sensitivity and specificity for the field evaluation were 99.8 and 97.7%. Overall robustness of the device was acceptable and continuous quality monitoring through Fionet™ was feasible. CONCLUSIONS: The Deki Reader provides an option for improved and reliable quality assessment for rapid diagnosis of HIV using RDTs to enhance the quality of healthcare at the point-of-care. However, the introduction of new RDTs and modification of current algorithms necessitates ongoing and agile RDT reader adjustments, which will require cost modelling to ensure sustainability of devices implemented into national HIV programs.


Assuntos
Sorodiagnóstico da AIDS/instrumentação , Testes Diagnósticos de Rotina/instrumentação , Ensaio de Imunoadsorção Enzimática/instrumentação , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , HIV-1/imunologia , HIV-2/imunologia , Sorodiagnóstico da AIDS/métodos , Algoritmos , Testes Diagnósticos de Rotina/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Infecções por HIV/virologia , Humanos , Programas de Rastreamento/métodos , Aplicativos Móveis , Sistemas Automatizados de Assistência Junto ao Leito , Prevalência , Sensibilidade e Especificidade , África do Sul/epidemiologia
12.
AIDS ; 34(5): 681-686, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972605

RESUMO

OBJECTIVE: HIV cure research urgently needs to identify pre-analytic treatment interruption (ATI) biomarkers of time-to-viral-rebound and viral setpoint to mitigate the risk of ATI and accelerate development of a cure. We previously reported that galactosylated IgG glycans, G2, negatively correlate with cell-associated HIV DNA and RNA during antiretroviral therapy (ART). We hypothesized that this and other plasma glycomic traits can predict time-to-viral-rebound and viral setpoint upon ART cessation. DESIGN: We profiled the circulating glycomes (plasma and bulk IgG) of two geographically distinct cohorts: Philadelphia Cohort - 24 HIV-infected, ART-suppressed individuals who had participated in an open-ended ATI study without concurrent immunomodulatory agents. Johannesburg Cohort - 23 HIV-infected, ART-suppressed individuals who had participated in a 2-week ATI. METHODS: Capillary electrophoresis and lectin microarray were used for glycomic analyses. Cox proportional-hazards model and log-rank test were used for statistical analyses. RESULTS: Higher pre-ATI levels of the IgG glycan, G2, were significantly associated with a longer time-to-viral-rebound (hazard ratio = 0.12, P = 0.05). In addition to G2, we identified several predictive glycomic traits in plasma, for example, levels of FA2BG1, a non-sialylated, core-fucosylated glycan, associated with a longer time-to-viral-rebound (hazard ratio = 0.023, P = 0.05), whereas FA2G2S1, a sialylated glycan, associated with a shorter time-to-viral-rebound (hazard ratio = 24.1, P = 0.028). Additionally, pre-ATI plasma glycomic signatures associated with a lower viral setpoint, for example, T-antigen (Galß1-3GalNAc) (r = 0.75, P = 0.0007), or a higher viral setpoint, for example, polylactosamine (r = -0.58, P = 0.01). These results were initially validated in the Johannesburg Cohort. CONCLUSION: We describe first-in-class, non-invasive, plasma and IgG glycomic biomarkers that inform time-to-viral-rebound and viral setpoint in two geographically distinct cohorts.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Glicômica , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Biomarcadores , Infecções por HIV/sangue , HIV-1/genética , Humanos , RNA Viral/sangue , África do Sul , Carga Viral/efeitos dos fármacos , Replicação Viral
13.
AIDS ; 34(3): 475-479, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31764076

RESUMO

BACKGROUND: Little is known about the proportion of HIV-positive clients on antiretroviral therapy (ART) who meet stability criteria for differentiated service delivery (DSD) models. We report the proportion of ART clients meeting stability criteria as part of screening for a randomized trial of multimonth dispensing in Malawi and Zambia. METHODS: For a DSD trial now underway, we screened HIV-positive clients aged at least 18 years presenting for HIV treatment in 30 adult ART clinics in Malawi and Zambia to determine eligibility for DSD. Stability was defined as on first-line ART (efavirenz/tenofovir/lamivudine) for at least 6 months, no ART side effects, no toxicity or infectious complications, no noncommunicable diseases being treated in ART clinic, no lapses in ART adherence in the prior 6 months (>30 days without taking ART), and if female, not pregnant or breastfeeding. RESULTS: In total, 3465 adult ART clients were approached between 10 May 2017 and 30 April 2018 (Malawi: 1680; Zambia: 1785). Of the 2938 who answered screening questions (Malawi: 1527; Zambia: 1411), 2173 (73.5%) met criteria for DSD eligibility (Malawi: 72.8%; Zambia: 74.3%). The most common reasons for ineligibility were being on ART less than 6 months (9.6%) and a regimen other than standard first-line (7.9%). CONCLUSION: Approximately three-quarters of all adult clients presenting at ART clinics in Malawi and Zambia were eligible for DSD using a typical definition of stability. High uptake of DSD models by eligible clients would have a major impact on the infrastructure and the allocation of HIV treatment resources.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Definição da Elegibilidade , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Malaui , Ensaios Clínicos Controlados Aleatórios como Assunto , Tenofovir/uso terapêutico , Zâmbia
14.
AIDS ; 33(13): 2049-2059, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577571

RESUMO

OBJECTIVE: Obesity is a major long-term concern in HIV-positive patients due to the pathogenic link between obesity and noncommunicable chronic diseases (NCDs). We aim to characterize changes in BMI over time on antiretroviral therapy (ART) and investigate the association between weight gain and survival in South Africa. DESIGN AND METHODS: A prospective cohort study among HIV-positive adults on first-line ART between April 2004 and 2015 in Johannesburg, South Africa. We used latent-class growth modelling (adjusted for age, sex and CD4 cell count) to identify groups of individuals with similar patterns of change in BMI over time. RESULTS: Eleven thousand, two hundred and sixty-three patients were included. The best fit model involved two linear and two quadratic trajectories. Thirty-five percent of patients were categorized into group one (mean BMI at ART initiation, 20.4 kg/m; mean BMI after 8 years of follow-up, 20.9 kg/m), 38% into group two (24.5-26.2 kg/m), 21% into group three (29.5-32.6 kg/m) and 6% into group four (36.5-40.0 kg/m). Over the 8 years of follow-up, 6% of our cohort went down in BMI standard category, while 45% went up. The largest increase occurred in the first 12 months on ART. In years 2 through 8, we saw a more gradual increase in BMI. CONCLUSION: The largest gain in BMI in HIV patients occurred in the first year on ART. During follow-up, over 50% of our population changed BMI categories putting them at an increased risk for NCDs. Consistent counselling on nutritional and lifestyle changes could help improve ART patients' long-term health outcomes.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Índice de Massa Corporal , Infecções por HIV/complicações , Obesidade/complicações , Adolescente , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Obesidade/virologia , Estudos Prospectivos , Fatores de Risco , África do Sul/epidemiologia , Análise de Sobrevida , Ganho de Peso , Adulto Jovem
15.
Lancet HIV ; 6(7): e438-e446, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31160268

RESUMO

BACKGROUND: Safer conception strategies empower individuals trying to conceive to minimise HIV transmission risk to partners and potential children; however, effectiveness data are scarce. We aimed to assess adoption of safer conception methods and HIV and pregnancy outcomes from Sakh'umndeni, a novel safer conception service in South Africa. METHODS: In this prospective cohort study, the Sakh'umndeni clinical cohort at Witkoppen Cinic in Johannesburg (South Africa) enrolled adults aged at least 18 years who were trying to conceive and in relationships with an HIV-positive partner. Couples who were pregnant at enrolment or had been previously diagnosed as infertile were excluded. Participants received safer conception care by a nurse, including antiretroviral therapy (ART) for HIV-positive partners, pre-exposure prophylaxis (PrEP) for HIV-negative partners, counselling around timed condomless sex, or syringes for self-insemination. Primary outcomes were pregnancy incidence and HIV transmission to partners and infants. We estimated time to first pregnancy using Kaplan-Meier curves; pregnancy and HIV incidence were estimated as events per person-years of risk. FINDINGS: Between July 16, 2013, and April 5, 2017, 526 individuals (334 women and 192 men) from 334 partnerships enrolled. 162 (48%) of 334 couples were serodifferent, 149 (45%) were HIV-positive seroconcordant, and 23 (7%) were an HIV-positive woman and an unknown status male partner. At enrolment, 176 (61%) of 287 HIV-positive women and 60 (46%) of 131 HIV-positive men were virally suppressed (<50 copies per mL). Among the safer conception strategies, ART was initiated by 73 (91%) of 80 HIV-positive participants not on ART and PrEP was initiated by 28 (28%) of 101 HIV-negative participants. 2719 follow-up visits were completed, and 99 pregnancies were observed in 89 women. Pregnancy incidence was 41·2 per 100 person-years (95% CI 33·4-50·7); 25 (28%) of 89 pregnancies with a known outcome were miscarried or terminated because of risk to the mother. Pregnancy incidence was 79·0 per 100 person-years (95% CI 49·8-125·4) among HIV-negative women and 36·7 per 100 person-years (29·1-46·3) among HIV-positive women. At the time of pregnancy, viral suppression among women was high (68 [87%] of 78 women had viral loads of <50 copies per mL and 77 [99%] had viral loads of <1000 copies per mL). No horizontal or vertical HIV transmission events were observed. INTERPRETATION: Safer conception strategies empowered couples to safely conceive. Pregnancy incidence among service users was high. Integration of safer conception counselling could promote HIV prevention and linkage to care. FUNDING: US Agency for International Development; UJMT Consortium/Fogarty International Center, US National Institutes of Health (NIH); and Johns Hopkins University Center for AIDS Research (NIH).


Assuntos
Fertilização , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Saúde Reprodutiva , Adulto , Feminino , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Complicações Infecciosas na Gravidez/virologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Serviços de Saúde Reprodutiva , Fatores de Risco , África do Sul/epidemiologia , Carga Viral
16.
BMC Pulm Med ; 19(1): 4, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30616617

RESUMO

BACKGROUND: Up to fifty percent of microbiologically cured tuberculosis (TB) patients may be left with permanent, moderate or severe pulmonary function impairment. Very few studies have systematically examined pulmonary outcomes in patients to understand the pathophysiologic basis and long-term socio-economic consequences of this injury. The planned multi-country, multi-centre observational TB cohort study, aims to advance the understanding of the clinical, microbiological, immunological and socio-economic risk factors affecting long-term outcome of pulmonary TB. It will also determine the occurrence of reversible and irreversible socio-economic consequences to patients, their households and the health sector related to pulmonary TB disease and its treatment. METHODS: We will enrol up to 1.600 patients with drug sensitive and multidrug-resistant pulmonary TB who are treated according to the local standard of care by the respective National TB Program. Recruitment is taking place at the time of TB diagnosis at four African study clinics located in The Gambia, Mozambique, South Africa and Tanzania. The primary outcome is the proportion of TB patients with severe lung impairment measured by spirometry at 24 months after TB treatment initiation. Biological samples, including sputum, urine and blood, for studying host- and pathogenic risk factors will be collected longitudinally and examined in a nested case-control fashion. A standardized quality of life questionnaire will be used together with a novel version of WHO's generic patient cost instrument which has been adapted for the longitudinal study design. DISCUSSION: This study is an integral part of an overall strategy to fill a knowledge gap needed to improve TB treatment outcomes globally. The main scientific goal is to identify the major pathogenic mechanisms associated with poor TB treatment outcomes, so that such pathways can be interrupted to avert long term TB sequelae. National as well as supra-national stakeholders and decision makers have been integrated early in the study planning process to inform future treatment guidelines and national health policies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03251196 , August 16, 2017.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/fisiopatologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/fisiopatologia , África ao Sul do Saara/epidemiologia , Antituberculosos/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Estudos Prospectivos , Qualidade de Vida , Testes de Função Respiratória , Fatores de Risco , Espirometria , Escarro/microbiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico
17.
Clin Infect Dis ; 68(10): 1739-1746, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30137250

RESUMO

BACKGROUND: AIDS Clinical Trial Group 5199 compared neurological and neuropsychological test performance of human immunodeficiency virus type 1 (HIV-1)-infected participants in resource-limited settings treated with 3 World Health Organization-recommended antiretroviral (ART) regimens. We investigated the impact of tuberculosis (TB) on neurological and neuropsychological outcomes. METHODS: Standardized neurological and neuropsychological examinations were administered every 24 weeks. Generalized estimating equation models assessed the association between TB and neurological/neuropsychological performance. RESULTS: Characteristics of the 860 participants at baseline were as follows: 53% female, 49% African; median age, 34 years; CD4 count, 173 cells/µL; and plasma HIV-1 RNA, 5.0 log copies/mL. At baseline, there were 36 cases of pulmonary, 9 cases of extrapulmonary, and 1 case of central nervous system (CNS) TB. Over the 192 weeks of follow-up, there were 55 observations of pulmonary TB in 52 persons, 26 observations of extrapulmonary TB in 25 persons, and 3 observations of CNS TB in 2 persons. Prevalence of TB decreased with ART initiation and follow-up. Those with TB coinfection had significantly poorer performance on grooved pegboard (P < .001) and fingertapping nondominant hand (P < .01). TB was associated with diffuse CNS disease (P < .05). Furthermore, those with TB had 9.27 times (P < .001) higher odds of reporting decreased quality of life, and had 8.02 times (P = .0005) higher odds of loss of productivity. CONCLUSIONS: TB coinfection was associated with poorer neuropsychological functioning, particularly the fine motor skills, and had a substantial impact on functional ability and quality of life. CLINICAL TRIALS REGISTRATION: NCT00096824.


Assuntos
Disfunção Cognitiva/diagnóstico , Coinfecção/complicações , Infecções por HIV/complicações , Recursos em Saúde/provisão & distribuição , Doenças do Sistema Nervoso/diagnóstico , Tuberculose/complicações , Adulto , Disfunção Cognitiva/microbiologia , Disfunção Cognitiva/virologia , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , HIV-1 , Humanos , Internacionalidade , Estudos Longitudinais , Masculino , Destreza Motora , Doenças do Sistema Nervoso/microbiologia , Doenças do Sistema Nervoso/virologia , Testes Neuropsicológicos , Estudos Prospectivos , Qualidade de Vida , Tuberculose/virologia
18.
Carcinogenesis ; 40(2): 225-233, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-30364933

RESUMO

Identification of factors associated with human papillomavirus (HPV) cervical histopathology or recurrence/relapse following loop electrosurgical excision procedure (LEEP) would allow for better management of the disease. We investigated whether gene signatures could (i) associate with HPV cervical histopathology and (ii) identify women with post-LEEP disease recurrence/relapse. Gene array analysis was performed on paraffin-embedded cervical tissue-isolated RNA from two cross-sectional cohorts of antiretroviral therapy (ART)-suppressed HIV+HPV+ coinfected women: (i) 55 women in South Africa recruited into three groups: high risk (HR) (-) (n = 16) and HR (+) (n = 15) HPV without cervical histopathology and HR (+) HPV with cervical intraepithelial neoplasia (CIN) grade 1/2/3 (n = 24), (ii) 28 women in Botswana with CIN2/3 treated with LEEP 12-month prior to recruitment and presenting with (n = 13) and without (n = 15) lesion recurrence/relapse (tissue was analyzed at first LEEP). Three distinct gene expression signatures identified were able to segregate: (i) HR+ HPV and CIN1/2/3, (ii) HR HPV-free and cervical histopathology-free and (iii) HR+ HPV and cervical histopathology-free. Immune activation and neoplasia-associated genes (n = 272 genes; e.g. IL-1A, IL-8, TCAM1, POU4F1, MCM2, SMC1B, CXCL6, MMP12) were a feature of cancer precursor dysplasia within HR HPV infection. No difference in LEEP tissue gene expression was detected between women with or without recurrence/relapse. In conclusion, distinctive gene signatures were associated with presence of cervical histopathology in tissues from ART-suppressed HIV+/HPV+ coinfected women. Lack of detection of LEEP tissue gene signature able to segregate subsequent post-LEEP disease recurrence/relapse indicates additional factors independent of local gene expression as determinants of recurrence/relapse.


Assuntos
Colo do Útero/patologia , Expressão Gênica/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Adulto , Antirretrovirais/farmacologia , Neoplasia Intraepitelial Cervical/tratamento farmacológico , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/efeitos dos fármacos , Colo do Útero/virologia , Estudos Transversais , Feminino , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Papillomaviridae/efeitos dos fármacos , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/virologia
19.
PLoS One ; 13(10): e0205463, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30300403

RESUMO

INTRODUCTION: Treatment success rates of rifampicin resistant (RR)/multi-drug resistant (MDR) tuberculosis (TB) in South Africa range from 43-48%, falling short of the World Health Organization's target of ≥75%. We present rates and assess predictors of attrition by 12 months on treatment. METHODS: Prospective observational cohort analysis of adults (≥18 years) initiating RR/MDR-TB treatment from 01 March 2013 to 30 September 2016. Attrition was defined as a combination of death and loss to follow-up (LTFU; treatment interruption ≥2 months) by 12 months on treatment. Predictors of attrition were identified using Cox Proportional Hazards models to estimate crude (HR) and adjusted hazard ratios (aHR) with corresponding 95% confidence intervals. RESULTS: By 12 months on treatment, 75/240 (31.3%) patients had either died (37/240; 15.4%) or been LTFU (38/240; 15.8%). Patients with moderate/severe anaemia (aHR: 2.10; 95% CI 1.00-4.39), and those who were smear positive at baseline (aHR: 2.04; 95% CI 1.01-4.12) were significantly more likely to die or be lost from care. CONCLUSION: At this outpatient DR-TB treatment site, there was a high rate of attrition halfway through the standard treatment course at 12 months of 31%. High rates of attrition by 12 months on treatment may continue during the second-half of therapy.


Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana , Rifampina/uso terapêutico , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Anemia/etiologia , Anemia/patologia , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Modelos de Riscos Proporcionais , Estudos Prospectivos , Índice de Gravidade de Doença , Tuberculose/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade , Adulto Jovem
20.
PLoS One ; 13(10): e0204020, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30281618

RESUMO

BACKGROUND: One of the key risk factors for cardiovascular disease is hypertension. Hypertension, which leads to heart attacks and strokes, already affects one billion people worldwide, making it a global public health issue. Incidence and prevalence of the condition is on the rise in low- and middle-income countries, with the biggest increase in sub-Saharan Africa and South Africa at the forefront. We examined the prevalence, incidence, predictors, treatment, and control of hypertension among HIV-positive patients on ART in a large South African observational cohort. METHODS: We conducted a prospective study of ART naïve adults initiating ART at a public sector HIV clinic in South Africa between April 2004-2017. Patients with diagnosed hypertension at ART initiation were excluded from the incidence analysis. Log-binomial regression was used to estimate predictors of hypertension at ART initiation, while competing risks regression was used to evaluate the relationship between predictors of incident hypertension, accounting for death as a competing risk. RESULTS: Among 77,696 eligible patients, 22.0% had prevalent hypertension at ART initiation. Of the remaining patients with no hypertension at ART initiation, 8,125 incident hypertension cases were diagnosed over the period of follow-up, corresponding to an incident rate of 5.4 per 100 person-years (95% confidence interval (CI): 5.3-5.6). We found patients ≥40 years of age and patients with a body mass index (BMI) ≥25kg/m2 were at increased risk of both prevalent and incident hypertension. Male patients and those with pre-hypertension at ART initiation had increased hazards of hypertension over the period of follow-up. When assessing the choice of antiretroviral drug in first-line ART, patients initiated on nevirapine were at 27% increased risk of developing hypertension compared to those initiated on efavirenz, while patients who initiated on either zidovudine or stavudine had a 40% increased risk of developing hypertension compared to patients initiated on tenofovir. Patientswith poorer health status at ART initiation (i.e. WHO III/IV stage, low CD4 count, low hemoglobin levels and low BMI) had a decrease risk of prevalent hypertension. We found an inverse relationship in patients with a CD4 count <50 cells/mm3 at ART initiation who had a 25% increased risk of incident hypertension compared to those with a CD4 count ≥350 cells/mm3. CONCLUSION: Over 20% of patients in our cohort had hypertension at ART initiation, and 13% of those with normal blood pressure at ART initiation developed hypertension while on ART. Older patients, males, those on nevirapine, zidovudine or stavudine, and those who are overweight/obese should be targeted for frequent blood pressure monitoring and the identification of other cardiovascular risk factors to encourage lifestyle modifications. Additionally, these groups should be offered pharmaceutical therapy to help prevent myocardial infarction, heart failure, stroke, and kidney disease. Further research is needed to determine the level of access and adherence to pharmaceutical treatment for hypertension in this population. Additionally, an HIV-negative comparison population is needed to assess the association of the HIV virus itself with hypertension.


Assuntos
Antirretrovirais/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Adulto , Antirretrovirais/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , África do Sul/epidemiologia , Adulto Jovem
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