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1.
S Afr Med J ; 110(7): 607-609, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32880331

RESUMO

Tuberculosis (TB) is a curable disease, but continues to contribute to large numbers of deaths globally and remains among the leading causes of death in South Africa (SA). Evaluating trends in TB deaths and progress towards the End TB strategy target of zero deaths is particularly important to guide policy and practice in SA. TB deaths are complicated by its relationship with HIV, and SA's initial slow response to HIV compounded this. In considering the reported deaths in SA that identify TB as the underlying cause of death, it is important to be aware of potential limitations and sources of bias. We have examined the relationship between TB and HIV and the recording of underlying and contributing causes of death, and clarified the World Health Organization's methodology for estimating TB deaths.


Assuntos
Tuberculose/mortalidade , Causas de Morte , Atestado de Óbito , Documentação , Infecções por HIV/mortalidade , Humanos , África do Sul/epidemiologia , Estatísticas Vitais , Organização Mundial da Saúde
2.
Lancet HIV ; 7(9): e620-e628, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32890497

RESUMO

BACKGROUND: Antiretroviral therapy (ART) scale-up in sub-Saharan Africa combined with weak routine virological monitoring has driven increasing HIV drug resistance. We investigated ART failure, drug resistance, and early mortality among patients with HIV admitted to hospital in Malawi. METHODS: This observational cohort study was nested within the rapid urine-based screening for tuberculosis to reduce AIDS-related mortality in hospitalised patients in Africa (STAMP) trial, which recruited unselected (ie, irrespective of clinical presentation) adult (aged ≥18 years) patients with HIV-1 at admission to medical wards. Patients were included in our observational cohort study if they were enrolled at the Malawi site (Zomba Central Hospital) and were taking ART for at least 6 months at admission. Patients who met inclusion criteria had frozen plasma samples tested for HIV-1 viral load. Those with HIV-1 RNA of at least 1000 copies per mL had drug resistance testing by ultra-deep sequencing, with drug resistance defined as intermediate or high-level resistance using the Stanford HIVDR program. Mortality risk was calculated 56 days from enrolment. Patients were censored at death, at 56 days, or at last contact if lost to follow-up. The modelling strategy addressed the causal association between HIV multidrug resistance and mortality, excluding factors on the causal pathway (most notably, CD4 cell count, clinical signs of advanced HIV, and poor functional and nutritional status). FINDINGS: Of 1316 patients with HIV enrolled in the STAMP trial at the Malawi site between Oct 26, 2015, and Sept 19, 2017, 786 had taken ART for at least 6 months. 252 (32%) of 786 patients had virological failure (viral load ≥1000 copies per mL). Mean age was 41·5 years (SD 11·4) and 528 (67%) of 786 were women. Of 237 patients with HIV drug resistance results available, 195 (82%) had resistance to lamivudine, 128 (54%) to tenofovir, and 219 (92%) to efavirenz. Resistance to at least two drugs was common (196, 83%), and this was associated with increased mortality (adjusted hazard ratio 1·7, 95% CI 1·2-2·4; p=0·0042). INTERPRETATION: Interventions are urgently needed and should target ART clinic, hospital, and post-hospital care, including differentiated care focusing on patients with advanced HIV, rapid viral load testing, and routine access to drug resistance testing. Prompt diagnosis and switching to alternative ART could reduce early mortality among inpatients with HIV. FUNDING: Joint Global Health Trials Scheme of the Medical Research Council, UK Department for International Development, and Wellcome Trust.


Assuntos
Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Carga Viral , Adulto , Terapia Antirretroviral de Alta Atividade , Duração da Terapia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , HIV-1/genética , Hospitalização , Humanos , Malaui/epidemiologia , Masculino , Mortalidade , RNA Viral , Falha de Tratamento
3.
Lancet ; 396(10248): 402-411, 2020 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-32771107

RESUMO

BACKGROUND: HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. METHODS: We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. FINDINGS: We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. INTERPRETATION: Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade , Adulto , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Fatores de Risco , Tuberculose Resistente a Múltiplos Medicamentos/complicações
4.
Public Health Rep ; 135(1_suppl): 149S-157S, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735185

RESUMO

OBJECTIVE: Federal funds have been spent to reduce the disproportionate effects of HIV/AIDS on racial/ethnic minority groups in the United States. We investigated the association between federal domestic HIV funding and age-adjusted HIV death rates by race/ethnicity in the United States during 1999-2017. METHODS: We analyzed HIV funding data from the Kaiser Family Foundation by federal fiscal year (FFY) and US age-adjusted death rates (AADRs) by race/ethnicity (Hispanic, non-Hispanic white, non-Hispanic black, and Asian/Pacific Islander and American Indian/Alaska Native [API+AI/AN]) from Centers for Disease Control and Prevention WONDER detailed mortality files. We fit joinpoint regression models to estimate the annual percentage change (APC), average APC, and changes in AADRs per billion US dollars in HIV funding, with 95% confidence intervals (CIs). For 19 data points, the number of joinpoints ranged from 0 to 4 on the basis of rules set by the program or by the user. A Monte Carlo permutation test indicated significant (P < .05) changes at joinpoints, and 2-sided t tests indicated significant APCs in AADRs. RESULTS: Domestic HIV funding increased from $10.7 billion in FFY 1999 to $26.3 billion in FFY 2017, but AADRs decreased at different rates for each racial/ethnic group. The average rate of change in AADR per US billion dollars was -9.4% (95% CI, -10.9% to -7.8%) for Hispanic residents, -7.8% (95% CI, -9.0% to -6.6%) for non-Hispanic black residents, -6.7% (95% CI, -9.3% to -4.0%) for non-Hispanic white residents, and -5.2% (95% CI, -7.8% to -2.5%) for non-Hispanic API+AI/AN residents. CONCLUSIONS: Increased domestic HIV funding was associated with faster decreases in age-adjusted HIV death rates for Hispanic and non-Hispanic black residents than for residents in other racial/ethnic groups. Increasing US HIV funding could be associated with decreasing future racial/ethnic disparities in the rate of HIV-related deaths.


Assuntos
Grupos de Populações Continentais/estatística & dados numéricos , Grupos Étnicos/estatística & dados numéricos , Infecções por HIV/etnologia , Infecções por HIV/mortalidade , Prevenção Primária/economia , Síndrome de Imunodeficiência Adquirida/etnologia , Síndrome de Imunodeficiência Adquirida/mortalidade , Humanos , Estados Unidos
6.
Lancet HIV ; 7(9): e629-e640, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32771089

RESUMO

BACKGROUND: The COVID-19 pandemic could lead to disruptions to provision of HIV services for people living with HIV and those at risk of acquiring HIV in sub-Saharan Africa, where UNAIDS estimated that more than two-thirds of the approximately 38 million people living with HIV resided in 2018. We aimed to predict the potential effects of such disruptions on HIV-related deaths and new infections in sub-Saharan Africa. METHODS: In this modelling study, we used five well described models of HIV epidemics (Goals, Optima HIV, HIV Synthesis, an Imperial College London model, and Epidemiological MODeling software [EMOD]) to estimate the effect of various potential disruptions to HIV prevention, testing, and treatment services on HIV-related deaths and new infections in sub-Saharan Africa lasting 6 months over 1 year from April 1, 2020. We considered scenarios in which disruptions affected 20%, 50%, and 100% of the population. FINDINGS: A 6-month interruption of supply of antiretroviral therapy (ART) drugs across 50% of the population of people living with HIV who are on treatment would be expected to lead to a 1·63 times (median across models; range 1·39-1·87) increase in HIV-related deaths over a 1-year period compared with no disruption. In sub-Saharan Africa, this increase amounts to a median excess of HIV deaths, across all model estimates, of 296 000 (range 229 023-420 000) if such a high level of disruption occurred. Interruption of ART would increase mother-to-child transmission of HIV by approximately 1·6 times. Although an interruption in the supply of ART drugs would have the largest impact of any potential disruptions, effects of poorer clinical care due to overstretched health facilities, interruptions of supply of other drugs such as co-trimoxazole, and suspension of HIV testing would all have a substantial effect on population-level mortality (up to a 1·06 times increase in HIV-related deaths over a 1-year period due to disruptions affecting 50% of the population compared with no disruption). Interruption to condom supplies and peer education would make populations more susceptible to increases in HIV incidence, although physical distancing measures could lead to reductions in risky sexual behaviour (up to 1·19 times increase in new HIV infections over a 1-year period if 50% of people are affected). INTERPRETATION: During the COVID-19 pandemic, the primary priority for governments, donors, suppliers, and communities should focus on maintaining uninterrupted supply of ART drugs for people with HIV to avoid additional HIV-related deaths. The provision of other HIV prevention measures is also important to prevent any increase in HIV incidence. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Fármacos Anti-HIV/provisão & distribução , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por HIV/epidemiologia , Modelos Estatísticos , Pandemias , Pneumonia Viral/epidemiologia , África ao Sul do Saara/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Preservativos/provisão & distribução , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Feminino , Saúde Global/tendências , Infecções por HIV/mortalidade , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/crescimento & desenvolvimento , Humanos , Incidência , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Masculino , Pneumonia Viral/mortalidade , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Comportamento Sexual/psicologia , Comportamento Sexual/estatística & dados numéricos , Análise de Sobrevida
7.
J Int AIDS Soc ; 23(8): e25587, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32767707

RESUMO

INTRODUCTION: The COVID-19 pandemic reached the African continent in less than three months from when the first cases were reported from mainland China. As COVID-19 preparedness and response plans were rapidly instituted across sub-Saharan Africa, many governments and donor organizations braced themselves for the unknown impact the COVID-19 pandemic would have in under-resourced settings with high burdens of PLHIV. The potential negative impact of COVID-19 in these countries is uncertain, but is estimated to contribute both directly and indirectly to the morbidity and mortality of PLHIV, requiring countries to leverage existing HIV care systems to propel COVID-19 responses, while safeguarding PLHIV and HIV programme gains. In anticipation of COVID-19-related disruptions, PEPFAR promptly established guidance to rapidly adapt HIV programmes to maintain essential HIV services while protecting recipients of care and staff from COVID-19. This commentary reviews PEPFAR's COVID-19 technical guidance and provides country-specific examples of programme adaptions in sub-Saharan Africa. DISCUSSION: The COVID-19 pandemic may pose significant risks to the continuity of HIV services, especially in countries with high HIV prevalence and weak and over-burdened health systems. Although there is currently limited understanding of how COVID-19 affects PLHIV, it is imperative that public health systems and academic centres monitor the impact of COVID-19 on PLHIV. The general principles of the HIV programme adaptation guidance from PEPFAR prioritize protecting the gains in the HIV response while minimizing in-person home and facility visits and other direct contact when COVID-19 control measures are in effect. PEPFAR-supported clinical, laboratory, supply chain, community and data reporting systems can play an important role in mitigating the impact of COVID-19 in sub-Saharan Africa. CONCLUSIONS: As community transmission of COVID-19 continues and the number of country cases rise, fragile health systems may be strained. Utilizing the adaptive, data-driven programme approaches in facilities and communities established and supported by PEPFAR provides the opportunity to strengthen the COVID-19 response while protecting the immense gains spanning HIV prevention, testing and treatment reached thus far.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Assistência à Saúde , Infecções por HIV/complicações , Pneumonia Viral/complicações , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/mortalidade , África ao Sul do Saara/epidemiologia , China , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Efeitos Psicossociais da Doença , Assistência à Saúde/economia , Assistência à Saúde/normas , Assistência à Saúde/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/mortalidade , Humanos , Cooperação Internacional , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Prevalência
8.
Lancet Glob Health ; 8(9): e1132-e1141, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673577

RESUMO

BACKGROUND: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. METHODS: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. FINDINGS: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. INTERPRETATION: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.


Assuntos
Infecções por Coronavirus/epidemiologia , Países em Desenvolvimento , Infecções por HIV/prevenção & controle , Acesso aos Serviços de Saúde , Malária/prevenção & controle , Pandemias , Pneumonia Viral/epidemiologia , Tuberculose/prevenção & controle , Infecções por HIV/epidemiologia , Infecções por HIV/mortalidade , Humanos , Malária/epidemiologia , Malária/mortalidade , Modelos Teóricos , Tuberculose/epidemiologia , Tuberculose/mortalidade
9.
PLoS Med ; 17(7): e1003116, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32609756

RESUMO

BACKGROUND: Current models of HIV service delivery, with frequent facility visits, have led to facility congestion, patient and healthcare provider dissatisfaction, and suboptimal quality of services and retention in care. The Zambian urban adherence club (AC) is a health service innovation designed to improve on-time drug pickup and retention in HIV care through off-hours facility access and pharmacist-led group drug distribution. Similar models of differentiated service delivery (DSD) have shown promise in South Africa, but observational analyses of these models are prone to bias and confounding. We sought to evaluate the effectiveness and implementation of ACs in Zambia using a more rigorous study design. METHODS AND FINDINGS: Using a matched-pair cluster randomized study design (ClinicalTrials.gov: NCT02776254), 10 clinics were randomized to intervention (5 clinics) or control (5 clinics). At each clinic, between May 19 and October 27, 2016, a systematic random sample was assessed for eligibility (HIV+, age ≥ 14 years, on ART >6 months, not acutely ill, CD4 count not <200 cells/mm3) and willingness to participate in an AC. Clinical and antiretroviral drug pickup data were obtained through the existing electronic medical record. AC meeting attendance data were collected at intervention facilities prospectively through October 28, 2017. The primary outcome was time to first late drug pickup (>7 days late). Intervention effect was estimated using unadjusted Kaplan-Meier survival curves and a Cox proportional hazards model to derive an adjusted hazard ratio (aHR). Medication possession ratio (MPR) and implementation outcomes (adoption, acceptability, appropriateness, feasibility, and fidelity) were additionally evaluated as secondary outcomes. Baseline characteristics were similar between 571 intervention and 489 control participants with respect to median age (42 versus 41 years), sex (62% versus 66% female), median time since ART initiation (4.8 versus 5.0 years), median CD4 count at study enrollment (506 versus 533 cells/mm3), and baseline retention (53% versus 55% with at least 1 late drug pickup in previous 12 months). The rate of late drug pickup was lower in intervention participants compared to control participants (aHR 0.26, 95% CI 0.15-0.45, p < 0.001). Median MPR was 100% in intervention participants compared to 96% in control participants (p < 0.001). Although 18% (683/3,734) of AC group meeting visits were missed, on-time drug pickup (within 7 days) still occurred in 51% (350/683) of these missed visits through alternate means (use of buddy pickup or early return to the facility). Qualitative evaluation suggests that the intervention was acceptable to both patients and providers. While patients embraced the convenience and patient-centeredness of the model, preference for traditional adherence counseling and need for greater human resources influenced intervention appropriateness and feasibility from the provider perspective. The main limitations of this study were the small number of clusters, lack of viral load data, and relatively short follow-up period. CONCLUSIONS: ACs were found to be an effective model of service delivery for reducing late ART drug pickup among HIV-infected adults in Zambia. Drug pickup outside of group meetings was relatively common and underscores the need for DSD models to be flexible and patient-centered if they are to be effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT02776254.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Zâmbia
10.
PLoS One ; 15(7): e0236368, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706836

RESUMO

INTRODUCTION: In the past decade, new diagnostic methods and strategies have appeared, HIV testing efforts and the generalization of antiretroviral therapy may have influenced the number of opportunistic diagnoses and mortality of HIV-infected patients. To test this hypothesis we compiled data on the top opportunistic infections and causes of early death in the HIV cohort of French Guiana. METHODS: HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals from 2010 to 2019 were studied. Annual incidence of different opportunistic infections and annual deaths are compiled. For patients with opportunistic infections we calculated the proportion of early deaths. RESULTS: At the time of analysis, among 2 459 patients, (treated and untreated) 90% had a viral load <400 copies, 91% of the patients in the cohort were on antiretroviral treatment, and 94.2% of patients on treatment for over 6 months had undetectable viral loads. Only 9% of patients had CD4 counts under 200 per mm3. Histoplasmosis clearly remained the most frequent (128 cases) opportunistic infection among HIV-infected persons followed by cerebral toxoplasmosis (63 cases) and esophageal candidiasis (41 cases). Cryptococcal meningitis was ranked 5th most frequent opportunistic infection as was tuberculosis (31 cases). The trend for a sharp decline in early deaths continued (3.9% of patients). CONCLUSIONS: Despite the successes of antiretrovirals, patients presenting with advanced HIV are still common and they are still at risk of dying. Improved diagnosis, and notably systematic screening with appropriate tools are still important areas of potential progress.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Histoplasmose/epidemiologia , Carga Viral/estatística & dados numéricos , Adolescente , Adulto , Candidíase/epidemiologia , Estudos de Coortes , Feminino , Guiana Francesa , HIV-1 , Humanos , Masculino , Meningite Criptocócica/epidemiologia , Pessoa de Meia-Idade , Toxoplasmose Cerebral/epidemiologia , Tuberculose/epidemiologia , Adulto Jovem
11.
Lancet HIV ; 7(7): e463-e471, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32621874

RESUMO

BACKGROUND: Observational data suggest that low vitamin D status is associated with an increased incidence of pulmonary tuberculosis and mortality among people living with HIV. The primary aims of this study were to assess the effect of vitamin D3 supplementation on the risk of mortality and incidence of pulmonary tuberculosis among adults initiating antiretroviral therapy (ART). METHODS: This was a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation among adults living with HIV who initiated ART and had serum 25-hydroxyvitamin D concentrations of less than 30 ng/mL at four large HIV care and treatment centres in Dar es Salaam, Tanzania. Patients were excluded if they were younger than 18 years, pregnant at the time of randomisation, or were enrolled in any other clinical trial. Patients were randomly assigned 1:1 to receive either weekly oral 50 000 IU vitamin D3 supplements (cholecalciferol) for the first month of ART followed by daily 2000 IU vitamin D3 supplements or a matching weekly and daily placebo regimen. The randomisation list was computer-generated by a non-study statistician with sequence blocks of ten that were stratified by study clinic. Complete allocation concealment was ensured and patients, field team, and investigators were masked to group assignment. The trial follow-up duration was 1 year and the primary efficacy outcomes were death and incident pulmonary tuberculosis. An intention-to-treat analysis was followed for all-cause mortality; participants diagnosed with or receiving treatment for pulmonary tuberculosis at randomisation, or suspected to have tuberculosis at randomisation and who later had that diagnosis confirmed, were excluded from analyses of pulmonary tuberculosis incidence. Safety was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT01798680, and is completed. FINDINGS: Between Feb 24, 2014, and Feb 24, 2017, 6250 adults initiating ART had serum 25-hydroxyvitamin D screening, 4000 of whom were enrolled in the trial and followed up for 1 year (follow-up of all participants was completed on March 7, 2018). 2001 patients were randomly assigned to the vitamin D3 supplementation group, and 1999 to the placebo group. 415 deaths were recorded: 211 in the vitamin D3 group and 204 in the placebo group. Among all randomly assigned participants, there was no overall effect of vitamin D3 supplementation on the risk of mortality (hazard ratio [HR] 1·04, 95% CI 0·85-1·25; p=0·73). There was also no difference in the overall incidence of pulmonary tuberculosis between the vitamin D3 (50 events in 1812 patients analysed) and placebo groups (64 events in 1827 patients; HR 0·78, 0·54-1·13; p=0·19). The vitamin D3 regimen did not increase the risk of hypercalcaemia (three events in the vitamin D3 group and two events in the placebo group; relative risk 1·25, 95% CI 0·43-3·66; Fisher's exact p=1·00). 101 hospital admissions were reported in the vitamin D3 group and 94 in the placebo group (incidence rate ratio 1·06, 95% CI 0·80-1·41; p=0·66). INTERPRETATION: Additional research is needed before vitamin D3 supplementation should be considered for implementation in HIV care and treatment programmes for the prevention of pulmonary tuberculosis or mortality. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.


Assuntos
Colecalciferol/farmacologia , Suplementos Nutricionais/análise , Infecções por HIV/tratamento farmacológico , Tuberculose Pulmonar/prevenção & controle , Adulto , Método Duplo-Cego , Feminino , Infecções por HIV/mortalidade , Humanos , Incidência , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Placebos , Tanzânia , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue
13.
Artigo em Inglês | MEDLINE | ID: mdl-32568770

RESUMO

BACKGROUND: SARS-CoV-2 infection continues to cause significant morbidity and mortality worldwide. Preliminary data on SARS-CoV-2 infection suggest that some immunocompromised hosts experience worse outcomes. We performed a retrospective matched cohort study to characterize outcomes in HIV-positive patients with SARS-CoV-2 infection. METHODS: Leveraging data collected from electronic medical records for all patients hospitalized at NYU Langone Health with COVID-19 between March 2, 2020, and April 23, 2020, we matched 21 HIV-positive patients with 42 non-HIV patients using a greedy nearest-neighbor algorithm. Admission characteristics, laboratory test results, and hospital outcomes were recorded and compared between the 2 groups. RESULTS: Although there was a trend toward increased rates of intensive care unit admission, mechanical ventilation, and mortality in HIV-positive patients, these differences were not statistically significant. Rates for these outcomes in our cohort are similar to those previously published for all patients hospitalized with COVID-19. HIV-positive patients had significantly higher admission and peak C-reactive protein values. Other inflammatory markers did not differ significantly between groups, although HIV-positive patients tended to have higher peak values during their clinical course. Three HIV-positive patients had superimposed bacterial pneumonia with positive sputum cultures, and all 3 patients died during hospitalization. There was no difference in frequency of thrombotic events or myocardial infarction between these groups. CONCLUSIONS: This study provides evidence that HIV coinfection does not significantly impact presentation, hospital course, or outcomes of patients infected with SARS-CoV-2, when compared with matched non-HIV patients. A larger study is required to determine whether the trends we observed apply to all HIV-positive patients.


Assuntos
Betacoronavirus , Coinfecção/virologia , Infecções por Coronavirus/complicações , Infecções por HIV/complicações , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Coinfecção/mortalidade , Infecções por Coronavirus/mortalidade , Cuidados Críticos , Feminino , Infecções por HIV/mortalidade , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Respiração Artificial , Estudos Retrospectivos , Resultado do Tratamento
14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(6): 850-855, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32564548

RESUMO

Objective: To understand the survival status and related influencing factors of HIV-infected children aged ≤14 years old, in China. Methods: HIV-infected children were selected from the China's HIV/AIDS Comprehensive Response Information Management System (CRIMS). A retrospective cohort study was conducted to investigate the situation of survival on infected children. Cox proportional hazard regression model was used to screen the factors affecting the survival time. Results: This study involved 8 029 cases of infected children, with a median survival time of 179.75 months. The cumulative survival probabilities at 1 year, 2 years, 5 years, and 10 years after the diagnosis, were 99.13%, 97.95%, 90.11% and 78.63%, respectively. Results from the multivariate Cox proportional hazard regression analysis showed that children who did not receive antiviral therapy were 12.81 times more likely to die than the ones who received the antiretroviral therapy (95%CI: 11.40-14.27). Male HIV-infected children were 1.20 (95%CI: 1.10-1.32) times more likely to die than the female HIV-infected children. The risk of death among HIV positive children at the age of 3 to 5 years was 0.67 (95%CI: 0.60-0.76) times of those children who were diagnosed at the age of 2 years old or younger. The risk of death among children infected with HIV in Northwest was 0.52 (95%CI: 0.29-0.95) times higher than the ones from the Northeast areas of China. The risk of death among children who received antiviral treatment (ART) in the residential areas was 1.96 (95%CI: 1.48-2.61) times than those children who did not. The risk of death from children who did not receive health care services was 2.07 times of those children who did (95%CI: 1.88-2.29). Conclusions: The median survival time of HIV-infected children aged ≤14 years old was 179.75 months, in China. Our findings revealed that initiation of antiviral therapy, female, age, place of receiving ART (out of the residential areas), living in Northwest China, care services and being diagnosed at older age etc. were protective factors influencing the survival time of infected children.


Assuntos
Infecções por HIV/epidemiologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Feminino , Infecções por HIV/mortalidade , Humanos , Lactente , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
15.
N Engl J Med ; 382(25): 2397-2410, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32558469

RESUMO

BACKGROUND: In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. METHODS: We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. RESULTS: A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. CONCLUSIONS: Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hépatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hospedeiro Imunocomprometido , Tuberculose/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Humanos , Masculino , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/mortalidade , Carga Viral
16.
PLoS Med ; 17(5): e1003107, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32401797

RESUMO

BACKGROUND: Men in sub-Saharan Africa have lower engagement and retention in HIV services compared to women, which may result in differential survival. However, the true magnitude of difference in HIV-related mortality between men and women receiving antiretroviral therapy (ART) is incompletely characterized. METHODS AND FINDINGS: We evaluated HIV-positive adults ≥18 years old newly initiating ART in 4 Zambian provinces (Eastern, Lusaka, Southern, and Western). In addition to mortality data obtained from routine electronic medical records, we intensively traced a random sample of patients lost to follow-up (LTFU) and incorporated tracing outcomes through inverse probability weights. Sex-specific mortality rates and rate differences were determined using Poisson regression. Parametric g-computation was used to estimate adjusted mortality rates by sex and age. The study included 49,129 adults newly initiated on ART between August 2013 and July 2015; overall, the median age among patients was 35 years, the median baseline CD4 count was 262 cells/µl, and 37.2% were men. Men comprised a smaller proportion of individuals starting ART (37.2% versus 62.8%), tended to be older (median age 37 versus 33 years), and tended to have lower CD4 counts (median 220 versus 289 cells/µl) at the time of ART initiation compared to women. The overall rate of mortality among men was 10.3 (95% CI 8.2-12.4) deaths/100 person-years (PYs), compared to 5.5 (95% CI 4.3-6.8) deaths/100 PYs among women (difference +4.7 [95% CI 2.3-7.2] deaths/100 PYs; p < 0.001). Compared to women in the same age groups, men's mortality rates were particularly elevated among those <30 years old (+6.7 deaths/100 PYs difference), those attending rural health centers (+9.4 deaths/100 PYs difference), those who had an initial CD4 count < 100 cells/µl (+9.2 deaths/100 PYs difference), and those who were unmarried (+8.0 deaths/100 PYs difference). After adjustment for potential confounders and mediators including CD4 count, a substantially higher mortality rate was predicted among men <30 years old compared to women of the same age, while women ≥50 years old had a mortality rate similar to that of age-matched men, but considerably higher than that predicted among young women (<30 years old). No clinically significant differences were evident with respect to rates of facility transfer or care disengagement between men and women. The main study limitations were the inability to successfully ascertain outcomes in all patients selected for tracing and missing clinical and laboratory data due to the use of medical records. CONCLUSIONS: In this study, we found that among HIV-positive adults newly initiating ART, mortality among men exceeded mortality among women; disparities were most pronounced among young patients. Older women, however, also experienced high mortality. Specific interventions for men and older women at highest mortality risk are needed to improve HIV treatment outcomes.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Registros Eletrônicos de Saúde , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Adulto , Distribuição por Idade , Idoso , Antirretrovirais/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Adulto Jovem , Zâmbia/epidemiologia
17.
Lancet HIV ; 7(5): e332-e339, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32386721

RESUMO

BACKGROUND: Late initiation of HIV antiretroviral therapy (ART) in pregnancy is associated with not achieving viral suppression before giving birth and increased mother-to-child transmission of HIV. We aimed to investigate virological suppression before giving birth with dolutegravir compared with efavirenz, when initiated during the third trimester. METHODS: In this randomised, open-label trial, DolPHIN-2, we recruited pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating ART in third trimester. Participants were randomly assigned (1:1) to dolutegravir-based or efavirenz-based therapy. HIV viral load was measured 7 days and 28 days after antiretroviral initiation, at 36 weeks' gestation, and at the post-partum visit (0-14 days post partum). The primary efficacy outcome was a viral load of less than 50 copies per mL at the first post-partum visit, and the primary safety outcome was the occurrence of drug-related adverse events in mothers and infants until the post-partum visit. Longer-term follow-up of mothers and infants continues. This study is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23, and Aug 15, 2018, we randomly assigned 268 mothers to dolutegravir (135) or efavirenz (133). All mothers and their infants were included in the safety analysis, and 250 mothers (125 in the dolutegravir group, 125 in the efavirenz group) and their infants in efficacy analyses, by intention-to-treat analyses. The median duration of maternal therapy at birth was 55 days (IQR 33-77). 89 (74%) of 120 in the dolutegravir group had viral loads less than 50 copies per mL, compared with 50 (43%) of 117 in the efavirenz group (risk ratio 1·64, 95% CI 1·31-2·06). 30 (22%) of 137 mothers in the dolutegravir group reported serious adverse events compared with 14 (11%) of 131 in the efavirenz group (p=0·013), particularly surrounding pregnancy and puerperium. We found no differences in births less than 37 weeks and less than 34 weeks gestation (16·4% vs 3·3%, across both groups). Three stillbirths in the dolutegravir group and one in the efavirenz group were considered unrelated to treatment. Three infant HIV infections were detected, all in the dolutegravir group, and were considered likely to be in-utero transmissions. INTERPRETATION: Our data support the revision to WHO guidelines recommending the transition to dolutegravir in first-line ART for all adults, regardless of pregnancy or child-bearing potential. FUNDING: Unitaid.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Feminino , Infecções por HIV/mortalidade , Inibidores de Integrase de HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Carga Viral/efeitos dos fármacos
18.
Lancet HIV ; 7(7): e514-e520, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32473102

RESUMO

Patients with advanced HIV disease have a high risk of mortality, mainly from tuberculosis and cryptococcal meningitis. The advanced HIV disease management package recommended by WHO, which includes diagnostics, therapeutics, and patient psychosocial support, is barely implemented in many different countries. Here, we present a framework for the implementation of advanced HIV disease diagnostics. Laboratory and point-of-care-based reflex testing, coupled with provider-initiated requested testing, for cryptococcal antigen and urinary Mycobacterium tuberculosis lipoarabinomannan antigen, should be done for all patients with CD4+ cell counts of 200 cells per µL or less. Implementation of the advanced HIV disease package should be encouraged within primary health-care facilities and task shifting of testing to lay cadres could facilitate access to rapid results. Implementation of differentiated antiretroviral therapy delivery models can allow clinicians enough time to focus on the management of patients with advanced HIV disease. Efficient up-referral and post-discharge systems, including the development of patient-centric advanced HIV disease literacy, are also crucial. Implementation of the advanced HIV disease package is feasible at all health-care levels, and it should be part of the core of the global response towards ending AIDS as a public health threat.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Antirretrovirais/uso terapêutico , Antígenos de Fungos/imunologia , Infecções por HIV/diagnóstico , Implementação de Plano de Saúde , Tuberculose/diagnóstico , África ao Sul do Saara/epidemiologia , Assistência ao Convalescente , Instituições de Assistência Ambulatorial , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Humanos , Alta do Paciente , Testes Imediatos
19.
Infection ; 48(5): 681-686, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32394344

RESUMO

INTRODUCTION: Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. METHODS: Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. RESULTS: Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. CONCLUSIONS: This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Darunavir/uso terapêutico , Infecções por HIV/virologia , HIV/patogenicidade , Pneumonia Viral/virologia , Tenofovir/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Feminino , HIV/efeitos dos fármacos , HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Carga Viral/efeitos dos fármacos
20.
Medicine (Baltimore) ; 99(20): e20146, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443329

RESUMO

BACKGROUND: An increased frequency of toxoplasma encephalitis, caused by Toxoplasma gondii, has been reported in AIDS patients, especially in those with CD4+ T cell counts <100 cells/µL. Several guidelines recommend the combination of pyrimethamine, sulfadiazine, and leucovorin as the preferred regimen for AIDS-associated toxoplasma encephalitis. However, it is not commonly used in China due to limited access to pyrimethamine and sulfadiazine. The synergistic sulfonamides tablet formulation is a combination of trimethoprim (TMP), sulfadiazine and sulfamethoxazole (SMX), and is readily available in China. Considering its constituent components, we hypothesize that this drug may be used as a substitute for sulfadiazine and TMP-SMX. We have therefore designed the present trial, and propose to investigate the efficacy and safety of synergistic sulfonamides combined with clindamycin for the treatment of toxoplasma encephalitis. METHODS/DESIGN: This study will be an open-labeled, multi-center, prospective, randomized, and controlled trial. A total of 200 patients will be randomized into TMP-SMX plus azithromycin group, and synergistic sulfonamides plus clindamycin group at a ratio of 1:1. All participants will be invited to participate in a 48-week follow-up schedule once enrolled. The primary outcomes will be clinical response rate and all-cause mortality at 12 weeks. The secondary outcomes will be clinical response rate and all-cause mortality at 48 weeks, and adverse events at each visit during the follow-up period. DISCUSSION: We hope that the results of this study will be able to provide reliable evidence for the efficacy and safety of synergistic sulfonamides for its use in AIDS patients with toxoplasma encephalitis. TRIAL REGISTRATION: This study was registered as one of 12 clinical trials under the name of a general project at chictr.gov on February 1, 2019, and the registration number of the general project is ChiCTR1900021195. This study is still recruiting now, and the first patient was screened on March 22, 2019.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Toxoplasmose Cerebral/complicações , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome de Imunodeficiência Adquirida/mortalidade , Adolescente , Adulto , Anti-Infecciosos/uso terapêutico , Antiprotozoários/uso terapêutico , China/epidemiologia , Clindamicina/uso terapêutico , Quimioterapia Combinada/métodos , Feminino , Infecções por HIV/mortalidade , Humanos , Leucovorina/uso terapêutico , Masculino , Estudos Prospectivos , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Sulfametoxazol/uso terapêutico , Sulfonamidas/uso terapêutico , T-Linfocitopenia Idiopática CD4-Positiva , Toxoplasma/efeitos dos fármacos , Toxoplasma/parasitologia , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/parasitologia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Complexo Vitamínico B/uso terapêutico
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