The relative susceptibility of people with HIV (PWH) to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is debated. Numerous studies have been published with apparently ...contradictory findings, but comparisons are difficult because they have been conducted in populations with different characteristics (e.g. age, prevalence comorbidities) and have used different comparison groups (e.g. HIV-negative cohorts, coronavirus disease 2019 (COVID-19) hospitalized patients, general population), and because of challenges to measure the most important confounders. Here, we review the evidence regarding risk and severity of SARS-CoV-2 infection in PWH compared with persons without HIV. Publications originate largely from high-income settings where the majority of the PWH are on antiretroviral therapy (ART). Despite early evidence supporting higher frequency of SARS-CoV-2 testing in PWH on ART, HIV infection is not associated with SARS-CoV-2 infection, once confounding by socioeconomic characteristic is taken into account. Most publications identify increased COVID-19 severity in PWH compared with people without HIV from the general population or compared with COVID-19 hospitalized patients. The only study with an adequate comparison group to reduce confounding, has not identified differences in COVID-19 disease severity by HIV. Publications consistently identify that COVID-19 severity in PWH is not homogeneous and increases with age and baseline comorbidities. As PWH have a higher prevalence of comorbidities than people without HIV, examining their respective contribution to poor health outcomes is not straight forward as comorbidities could mediate the effect of HIV on COVID-19 outcomes.
Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 ...with Spectrum's estimates.
The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts.
In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates.
Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.
Malaria remains a major cause of morbidity and mortality among children under five years old in Equatorial Guinea. However, little is known about the community management of malaria and ...treatment-seeking patterns. We aimed to assess symptoms of children with reported malaria and treatment-seeking behaviour of their caretakers in rural and urban areas in the Bata District.
A cross-sectional study was conducted in the district of Bata and 440 houses were selected from 18 rural villages and 26 urban neighbourhoods. Differences between rural and urban caregivers and children with reported malaria were assessed through the chi-squared test for independence of categorical variables and the t-Student or the non-parametric Mann-Whitney test for normally or not-normally distributed continuous variables, respectively.
Differences between rural and urban households were observed in caregiver treatment-seeking patterns. Fever was the main symptom associated with malaria in both areas. Malaria was treated first at home, particularly in rural areas. The second step was to seek treatment outside the home, mainly at hospital and Health Centre for rural households and at hospital and private clinic for urban ones. Artemether monotherapy was the antimalarial treatment prescribed most often. Households waited for more than 24 hours before seeking treatment outside and delays were longest in rural areas. The total cost of treatment was higher in urban than in rural areas in Bata.
The delays in seeking treatment, the type of malaria therapy received and the cost of treatment are the principal problems found in Bata District. Important steps for reducing malaria morbidity and mortality in this area are to provide sufficient supplies of effective antimalarial drugs and to improve malaria treatment skills in households and in both public and private sectors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IntroductionDespite the availability of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), 21 793 people were newly diagnosed with HIV in Europe in 2019. The Concerted action on ...seroconversion to AIDS and death in Europe study aims to understand current drivers of the HIV epidemic; factors associated with access to, and uptake of prevention methods and ART initiation; and the experiences, needs and outcomes of people with recently acquired HIV.Methods and analysisThis longitudinal observational study is recruiting participants aged ≥16 years with documented laboratory evidence of HIV seroconversion from clinics in Canada and six European countries. We will analyse data from medical records, self-administered questionnaires, semistructured interviews and participatory photography. We will assess temporal trends in transmitted drug resistance and viral subtype and examine outcomes following early ART initiation. We will investigate patient-reported outcomes, well-being, and experiences of, knowledge of, and attitudes to HIV preventions, including PrEP. We will analyse qualitative data thematically and triangulate quantitative and qualitative findings. As patient public involvement is central to this work, we have convened a community advisory board (CAB) comprising people living with HIV.Ethics and disseminationAll respective research ethics committees have approval for data to contribute to international collaborations. Written informed consent is required to take part. A dissemination strategy will be developed in collaboration with CAB and the scientific committee. It will include peer-reviewed publications, conference presentations and accessible summaries of findings on the study’s website, social media and via community organisations.
Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART.
To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ...ART-naive patients in Spain.
During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used.
Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/lamivudine was 1.7%, 1.9% and 0.7%, respectively.
Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.
Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends ...on the frequency with which HIV‐positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first‐line treatment regimen to a new regimen?
We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV‐positive individuals included in the HIV‐CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow‐up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the “no direct effect” assumption. We found little differences on survival and AIDS‐free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV‐RNA threshold of 1000 copies/ml compared with 200 copies/ml. The “no direct effect” assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7‐ to 53‐fold increase in the effective sample size.
The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations.
To describe the ...incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive persons receiving ART.
Cohort study.
HIV clinics in 60 Spanish hospitals between 1 February and 15 April 2020.
77 590 HIV-positive persons receiving ART.
Estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction-confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death. Risk and 95% CIs for COVID-19 diagnosis and hospital admission by use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and others were estimated through Poisson regression models.
Of 77 590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risks for COVID-19 diagnosis and hospitalization were greater in men and persons older than 70 years. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. The corresponding risks for COVID-19 diagnosis were 39.1 (CI, 31.8 to 47.6), 16.9 (CI, 10.5 to 25.9), 28.3 (CI, 21.5 to 36.7), and 29.7 (CI, 22.6 to 38.4), respectively. No patient receiving TDF/FTC was admitted to the ICU or died.
Residual confounding by comorbid conditions cannot be completely excluded.
HIV-positive patients receiving TDF/FTC have a lower risk for COVID-19 and related hospitalization than those receiving other therapies. These findings warrant further investigation in HIV preexposure prophylaxis studies and randomized trials in persons without HIV.
Instituto de Salud Carlos III and National Institutes of Health.
Randomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment ...with direct-acting antiviral (DAA) treatment in individuals with HIV and HCV co-infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non-random samples of individuals with available post-DAA HCV-RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co-infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV-RNA testing.
We included adults with HIV-HCV co-infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV-RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g-formula to impute SVR status for individuals with no SVR assessment.
A total of 4527 individuals who initiated DAA treatment (88% males, median IQR age 56 50, 62 years) were included. Of the total of 642 (14%) individuals had no HCV-RNA test on or after 12 weeks after the end of treatment. The overall observed and g-formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post-DAA and strategies for more systematic routine HCV-RNA testing should be considered.
Our estimates with and without adjustment for missing HCV-RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials.
Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART ...in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL.
We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders.
Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9).
The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART.
National Institutes of Health.
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