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Objective: Limited data suggest intensive care unit (ICU) outcomes have improved in people with HIV (PWH). We describe trends in in-ICU/in-hospital mortality among PWH following admission to ICU in a single UK-based HIV referral centre, from 1 January 2000 to 31 December 2019., Methods: Modelling of associations between ICU admission and calendar year of admission was done using logistic regression with adjustment for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, CD4 + T-cell count and diagnosis of HIV at/within the past 3 months., Results: Among 221 PWH (71% male, median [interquartile range (IQR)] age 45 years [38-53]) admitted to ICU, median [IQR] APACHE II score and CD4 + T-cell count were 19 [14-25] and 122 cells/μl [30-297], respectively; HIV-1 viral load was ≤50 copies/ml in 46%. The most common ICU admission diagnosis was lower respiratory tract infection (30%). In-ICU and in-hospital, mortality were 29 and 38.5%, respectively. The odds of in-ICU mortality decreased over the 20-year period by 11% per year [odds ratio (OR): 0.89 (95% confidence interval (CI): 0.84-0.94)] with in-hospital mortality decreasing by 14% per year [0.86 (0.82-0.91)]. After adjusting for patient demographics and clinical factors, both estimates were attenuated, however, the odds of in-hospital mortality continued to decline over time [in-ICU mortality: adjusted OR: 0.97 (0.90-1.05); in-hospital mortality: 0.90 (0.84-0.97)]., Conclusion: Short-term mortality of critically ill PWH admitted to ICU has continued to decline in the ART era. This may result from changing indications for ICU admission, advances in critical care and improvements in HIV-related immune status., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We investigated differences in all-cause hospitalization between key demographic groups among people with HIV in the UK in the current antiretroviral therapy (ART) era., Design/methods: We used data from the Royal Free HIV Cohort study between 2007 and 2018. Individuals were classified into five groups: MSM, Black African men who have sex with women (MSW), MSW of other ethnicity, Black African women and women of other ethnicity. We studied hospitalizations during the first year after HIV diagnosis (Analysis-A) separately from those more than one year after diagnosis (Analysis-B). In Analysis-A, time to first hospitalization was assessed using Cox regression adjusted for age and diagnosis date. In Analysis-B, subsequent hospitalization rate was assessed using Poisson regression, accounting for repeated hospitalization within individuals, adjusted for age, calendar year, time since diagnosis., Results: The hospitalization rate was 30.7/100 person-years in the first year after diagnosis and 2.7/100 person-years subsequently; 52% and 13% hospitalizations, respectively, were AIDS-related. Compared with MSM, MSW and women were at much higher risk of hospitalization during the first year [aHR (95% confidence interval, 95% CI): 2.7 (1.7-4.3), 3.0 (2.0-4.4), 2.0 (1.3-2.9), 3.0 (2.0-4.5) for Black African MSW; other ethnicity MSW; Black African women; other ethnicity women respectively, Analysis-A] and remained at increased risk subsequently [corresponding aIRR (95% CI): 1.7 (1.2-2.4), 2.1 (1.5-2.8), 1.5 (1.1-1.9), 1.7 (1.2-2.3), Analysis-B]., Conclusion: In this setting with universal healthcare, substantial variation exists in hospitalization risk across demographic groups, both in early and subsequent periods after HIV diagnosis, highlighting the need for targeted interventions., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To describe the spectrum of kidney disease in African patients with HIV and tuberculosis (TB)., Methods: We used data from three cohorts: consecutive patients with HIV/TB in South London (UK, 2004-2016; n = 95), consecutive patients with HIV/TB who underwent kidney biopsy in Cape Town (South Africa, 2014-2017; n = 70), and consecutive patients found to have HIV/TB on autopsy in Abidjan (Cote d'Ivoire, 1991; n = 100). Acute kidney injury (AKI) was ascertained using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. In the Cape Town cohort, predictors of recovery of kidney function at 6 months were assessed using Cox regression., Results: In the London cohort, the incidence of moderate/severe AKI at 12 months was 15.1 (95% CI 8.6-26.5) per 100 person-years, and the prevalence of chronic and end-stage kidney disease (ESKD) 13.7 and 5.7%, respectively. HIV-associated nephropathy (HIVAN) was diagnosed in 6% of patients in London, and in 6% of autopsy cases in Abidjan. Evidence of renal TB was present in 60% of autopsies in Abidjan and 61% of kidney biopsies in Cape Town. HIVAN and acute tubular necrosis (ATN) were also common biopsy findings in Cape Town. In Cape Town, 40 patients were dialyzed, of whom 28 (70%) were able to successfully discontinue renal replacement therapy. Antiretroviral therapy status, CD4 cell count, estimated glomerular filtration rate (eGFR) at biopsy and renal histology, other than ATN, were not predictive of eGFR recovery., Conclusion: Kidney disease was common in Africans with HIV/TB. Monitoring of kidney function, and provision of acute dialysis to those with severe kidney failure, is warranted.

Among an inner London UK cohort of 147 adolescents transitioning from paediatric into adult care between 2007 and 2015, a new diagnosis of lymphoma was made in five patients; incidence rate = 0.425/100 person-years (95% confidence interval = 0.424-0.426). Previously described risk factors, including low nadir CD4 cell count and ongoing HIV-1 viraemia, appeared to be important. These data suggest that careful surveillance and a low threshold for investigating relevant symptoms continue to be essential for such patients.

Objective: Despite biological advantages of male circumcision in reducing HIV/sexually transmitted infection acquisition, concern is often expressed that it may reduce sexual enjoyment and function. We examine the association between circumcision and sexual function among sexually active men in Britain using data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Natsal-3 asked about circumcision and included a validated measure of sexual function, the Natsal-SF, which takes into account not only sexual difficulties but also the relationship context and overall level of satisfaction., Methods: A stratified probability survey of 6293 men and 8869 women aged 16-74 years, resident in Britain, undertaken 2010-2012, using computer-assisted face-to-face interviewing with computer-assisted self-interview for the more sensitive questions. Logistic regression was used to calculate odds ratios (ORs) to examine the association between reporting male circumcision and aspects of sexual function among sexually active men (n = 4816)., Results: The prevalence of male circumcision in Britain was 20.7% [95% confidence interval (CI): 19.3-21.8]. There was no association between male circumcision and, being in the lowest quintile of scores for the Natsal-SF, an indicator of poorer sexual function (adjusted OR: 0.95, 95% CI: 0.76-1.18). Circumcised men were as likely as uncircumcised men to report the specific sexual difficulties asked about in Natsal-3, except that a larger proportion of circumcised men reported erectile difficulties. This association was of borderline statistical significance after adjusting for age and relationship status (adjusted OR: 1.27, 95% CI: 0.99-1.63)., Conclusion: Data from a large, nationally representative British survey suggest that circumcision is not associated with men's overall sexual function at a population level.

Background and Objectives: Tuberculosis (TB) is a leading cause of death in HIV-infected patients worldwide. We aimed to study clinical characteristics and outcome of 1075 consecutive patients diagnosed with HIV/TB from 2004 to 2006 in Europe and Argentina., Methods: One-year mortality was assessed in patients stratified according to region of residence, and factors associated with death were evaluated in multivariable Cox models., Results: At TB diagnosis, patients in Eastern Europe had less advanced immunodeficiency, whereas a greater proportion had a history of intravenous drug use, coinfection with hepatitis C, disseminated TB, and infection with drug-resistant TB (P < 0.0001). In Eastern Europe, fewer patients initiated TB treatment containing at least rifamycin, isoniazid, and pyrazinamide or combination antiretroviral therapy (P < 0.0001). Mortality at 1 year was 27% in Eastern Europe, compared with 7, 9 and 11% in Central/Northern Europe, Southern Europe, and Argentina, respectively (P < 0.0001). In a multivariable model, the adjusted relative hazard of death was significantly lower in each of the other regions compared with Eastern Europe: 0.34 (95% confidence interval 0.17-0.65), 0.28 (0.14-0.57), 0.34 (0.15-0.77) in Argentina, Southern Europe and Central/Northern Europe, respectively. Factors significantly associated with increased mortality were CD4 cell count less than 200 cells/microl [2.31 (1.56-3.45)], prior AIDS [1.74 (1.22-2.47)], disseminated TB [2.00 (1.38-2.85)], initiation of TB treatment not including rifamycin, isoniazid and pyrazinamide [1.68 (1.20-2.36)], and rifamycin resistance [2.10 (1.29-3.41)]. Adjusting for these known confounders did not explain the increased mortality seen in Eastern Europe., Conclusion: The poor outcome of patients with HIV/TB in Eastern Europe deserves further study and urgent public health attention.

Objective: The cellular innate immune response to HIV-1 is poorly characterized. In view of HIV-1 tropism for macrophages, which can be activated via pattern recognition receptors to trigger antimicrobial defences, we investigated innate immune responses to HIV-1 by monocyte-derived macrophages., Design: In a model of productive HIV-1 infection, cellular innate immune responses to HIV-1 were investigated, at the level of transcription factor activation, specific gene expression and genome-wide transcriptional profiling. In addition, the viral determinants of macrophage responses and the physiological effect of innate immune cellular activation on HIV-1 replication were assessed., Results: Productive HIV-1 infection did not activate nuclear factor-kappaB and interferon regulatory factor 3 transcription factors or interferon gene expression (IFN) and caused remarkably small changes to the host-cell transcriptome, with no evidence of inflammatory or IFN signatures. Evasion of IFN induction was not dependent on HIV-1 envelope-mediated cellular entry, inhibition by accessory proteins or reverse transcription of ssRNA that may reduce innate immune cellular activation by viral RNA. Furthermore, IFNbeta priming did not sensitize responses to HIV-1. Importantly, exogenous IFNbeta or stimulation with the RNA analogue poly I:C to simulate innate immune activation invoked HIV-1 restriction., Conclusion: We conclude that macrophages lack functional pattern recognition receptors for this virus and that HIV-1 tropism for macrophages helps to establish a foothold in the host without triggering innate immune cellular activation, which would otherwise block viral infection effectively.

The efficacy of boosted protease inhibitor monotherapy (BPIm) in HIV-positive patients with complex medical problems was assessed in ten patients. With BPIm, median (range) HIV viral load reduction was log10 2.15 (1.62-3.1) by 4-8 weeks; in four patients, viral load was < 400 copies/ml. During follow-up, at median (range) = 50 (8-156) weeks, no patient had an opportunistic illness; one patient developed new PI mutations after 48 weeks. These very preliminary data need further confirmation on a larger scale.

Objectives: The study tests the hypothesis that monocyte derived dendritic cells from HIV-1 infected individuals are normal and can restore impaired CD4 T-cell antigen specific responses., Design: Monocyte derived dendritic cells were isolated from individuals at three different stages of HIV-1 infection with a wide spectrum of viral load and CD4 T-cell counts, and from healthy volunteers. The cell surface phenotype and allogeneic stimulatory potential of these dendritic cells was documented. CD4 T-cell responses to HIV p24, tetanus toxoid and purified protein derivative were measured using either unfractionated peripheral blood mononuclear cells, or purified dendritic cell/T-cell cultures., Results: Dendritic cells from all three HIV-1 infected groups did not differ from each other or from healthy volunteers in terms of cell surface phenotype or allogeneic stimulatory potential using T cells from healthy volunteers. Dendritic cells from immunosuppressed antiretroviral naive individuals enhanced the autologous recall proliferative responses both to HIV-1 p24, and third party antigens tetanus toxoid and purified protein derivative, both in terms of the proportion of responding individuals, and median proliferation., Conclusion: Antigen presentation by dendritic cells partially restores impaired antigen specific CD4 T-cell responses associated with HIV-1 infection. Immunization strategies which target dendritic cells may therefore offer significant advantages in the ability to stimulate HIV-specific protective immune responses.

This study examines the utility of resistance testing during treatment interruption, making comparisons with the current IAS guidelines. A total of 188/1279 tests (14%) were performed during treatment interruption; 69/188 tests (36.7%) demonstrated key mutations. Time off therapy and the total number of previous drugs were both significantly associated with the presence of mutations. We conclude that resistance testing is of value up to 3 months after treatment interruption, and may convey some benefit up to 12 months.

The performance characteristics of the enzyme-linked immunospot assay (ELISPOT) assay (T-SPOT TB) for the diagnosis of latent tuberculosis infection in HIV-infected individuals are unknown. Given that ELISPOT enumerates Mycobacterium tuberculosis antigen-specific IFN-gamma-secreting T cells, HIV-associated immunosuppression might adversely affect test performance. However, we found that 28 out of 29 HIV-positive individuals (97%) gave evaluable test results, and performance was independent of the CD4 T-cell count. ELISPOT test performance appears to be independent of HIV-associated immunosuppression.

Objective: To determine whether proton magnetic resonance spectroscopy (MRS) demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected individuals., Design: Both prospective and retrospective cross-sectional analyses of MRS in asymptomatic HIV-infected individuals., Setting: Two specialists HIV/AIDS outpatient facilities in London., Participants: Eighty-four HIV-1 seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high-risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV infection as controls., Main Outcome Measures: Single voxel, gradient-localized proton MRS performed at 1.5 T with 135 msec echo-time and 1,600 msec repeat-time in an 8 ml volume of interest positioned in the parieto-occipital white matter. Spectroscopic results were expressed as ratios between the areas under the N-acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks., Results: There were no differences between those controls at high and those at low-risk for HIV infection. Comparing the combined control groups with the asymptomatic seropositive patients there were statistically significant differences in NA/Cho, NA/Cr (both P < 0.05) and NA/(NA + Cho + Cr) (P < 0.01)., Conclusion: Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during asymptomatic HIV-1 infection.

The polymerase chain reaction (PCR) was used to detect HIV-1 sequences (gag, pol, and env) in the cerebrospinal fluid (CSF) and serum samples from 53 HIV-1-positive patients and the results correlated with clinical evidence of neurological disease. Twenty-three out of 24 patients with neurological disease had HIV-1-specific sequences in CSF compared with four out of 20 asymptomatic patients who had no evidence of neurological involvement. The detection of HIV RNA sequences by PCR in the CSF of HIV-positive patients may provide early, rapid and direct evidence of neurological involvement in asymptomatic subjects.

The treatment of patients with AIDS and AIDS-related complex (ARC) with zidovudine is limited by major haematological toxicity. In an open study of the use of zidovudine, 10 out of a total of 81 patients developed a severe anaemia within the first 3 months of treatment. In five of these 10 patients the mean cell volume did not increase but remained within the normal range. Bone marrow examination of three of these five showed a pure red-cell aplasia. In all five patients the anaemia resolved on discontinuation of the drug and in three that were re-challenged, the anaemia recurred. Zidovudine-induced anaemia has usually been reported as macrocytic and megaloblastic, but in our experience erythroid aplasia appears to be a major cause of anaemia occurring within the first 3 months of treatment. The earliest sign is anaemia with a stable or only a slight increase in the mean cell volume (MCV).