Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27.983
Filtrar
1.
Colomb Med (Cali) ; 51(2): e4327, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33012892

RESUMO

Throughout the COVID-19 pandemic, the main risk factors associated with the progression to severe disease or death have been typically advanced age, diabetes mellitus, obesity, high blood pressure, heart disease, and chronic pneumopathy. Because of their immunosuppression status, persons with HIV were also expected to have a higher susceptibility to infection or a poor clinical evolution. So far, this has not been confirmed to happen, giving way to hypotheses about the role of immunosuppression or the use of antiretrovirals, which could explain this paradox. In this article we present the existing data on the epidemiology and characteristics of HIV-COVID-19 co-infection, discuss the available evidence on the possible factors involved in the evolution of individuals affected by both viruses, analyze other determinants that may negatively affect persons with HIV during the pandemic, and present recommendations for the prevention and care of COVID-19 infection in the context of HIV.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por HIV/epidemiologia , Pneumonia Viral/epidemiologia , Coinfecção , Infecções por Coronavirus/prevenção & controle , Progressão da Doença , Infecções por HIV/virologia , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Fatores de Risco
2.
AIDS Res Ther ; 17(1): 59, 2020 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-33012282

RESUMO

INTRODUCTION: During the COVID-19 pandemic, hospitals faced increasing pressure, where people living with HIV risked to either acquire SARS-CoV-2 and to interrupt the HIV continuum of care. METHODS: This is a retrospective, observational study. We compared the numbers of medical visits performed, antiretroviral drugs dispensed and the number of new HIV diagnosis and of hospitalizations in a cohort of people living with HIV (PLWH) followed by the Spedali Civili of Brescia between the bimester of the COVID-19 pandemic peak and the bimester of October-November 2019. Data were retrieved from administrative files and from paper and electronic clinical charts. Categorical variables were described using frequencies and percentages, while continuous variables were described using mean, median, and interquartile range (IQR) values. Means for continuous variables were compared using Student's t-tests and the Mann-Whitney test. Proportions for categorical variables were compared using the χ2 test. RESULTS: As of December 31st, 2019, a total of 3875 PLWH were followed in our clinic. Mean age was 51.4 ± 13 years old, where 28% were females and 18.8% non-Italian. Overall, 98.9% were on ART (n = 3834), 93% were viro-suppressed. A total of 1217 and 1162 patients had their visit scheduled at our out-patient HIV clinic during the two bimesters of 2019 and 2020, respectively. Comparing the two periods, we observed a raise of missed visits from 5 to 8% (p < 0.01), a reduction in the number of new HIV diagnosis from 6.4 in 2019 to 2.5 per month in 2020 (p = 0.01), a drop in ART dispensation and an increase of hospitalized HIV patients due to COVID-19. ART regimens including protease inhibitors (PIs) had a smaller average drop than ART not including PIs (16.6 vs 21.6%, p < 0.05). Whether this may be due to the perception of a possible efficacy of PIs on COVID19 is not known. CONCLUSIONS: Our experience highlights the importance of a resilient healthcare system and the need to implement new strategies in order to guarantee the continuum of HIV care even in the context of emergency.


Assuntos
Infecções por Coronavirus/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Pneumonia Viral/virologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Antirretrovirais/administração & dosagem , Betacoronavirus/isolamento & purificação , Estudos de Coortes , Continuidade da Assistência ao Paciente , Infecções por Coronavirus/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Hospitalização , Humanos , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Saúde Pública , Estudos Retrospectivos , Estatísticas não Paramétricas
3.
Medicine (Baltimore) ; 99(41): e22606, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031315

RESUMO

To determine effects of cryptococcal meningitis (CM) on human immunodeficiency virus (HIV)-1C cerebrospinal fluid (CSF) viral escape, CSF/plasma viral discordance, and drug resistance mutation (DRM) discordance between CSF and plasma compartments, we compared CSF and plasma viral load (VL) and DRMs in individuals with HIV-associated CM in Botswana.This cross-sectional study utilized 45 paired CSF/plasma samples from participants in a CM treatment trial (2014-2016). HIV-1 VL was determined and HIV-1 protease and reverse transcriptase genotyping performed. DRMs were determined using the Stanford HIV database. CSF viral escape was defined as HIV-1 ribonucleic acid ≥0.5 log10 higher in CSF than plasma and VL discordance as CSF VL > plasma VL.HIV-1 VL was successfully measured in 39/45 pairs, with insufficient sample volume in 6; 34/39 (87.2%) participants had detectable HIV-1 in plasma and CSF, median 5.1 (interquartile range: 4.7-5.7) and 4.6 (interquartile range:3.7-4.9) log10 copies/mL, respectively (P≤.001). CSF viral escape was present in 1/34 (2.9%) and VL discordance in 6/34 (17.6%). Discordance was not associated with CD4 count, antiretroviral status, fungal burden, CSF lymphocyte percentage nor mental status. Twenty-six of 45 (57.8%) CSF/plasma pairs were successfully sequenced. HIV-1 DRM discordance was found in 3/26 (11.5%); 1 had I84IT and another had M46MI in CSF only. The third had K101E in plasma and V106 M in CSF.Our findings suggest that HIV-1 escape and DRM discordance may occur at lower rates in participants with advanced HIV-disease and CM compared to those with HIV associated neurocognitive impairment.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/sangue , Infecções por HIV/líquido cefalorraquidiano , HIV-1/genética , Meningite Criptocócica/virologia , Adulto , Estudos Transversais , Feminino , Genes pol , Infecções por HIV/virologia , Humanos , Masculino , Meningite Criptocócica/sangue , Meningite Criptocócica/líquido cefalorraquidiano , Mutação , Estudos Retrospectivos , Carga Viral
5.
Lancet HIV ; 7(10): e666-e676, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33010240

RESUMO

BACKGROUND: ADVANCE compared the efficacy and safety of two antiretroviral first-line combinations (dolutegravir combined with emtricitabine and either tenofovir disoproxil fumarate or tenofovir alafenamide), with a third regimen (efavirenz combined with emtricitabine and tenofovir disoproxil fumarate) previously recommended by WHO. Here, we report the 96-week data for the study. METHODS: This randomised, open-label, non-inferiority phase 3 trial, was done at two research sites in Johannesburg, South Africa, after participant recruitment from 11 public health clinics also in Johannesburg. Eligible participants were aged 12 years or older with HIV-1 infection, who weighed at least 40 kg, had no antiretroviral exposure in the previous 6 months, with a creatinine clearance of more than 60 mL/min (>80 mL per min in individuals aged <19 years), and a plasma HIV-1 RNA concentration of 500 copies per mL or higher. Individuals who were pregnant or had tuberculosis were excluded. Participants were randomly assigned (1:1:1) by study staff using a computerised randomisation system. Randomisation was stratified by age (12 and <19 years and ≥19 years). Participants were randomly assigned to once-daily oral fixed-dose combination tenofovir alafenamide 25 mg and emtricitabine 200 mg, and once-daily oral dolutegravir 50 mg; once-daily oral fixed-dose combination tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg, and once-daily oral dolutegravir 50 mg; or once-daily oral fixed-dose combination of tenofovir disoproxil fumarate 300 mg, emtricitabine 200 mg, and efavirenz 600 mg. The primary efficacy endpoint was the proportion of participants who had a plasma HIV-1 RNA concentration of less than 50 copies per mL at week 48, which has been reported previously. Here, we report the key secondary efficacy endpoint of the proportion of participants who had a plasma HIV-1 RNA concentration of less than 50 copies per mL at the week 96 visit, assessed in all participants who received at least one dose of any study drug, with a prespecified non-inferiority margin of -10%. Safety data, including clinical, dual-energy X-ray absorptiometry and laboratory data, are also reported. This study was registered with ClinicalTrials.gov, NCT03122262. FINDINGS: Between Jan 17, 2017, and May 14, 2018, we screened 1453 individuals, of whom 1053 were enrolled: 351 participants were randomly assigned to the tenofovir alafenamide, emtricitabine, and dolutegravir group, 351 to the tenofovir disoproxil fumarate, emtricitabine, and dolutegravir group, and 351 to the tenofovir disoproxil fumarate, emtricitabine, and efavirenz group. All participants received at least one dose of study medication and were included in the primary analysis. At week 96, 276 (79%) of 351 participants in the tenofovir alafenamide, emtricitabine, and dolutegravir group, 275 (78%) of 351 participants in the tenofovir disoproxil fumarate, emtricitabine, and dolutegravir group, and 258 (74%) of 351 participants in the tenofovir disoproxil fumarate, emtricitabine, and efavirenz group had achieved a plasma HIV-1 RNA concentration of less than 50 copies per mL. Non-inferiority was established in all three comparisons. The proportion of patients with protocol-defined virological failure at week 96 was low in all treatment groups. Participants in the tenofovir alafenamide, emtricitabine, and dolutegravir group had fewer changes in bone density than the two other treatment groups. Mean weight gain was substantial (7·1 kg [SD 7·4] in the tenofovir alafenamide, emtricitabine, and dolutegravir group; 4·3 kg [6·7] in the tenofovir disoproxil fumarate, emtricitabine, and dolutegravir group, and 2·3 kg [7·0] in the tenofovir disoproxil fumarate, emtricitabine, and efavirenz group), and was greater among women than men. Ten (3%) of 351 participants in the tenofovir disoproxil fumarate, emtricitabine, and efavirenz group discontinued due to treatment-related adverse events, of which liver dysfunction (n=4) and rash (n=4) were most common. INTERPRETATION: Medium-term and long-term metabolic and clinical consequences of the considerable increase in bodyweight observed in participants given these antiretroviral regimens and the trajectory of this weight gain over time, especially among women, require further study. FUNDING: USAID, Unitaid, South African Medical Research Council, ViiV Healthcare.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adenina/administração & dosagem , Adenina/análogos & derivados , Adolescente , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/administração & dosagem , Composição Corporal , Peso Corporal , Duração da Terapia , Emtricitabina/administração & dosagem , Feminino , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/administração & dosagem , Resultado do Tratamento , Carga Viral , Adulto Jovem
6.
Lancet HIV ; 7(10): e677-e687, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33010241

RESUMO

BACKGROUND: Updated WHO guidelines recommend a dolutegravir-based regimen as the preferred first-line treatment for HIV infection and low-dose efavirenz (400 mg) as an alternative. We aimed to report the non-inferior efficacy of dolutegravir compared with efavirenz 400 mg at week 96. METHODS: We did a multicentre, randomised, open label, phase 3 trial in in three hospitals in Yaoundé, Cameroon, in HIV-1 infected antiretroviral-naive adults with an HIV RNA viral load of greater than 1000 copies per mL to compare dolutegravir 50 mg with efavirenz 400 mg (reference treatment), both combined with lamivudine and tenofovir disoproxil fumarate. The primary endpoint was the proportion with a viral load of less than 50 copies per mL at week 48 (10% non-inferiority margin). The study is registered with ClinicalTrials.gov, NCT02777229 and is ongoing. FINDINGS: Between July, 2016, and August, 2019, of 820 patients assessed, 613 were randomly assigned to receive at least one dose of study medication, with 310 in the dolutegravir group and 303 in the efavirenz 400 mg group. At week 96 in the intention-to-treat analysis, 229 (74%) of 310 patients receiving dolutegravir and 219 (72%) of 303 patients receiving efavirenz, achieved plasma HIV-1 RNA less than 50 copies per mL (difference 1·6%, 95% CI -5·4 to 8·6; p=0.66). Viral load suppression was reached significantly more rapidly in the dolutegravir group (p<0·001). Virological failure (>1000 copies per mL) was observed in 27 patients (eight in the dolutegravir group, among which, three women switched to efavirenz 600 mg because of the dolutegravir teratogeneicity signal, and 19 in the efavirenz 400 mg group). No acquired resistance mutations to dolutegravir were observed against 17 mutations to efavirenz with or without mutations to lamivudine and tenofovir disoproxil fumarate among the 19 efavirenz 400 mg participants with virological failure. Weight gain was greater in the dolutegravir group (median weight gain, 5·0 kg in the dolutegravir group and 3·0 kg in the efavirenz 400 mg group, p<0·001, and incidence of obesity, 22% in the dolutegravir group and 16% in the efavirenz 400 mg group, p=0·043). The incidence of new WHO HIV-related stage 3 and 4 events was similar in each group (12 [4%] in each group). The two groups had similar rates of serious adverse events (28 [9%] of 310 in the dolutegravir group and 21 [7%] of 303 in the efavirenz 400 mg group). 18 deaths were observed during the 96-week follow-up (eight in the dolutegravir group and ten in the efavirenz 400 mg group). INTERPRETATION: The non-inferior efficacy of the dolutegravir-based regimen and non-emergence of dolutegravir resistance at 96 weeks supports its use as a first-line regimen for antiretroviral-naive adults with HIV-1 infection. Viral load suppression was reached more quickly in the dolutegravir group and weight gain was significantly higher. FUNDING: UNITAID and the French National Agency for AIDS Research.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Benzoxazinas/administração & dosagem , Contagem de Linfócito CD4 , Duração da Terapia , Feminino , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Carga Viral , Adulto Jovem
7.
BMC Infect Dis ; 20(1): 727, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023498

RESUMO

BACKGROUND: Viral load (VL) testing is the gold-standard approach for monitoring human immunodeficiency virus (HIV) treatment success and virologic failure, but uptake is suboptimal in resource-limited and rural settings. We conducted a cross-sectional study of risk factors for non-uptake of VL testing in rural Uganda. METHODS: We conducted a cross-sectional analysis of uptake of VL testing among randomly selected people with HIV (PWH) receiving anti-retroviral treatment (ART) for at least 6 months at all eight primary health centers in Gomba district, rural Uganda. Socio-demographic and clinical data were extracted from medical records for the period January to December 2017. VL testing was routinely performed 6 months after ART initiation and 12 months thereafter for PWH stable on ART. We used descriptive statistics and multivariable logistic regression to evaluate factors associated with non-uptake of VL testing (the primary outcome). RESULTS: Of 414 PWH, 60% were female, and the median age was 40 years (interquartile range [IQR] 31-48). Most (62.3%) had been on ART > 2 years, and the median duration of treatment was 34 months (IQR 14-55). Thirty three percent did not receive VL testing: 36% of women and 30% of men. Shorter duration of ART (≤2 years) (adjusted odds ratio [AOR] 2.38; 95% CI:1.37-4.12; p = 0.002), younger age 16-30 years (AOR 2.74; 95% CI:1.44-5.24; p = 0.002) and 31-45 years (AOR 1.92; 95% CI 1.12-3.27; p = 0.017), and receipt of ART at Health Center IV (AOR 2.85; 95% CI: 1.78-4.56; p < 0.001) were significantly associated with non-uptake of VL testing. CONCLUSIONS: One-in-three PWH on ART missed VL testing in rural Uganda. Strategies to improve coverage of VL testing, such as VL focal persons to flag missed tests, patient education and demand creation for VL testing are needed, particularly for recent ART initiates and younger persons on treatment, in order to attain the third Joint United Nations Program on HIV/AIDS (UNAIDS) 95-95-95 target - virologic suppression for 95% of PWH on ART.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/imunologia , População Rural , Carga Viral/efeitos dos fármacos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/virologia , Humanos , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Testes Sorológicos , Resposta Viral Sustentada , Uganda/epidemiologia , Adulto Jovem
8.
BMC Infect Dis ; 20(1): 742, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036558

RESUMO

BACKGROUND: The surge of methamphetamine use has been a complicating factor compounding the steeply increasing number of drug overdose deaths in the U.S. Infection from blood-borne viruses including hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV, related to methamphetamine use continue to grow. This study aims to examine the risk factors associated with HBV, HCV and HIV among people who used methamphetamine. METHODS: People who ever used methamphetamine were identified from five National Health and Nutrition Examination Survey (NHANES) cohorts, 2007 to 2016. The outcome was either positive or negative for blood-borne viruses as identified from laboratory tests. Weighted statistics for the combined ten years of data were calculated by multiplying the weighted variable for laboratory measurements by 0.2. We examined the association of sexual activities (sexual partners, sexual identity), drug use behaviors (poly-drug use, injection drug use, frequency of drug use, age started using methamphetamine), demographics, and socio-economic status with blood-borne viruses using bivariate and multivariable logistic regression models. RESULTS: There were 1132 participants representing approximately 11,996,319 persons who ever used methamphetamine in the U.S. Blood-borne viruses' positive rate was 13.0 per 100,000. Multivariable logistic regression analyses showed significant associations of blood-borne infections with age 40-49 years (vs. age 20-29 years, adjusted odds ratio 4.77, 95% CI 1.11-20.55), age 50-59 years (vs. age 20-29 years, 10.25, 2.40-43.82), living within poverty index 1-1.9 (vs. poverty index > = 2, 2.55; 1.19-5.49), living below the poverty threshold (vs. poverty index > = 2, 2.55; 1.11-5.86), having lower than high school education (vs. equal or higher than high school education, 3.13; 1.51-6.46), sexual identity as other than heterosexual (vs. heterosexual, 5.60; 1.72-18.28), using methamphetamine and heroin and cocaine (vs. using methamphetamine alone, 4.24; 1.06-16.92), injection drug use (vs. no injection drug use, 3.15; 1.61-6.16), and started using methamphetamine at age above 25 (vs. started using methamphetamine at age between 10 and 17, 2.09; 1.01-4.35). CONCLUSIONS: Among people who use methamphetamine, those who use polysubstance, or who inject substances, are in urgent need for vaccination and interventions to avoid further harm from blood borne infections.


Assuntos
Infecções por HIV/epidemiologia , HIV-1/imunologia , HIV-2/imunologia , Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Metanfetamina , Abuso de Substâncias por Via Intravenosa , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por HIV/virologia , Hepatite B/virologia , Hepatite C/virologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Razão de Chances , Fatores de Risco , Assunção de Riscos , Testes Sorológicos , Comportamento Sexual , Parceiros Sexuais , Adulto Jovem
10.
PLoS Comput Biol ; 16(9): e1008122, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32881984

RESUMO

Spread of HIV typically involves uneven transmission patterns where some individuals spread to a large number of individuals while others to only a few or none. Such transmission heterogeneity can impact how fast and how much an epidemic spreads. Further, more efficient interventions may be achieved by taking such transmission heterogeneity into account. To address these issues, we developed two phylogenetic methods based on virus sequence data: 1) to generally detect if significant transmission heterogeneity is present, and 2) to pinpoint where in a phylogeny high-level spread is occurring. We derive inference procedures to estimate model parameters, including the amount of transmission heterogeneity, in a sampled epidemic. We show that it is possible to detect transmission heterogeneity under a wide range of simulated situations, including incomplete sampling, varying levels of heterogeneity, and including within-host genetic diversity. When evaluating real HIV-1 data from different epidemic scenarios, we found a lower level of transmission heterogeneity in slowly spreading situations and a higher level of heterogeneity in data that included a rapid outbreak, while R0 and Sackin's index (overall tree shape statistic) were similar in the two scenarios, suggesting that our new method is able to detect transmission heterogeneity in real data. We then show by simulations that targeted prevention, where we pinpoint high-level spread using a coalescence measurement, is efficient when sequence data are collected in an ongoing surveillance system. Such phylogeny-guided prevention is efficient under both single-step contact tracing as well as iterative contact tracing as compared to random intervention.


Assuntos
Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , HIV-1/classificação , HIV-1/genética , Algoritmos , Biologia Computacional , Simulação por Computador , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Filogenia
11.
PLoS One ; 15(8): e0238052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866163

RESUMO

The integrase inhibitor dolutegravir was included in initial antiretroviral therapy in Brazil in January 2017. Studies have demonstrated that the efficacy and safety of antiretrovirals have improved with the introduction of new classes of antiretrovirals, such as integrase inhibitors. This study aimed to estimate the frequency of individuals with a virologic response by week 24 of antiretroviral treatment and to describe the adverse events of the regimen containing dolutegravir. This was a cohort of people living with HIV followed up at a referral hospital. Patients were included who had initiated their first treatment between January and August 2017. Data were obtained from medical records, the Drug Logistics Management System and from the Laboratory Tests Control System. Two hundred and twenty-two patients were included for the tolerability analysis and one hundred and thirty-seven for the virologic response analysis. The mean age was 34 years, the median time between diagnosis and initiating treatment was 1.9 months and the median time on antiretroviral therapy was 13.2 months. The frequency of adverse events was 10% (95% CI: 7% to 15.2%), of these, amongst the most frequent events, 91% presented gastrointestinal effects, and 47.8% neuropsychiatric. By week 24 the estimated incidence of virologic response was 89.1% (95% CI: 83% to 93.5%), with an increase during the first 6 months in the number of T-CD4 lymphocytes of 50.7 cells/mm 3 (95% CI: 42 to 59.3). Initial antiretroviral regimens containing dolutegravir were well tolerated and effective in viral suppression during the first 24 weeks after initiating treatment. The occurrence of adverse events was low, either mild or moderate.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Segurança , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Feminino , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Virologia
12.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(8): 1335-1340, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32867446

RESUMO

Objective: To understand the characteristics of HIV-1 genotypes and drug resistance among men who have sex with men in Kunming in 2018. Methods: A total of 193 plasma samples were collected from the newly reported HIV-1 infected MSM in Kunming from January to December 2018. Viral RNA was extracted, and the gag, pol, env gene segments were amplified by nested PCR. HIV-1 genotypes and drug resistance were also analyzed. Subsequently, the evolutionary characteristics of CRF55_01B and CRF68_01B among MSM in Kunming were analyzed by Bayesian Markov Chain Monte Carlo method. Results: Multiple HIV-1 genotypes were identified among these 193 samples, including CRF07_BC (39.4%, 76/193), CRF01_AE (34.2%, 66/193), unique recombinant forms (URFs) (20.2%, 39/193), CRF08_BC (3.1%, 6/193), CRF55_01B (1.6%, 3/193), subtype B (1.0%, 2/193) and CRF68_01B (0.5%, 1/193). Results from the Bayesian evolutionary analysis showed that CRF55_01B started to spread locally after being imported from other provinces, while CRF68_01B was likely to have been brought in from the eastern provinces of China. Prevalence of HIV-1 drug resistant strains was 2.6%(5/190) before antiviral treatment, with mutation rates resistant to non-nucleoside reverse transcriptase inhibitors being the highest (2.1%, 4/190) among MSM in Kunming, 2018. Conclusion: The diversity of HIV-1 was increasing among MSM in Kunming. Although the resistance rate on pretreatment drug was relatively low, the emergence of multiple resistant strains to first-line antiviral drugs posed a challenge to antiretroviral therapy, in Kunming.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1/genética , Homossexualidade Masculina , Teorema de Bayes , China/epidemiologia , Genótipo , Infecções por HIV/epidemiologia , Humanos , Masculino
13.
BMC Public Health ; 20(1): 1375, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907565

RESUMO

BACKGROUND: Measuring progress towards the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 treatment targets is key to assessing progress towards turning the HIV epidemic tide. In 2017, the UNAIDS model estimated that 75% of people living with HIV (PLHIV) globally knew their HIV positive status, 79% of those who knew their status were on antiretroviral therapy (ART), and 81% of those who knew their HIV status and were on ART had a suppressed viral load. The fifth South African national HIV sero-behavioural survey collected nationally representative data that enabled the empirical estimation of these 90-90-90 targets for the country stratified by a variety of key factors. METHODS: To evaluate progress towards achievement of the 90-90-90 targets for South Africa, data obtained from a national, representative, cross-sectional population-based multi-stage stratified cluster random survey conducted in 2017 were analysed. The Fifth South African National HIV Prevalence, Incidence, Behaviour and Communication Survey (SABSSM V), collected behavioural and biomarker data from individuals residing in households from 1000 randomly selected Small Area Layers (SALs), across all nine provinces of the country. Structured questionnaires were used to collect socio-demographic data, knowledge and perceptions about HIV, and related risk behaviours. Blood samples were collected to test for HIV infection, antiretroviral use, and viral suppression (defined as < 1000 copies/ml). Weighted proportions of study participants aged 15 years and older who tested HIV positive were computed for those who reported awareness of their status (1st 90), and among these, those who were currently on ART (2nd 90) and of these, those who were virally suppressed (3rd 90). RESULTS: Among persons 15 years and older who were HIV positive, 84.8% were aware of their HIV positive status, of whom 70.7% were currently on ART, with 87.4% of these estimated to have suppressed viral load at the time of the survey. These estimates varied by sex, age, and geo-location type. Relatively higher percentages across all three indicators for women compared to men were observed: 88.7% versus 78.2% for those aware of their status, 72.3% versus 67.7% for on ART, and 89.8% versus 82.3% for viral suppression. Knowing one's positive HIV status increased with age: 74.0, 85.8, and 88.1% for age groups 15-24 years old, 25-49 years old and 50-64 years old, although for those 65 years and older, 78.7% knew their HIV positive status. A similar pattern was observed for the 2nd 90, among those who knew their HIV positive status, 51.7% of 15 to 24 year olds, 70.5% of those aged 25-49 years old, 82.9% of those aged 50-64 years old and 82.4% of those aged 65 years or older were currently on ART. Viral suppression for the above mentioned aged groups, among those who were on ART was 85.2, 87.2, 89.5, and 84.6% respectively. The 90-90-90 indicators for urban areas were 87.7, 66.5, and 87.2%, for rural settings was 85.8, 79.8, and 88.4%, while in commercial farming communities it was 56.2, 67.6 and 81.4%. CONCLUSIONS: South Africa appears to be on track to achieve the first 90 indicator by 2020. However, it is behind on the second 90 indicator with ART coverage that was ~ 20-percentage points below the target among people who knew their HIV status, this indicates deficiencies around linkage to and retention on ART. Overall viral suppression among those on ART is approaching the target at 87.4%, but this must be interpreted in the context of low reported ART coverage as well as with variation by age and sex. Targeted diagnosis, awareness, and treatment programs for men, young people aged 15-24 years old, people who reside in farming communities, and in specific provinces are needed. More nuanced 90-90-90 estimates within provinces, specifically looking at more granular sub-national level (e.g. districts), are needed to identify gaps in specific regions and to inform provincial interventions.


Assuntos
Antirretrovirais/uso terapêutico , Conscientização , Epidemias , Objetivos , Infecções por HIV/prevenção & controle , Carga Viral , Logro , Síndrome de Imunodeficiência Adquirida/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural , África do Sul/epidemiologia , Inquéritos e Questionários , Nações Unidas , Adulto Jovem
15.
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
16.
PLoS Pathog ; 16(9): e1008764, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32881968

RESUMO

To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust and comparable between arms, while antibody-dependent neutrophil and monocyte phagocytotic responses were greatly enhanced by ALFA. Per-exposure vaccine efficacy against heterologous tier 2 SHIV mucosal challenge was 90% in ALFA-adjuvanted males (P = 0.002), while alum conferred no protection. Half of the ALFA-adjuvanted males remained uninfected after the full challenge series, which spanned seven months after the last vaccination. Antibody-dependent monocyte and neutrophil phagocytic responses both strongly correlated with protection. Significant sex differences in infection risk were observed, with much lower infection rates in females than males. In humans, MPLA-liposome-alum adjuvanted gp120 also increased HIV-1-specific phagocytic responses relative to alum. Thus, next-generation liposome-based adjuvants can drive vaccine elicited antibody effector activity towards potent phagocytic responses in both macaques and humans and these responses correlate with protection. Future protein vaccination strategies aiming to improve functional humoral responses may benefit from such adjuvants.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/prevenção & controle , Vacinas contra a SAIDS/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Adolescente , Adulto , Animais , Anticorpos Neutralizantes/imunologia , Método Duplo-Cego , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/imunologia , Humanos , Macaca mulatta , Masculino , Pessoa de Meia-Idade , Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/imunologia , Adulto Jovem
17.
PLoS Pathog ; 16(9): e1008744, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898182

RESUMO

In HIV-hepatitis B virus (HBV) co-infection, adverse liver outcomes including liver fibrosis occur at higher frequency than in HBV-mono-infection, even following antiretroviral therapy (ART) that suppresses both HIV and HBV replication. To determine whether liver disease was associated with intrahepatic or circulating markers of inflammation or burden of HIV or HBV, liver biopsies and blood were collected from HIV-HBV co-infected individuals (n = 39) living in Bangkok, Thailand and naïve to ART. Transient elastography (TE) was performed. Intrahepatic and circulating markers of inflammation and microbial translocation were quantified by ELISA and bead arrays and HIV and HBV infection quantified by PCR. Liver fibrosis (measured by both transient elastography and liver biopsy) was statistically significantly associated with intrahepatic mRNA for CXCL10 and CXCR3 using linear and logistic regression analyses adjusted for CD4 T-cell count. There was no evidence of a relationship between liver fibrosis and circulating HBV DNA, qHBsAg, plasma HIV RNA or circulating cell-associated HIV RNA or DNA. Using immunohistochemistry of liver biopsies from this cohort, intrahepatic CXCL10 was detected in hepatocytes associated with inflammatory liver infiltrates in the portal tracts. In an in vitro model, we infected an HBV-infected hepatocyte cell line with HIV, followed by interferon-γ stimulation. HBV-infected cells lines produced significantly more CXCL10 than uninfected cells lines and this significantly increased in the presence of an increasing multiplicity of HIV infection. Conclusion: Enhanced production of CXCL10 following co-infection of hepatocytes with both HIV and HBV may contribute to accelerated liver disease in the setting of HIV-HBV co-infection.


Assuntos
Quimiocina CXCL10/metabolismo , Coinfecção/complicações , Infecções por HIV/complicações , HIV/isolamento & purificação , Vírus da Hepatite B/isolamento & purificação , Hepatite B/complicações , Cirrose Hepática/epidemiologia , Adulto , Austrália/epidemiologia , Estudos de Coortes , Coinfecção/virologia , Feminino , Infecções por HIV/virologia , Hepatite B/virologia , Humanos , Incidência , Cirrose Hepática/metabolismo , Cirrose Hepática/virologia , Masculino , Países Baixos/epidemiologia , Prognóstico , Tailândia/epidemiologia
19.
PLoS Pathog ; 16(9): e1008813, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32925973

RESUMO

HIV Nef counteracts cellular host restriction factors SERINC3 and SERINC5, but our understanding of how naturally occurring global Nef sequence diversity impacts these activities is limited. Here, we quantify SERINC3 and SERINC5 internalization function for 339 Nef clones, representing the major pandemic HIV-1 group M subtypes A, B, C and D. We describe distinct subtype-associated hierarchies for Nef-mediated internalization of SERINC5, for which subtype B clones display the highest activities on average, and of SERINC3, for which subtype B clones display the lowest activities on average. We further identify Nef polymorphisms that modulate its ability to counteract SERINC proteins, including substitutions in the N-terminal domain that selectively impair SERINC3 internalization. Our findings demonstrate that the SERINC antagonism activities of HIV Nef differ markedly among major viral subtypes and between individual isolates within a subtype, suggesting that variation in these functions may contribute to global differences in viral pathogenesis.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Glicoproteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/antagonistas & inibidores , Polimorfismo Genético , Replicação Viral , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo , Infecções por HIV/genética , Infecções por HIV/metabolismo , Soropositividade para HIV , Interações Hospedeiro-Patógeno , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Células Tumorais Cultivadas , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética
20.
PLoS One ; 15(9): e0236320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941433

RESUMO

HIV-infected older individuals may have a diminished immune response because of exhaustion/immune aging of T-cells. Therefore, we have investigated HIV-specific CD4 and CD8 T-cell responses in 100 HIV-infected patients (HIV+) who have aged on long-term antiretroviral therapy (ART) and achieved controlled viremia (mostly undetectable viral load; 92 patients with <20 to <40 HIV RNA copies/mL and 8 <60 to <100) and improved CD4 T-cell counts. We show that the median frequencies of HIV-specific CD4+ and CD8+ IFN-γ T-cells were higher in HIV+ than uninfected individuals (HIV-), including increasing levels of IFN-γproduced by CD4+ T-cells and decreasing levels by CD8+ T-cells with increasing CD4 T-cell counts in HIV+. No correlation was found between T-cell responses and varying levels of undetectable viremia. HIV-specific TNF-α made by CD8+ T-cells was higher in HIV+ than HIV-, including decreasing levels with increasing CD4 T-cell counts in HIV+. Furthermore, the CD8+ T-cell mediators, CD107a and Granzyme-B, were higher in HIV+ than HIV-, and decreased with increasing CD4 T-cell counts in HIV+. Remarkably, HIV-specific CD8 T-cells produced decreasing levels of IFN-γwith increasing age of HIV+, including decreased levels of CD107a and Granzyme-B in older HIV+. However, HIV-specific CD8+ T-cells produced increasing levels of TNF-α with increasing age of the HIV+, suggesting continued inflammation. In conclusion, HIV+ with controlled viremia on long-term ART and with higher CD4 T-cell counts showed reduced HIV-specific CD8 T-cell responses as compared to those with lower CD4 T-cell counts, and older HIV+ exhibited decreasing levels of CD8 T-cell responses with increasing age.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/sangue , Linfócitos T/imunologia , Viremia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirretrovirais/administração & dosagem , Relação CD4-CD8 , Feminino , Granzimas/genética , Granzimas/metabolismo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Proteína 1 de Membrana Associada ao Lisossomo/genética , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Viremia/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA