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Background The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic.Methods To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0•03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1•0). FindingsIn 2019, there were 36•8 million (95% uncertainty interval [UI] 35•1-38•9) people living with HIV worldwide. There were 0•84 males (95% UI 0•78-0•91) per female living with HIV in 2019, 0•99 male infections (0•91-1•10) for every female infection, and 1•02 male deaths (0•95-1•10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28•52% decrease in incident cases, 95% UI 19•58-35•43, and a 39•66% decrease in deaths, 36•49-42•36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0•05 (95% UI 0•05-0•06) and the global incidence-to-mortality ratio was 1•94 (1•76-2•12). No regions met suggested thresholds for progress.Interpretation Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics.

Background Tuberculosis is a major contributor to the global burden of disease, causing more than a million deaths annually. Given an emphasis on equity in access to diagnosis and treatment of tuberculosis in global health targets, evaluations of differences in tuberculosis burden by sex are crucial. We aimed to assess the levels and trends of the global burden of tuberculosis, with an emphasis on investigating differences in sex by HIV status for 204 countries and territories from 1990 to 2019. MethodsWe used a Bayesian hierarchical Cause of Death Ensemble model (CODEm) platform to analyse 21 505 siteyears of vital registration data, 705 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, and 680 site-years of mortality surveillance data to estimate mortality due to tuberculosis among HIV-negative individuals. We used a population attributable fraction approach to estimate mortality related to HIV and tuberculosis coinfection. A compartmental meta-regression tool (DisMod-MR 2.1) was then used to synthesise all available data sources, including prevalence surveys, annual case notifications, population-based tuberculin surveys, and tuberculosis cause-specific mortality, to produce estimates of incidence, prevalence, and mortality that were internally consistent. We further estimated the fraction of tuberculosis mortality that is attributable to independent effects of risk factors, including smoking, alcohol use, and diabetes, for HIV-negative individuals. For individuals with HIV and tuberculosis coinfection, we assessed mortality attributable to HIV risk factors including unsafe sex, intimate partner violence (only estimated among females), and injection drug use. We present 95% uncertainty intervals for all estimates.Findings Globally, in 2019, among HIV-negative individuals, there were 1•18 million (95% uncertainty interval 1•08-1•29) deaths due to tuberculosis and 8•50 million (7•45-9•73) incident cases of tuberculosis. Among HIV-positive individuals, there were 217 000 (153 000-279 000) deaths due to tuberculosis and 1•15 million (1•01-1•32) incident cases in 2019. More deaths and incident cases occurred in males than in females among HIV-negative individuals globally in 2019, with 342 000 (234 000-425 000) more deaths and 1•01 million (0•82-1•23) more incident cases in males than in females. Among HIV-positive individuals, 6250 (1820-11 400) more deaths and 81 100 (63 300-100 000) more incident cases occurred among females than among males in 2019. Age-standardised mortality rates among HIV-negative males were more than two times greater in 105 countries and age-standardised incidence rates were more than 1•5 times greater in 74 countries than among HIV-negative females in 2019. The fraction of global tuberculosis deaths among HIV-negative individuals attributable to alcohol use, smoking, and diabetes was 4•27 (3•69-5•02), 6•17 (5•48-7•02), and 1•17 (1•07-1•28) times higher, respectively, among males than among females in 2019. Among individuals with HIV and tuberculosi...

Coronavirus disease 2019 (COVID‐19) caused by SARS‐CoV‐2 has been associated with a high risk of adverse outcomes in solid organ transplant (SOT) recipients in the pre‐vaccination era. In this retrospective cohort study, we examined the incidence and severity of COVID‐19 in kidney and liver transplant recipients in Denmark in the post‐vaccination era, from December 27, 2020, to December 27, 2021. We included 1428 SOT recipients with 143 cases of first‐positive SARS‐CoV‐2 PCR test. The cumulative incidence of first‐positive SARS‐CoV‐2 PCR test 1 year after initiation of vaccination was 10.4% (95% CI: 8.8–12.0), and the incidence was higher in kidney than in liver transplant recipients (11.6% [95% CI: 9.4–13.8] vs. 7.4% [95% CI: 5.1–9.8], p = .009). After the first‐positive SARS‐CoV‐2 PCR test, the hospitalization rate was 31.5% (95% CI: 23.9–39.1), and 30‐day all‐cause mortality was 3.7% (95% CI: 0.5–6.8). Hospitalization was lower in vaccinated than in unvaccinated SOT recipients (26.4% [95% CI: 18.1–34.6] vs. 48.5% [95% CI: 31.4–65.5], p = .011), as was mortality (1.8% [95% CI: 0.0–4.3] vs. 9.1% [95% CI: 0.0–18.9], p = .047). In conclusion, SOT recipients remain at high risk of adverse outcomes after SARS‐CoV‐2 infections, with a lower risk observed in vaccinated than in unvaccinated SOT recipients.

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Background Mumps, measles, rubella, and varicella zoster (MMRV) viruses may cause severe infections in seronegative adult solid organ transplant (SOT) recipients, but can be prevented by vaccination. We aimed to determine MMRV serostatus in adult SOT recipients before and 1 year after transplantation as well as evidence of MMRV infections in a large, prospective cohort of SOT recipients. Methods This was a prospective study of 1182 adult SOT recipients included in the Management of Posttransplant Infections in Collaborating Hospitals (MATCH) cohort from 2011 to 2017 with a 1-year follow-up. Systematic monitoring of MMRV serology was performed prior to transplantation and 1 year posttransplantation. Polymerase chain reaction (PCR) was used to confirm viral replication in SOT recipients presenting with clinical evidence of infection. Results Among 1182 adult SOT recipients, 28 (2.4%), 77 (6.5%), 65 (5.5%), and 22 (1.9%) were seronegative for measles, mumps, rubella, and varicella zoster virus (VZV), respectively, and 165 (14%) were seronegative for at least 1 of the MMRV viruses. One year posttransplantation, 29 of 823 (3.5%) of seropositive SOT recipients had seroreverted, and 63 of 111 (57%) of seronegative SOT recipients seroconverted for at least 1 MMRV virus. No evidence of measles, mumps, or rubella infection was found, but 8 (0.7%) SOT recipients developed symptoms and had a positive VZV PCR. Conclusions A large proportion of SOT recipients were seronegative for at least 1 of the MMRV viruses. MMRV infections in SOT recipients may disseminate and become fatal, and although only a few cases of VZV infection were detected, results from this study suggest increase attention toward vaccination of patients waiting for SOT.

Background: Defining the optimal dosage of the immunosuppressive or duration of anti-infective agents is a challenge in solid organ transplant (SOT) recipients. We aimed to systematically review the literature regarding the use of T cell mediated immune functional assays (IFAs) for adjustment of the immunosuppressive or anti-infective agents in SOT recipients. Methods: We systematically searched PubMed, Scopus, EMBASE, Web of Science (WOS), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to find human interventional studies or study protocols that used either in-house or commercially available IFAs for adjustment of the immunosuppressive or anti-infective agents in SOT recipients. Results: We included six clinical trials and six study protocols. Four out of the six clinical trials used interferon-γ release assays for cytomegalovirus (IGRA-CMV), and five out of the six registered study protocols planned to use IGRA-CMV for adjustment of anti-CMV antiviral (Valganciclovir) prophylaxis or preemptive therapy in SOT recipients. Primary or secondary anti-CMV prophylaxes were discontinued in SOT recipients who had positive IGRA-CMV results without an increase in the rate of CMV infection or reactivation. Among other IFAs, one clinical trial used interferon-γ release assays for tuberculosis (IGRA-TB), and one study used ImmuKnow for adjustment of the duration and dosage of isoniazid and tacrolimus, respectively. Conclusion: Our systematic review supports a promising role for the IGRA-CMVs for adjustment of the duration of anti-CMV antiviral prophylaxis in SOT recipients. There are limited data to support the use of IFAs other than IGRA-CMVs for adjustment of Rezahosseini et al. Immune Functional Assays in SOT-Recipients immunosuppressive or anti-infective agents. Further multicenter randomized clinical trials using IFAs other than IGRA-CMVs may help in personalized immunosuppressive or prophylactic anti-infective therapy in SOT recipients.

IntroductionWe investigated humoral and T-cell responses within 12 months after first BNT162b2 vaccine in solid organ transplant (SOT) recipients and controls who had received at least three vaccine doses. Furthermore, we compared the immune response in participants with and without previous SARS-CoV-2 infection.MethodsWe included adult liver, lung, and kidney transplant recipients, and controls were selected from a parallel cohort of healthcare workers.ResultsAt 12th-month, the IgG geometric mean concentrations (GMCs) (P&lt;0.001), IgA GMCs (P=0.003), and median IFN-γ (P&lt;0.001) were lower in SOT recipients than in controls. However, in SOT recipients and controls with previous infection, the neutralizing index was 99%, and the IgG, and IgA responses were comparable. After adjustment, female-sex (aOR: 3.6, P&lt;0.009), kidney (aOR: 7.0, P= 0.008) or lung transplantation (aOR: 7.5, P= 0.014), and use of mycophenolate (aOR: 5.2, P=0.03) were associated with low IgG non response. Age (OR:1.4, P=0.038), time from transplantation to first vaccine (OR: 0.45, P&lt;0.035), and previous SARS-CoV-2 infection (OR: 0.14, P&lt;0.001), were associated with low IgA non response. Diabetes (OR:2.4, P=0.044) was associated with T-cell non response.ConclusionIn conclusion, humoral and T-cell responses were inferior in SOT recipients without previous SARS-CoV-2 infection but comparable to controls in SOT recipients with previous infection.