Search

Objectives: HIV virological failure remains a major threat to programme success in sub‐Saharan Africa. While HIV drug resistance (HIVDR) and inadequate adherence are the main drivers of virological failure, the individual, clinical and health system characteristics that lead to poor outcomes are not well understood. The objective of this paper is to identify those characteristics among people failing first‐line antiretroviral therapy (ART). Methods: We enrolled a cohort of adults in HIV care experiencing virological failure on first‐line ART at five sites and used standard statistical methods to characterize them with a focus on three domains: individual/demographic, clinical, and health system, and compared each by country of enrolment. Results: Of 840 participants, 51% were women, the median duration on ART was 3.2 years [interquartile range (IQR) 1.1, 6.4 years] and the median CD4 cell count prior to failure was 281 cells/µL (IQR 121, 457 cells/µL). More than half of participants [53%; 95% confidence interval (CI) 49–56%] stated that they had > 90% adherence and 75% (95% CI 72–77%) took their ART on time all or most of the time. Conversely, the vast majority (90%; 95% CI 86–92%) with a completed genotypic drug resistance test had any HIV drug resistance. This population had high health system use, reporting a median of 3 (IQR 2.6) health care visits and a median of 1 (IQR 1.1) hospitalization in the preceding 6 months. Conclusions: Patients failing first‐line ART in sub‐Saharan Africa generally report high rates of adherence to ART, have extremely high rates of HIV drug resistance and utilize significant health care resources. Health systems interventions to promptly detect and manage treatment failure will be a prerequisite to establishing control of the HIV epidemic. [ABSTRACT FROM AUTHOR]

Objectives: Despite recent pharmacological progress, memory impairment is still frequently reported in people living with HIV. We aimed to conduct a systematic literature review investigating the presence of impairment of (sub)components of memory function in patients prescribed highly active antiretroviral therapy (ART). Methods: We adopted a cognitive neuropsychological model of memory function as the theoretical framework, distinguishing between a short‐term working memory component and a long‐term component of memory, along with their specific (sub)components. We systematically searched for the presence of impairment of each (sub)component in the selected papers. Careful consideration was given to study design and methods and control of covariates. Results: Only the central executive component of working memory has been consistently reported to be impaired in HIV infection. The other two (sub)components, namely the phonological loop and the visuospatial sketchpad, were unimpaired. Discordant results have been obtained as to verbal and visual episodic memory, as some authors reported an association with HIV infection, whereas others did not. There is little evidence for semantic memory deficit in HIV infection, while there are suggestions that the neural substrate of implicit memory may be damaged by the effects of HIV infection and inflammation. Most studies in this area have been conducted in small samples and with poor control for covariates. Thus, conclusions regarding the association of memory dysfunction with HIV infection are hampered by methodological issues such as selection bias and unmeasured confounding. Conclusions: The task remains for future research to ascertain the impact of HIV infection on memory function. [ABSTRACT FROM AUTHOR]

When modeling longitudinal data, the true values of time-varying covariates may be unknown because of detection-limit censoring or measurement error. A common approach in the literature is to empirically model the covariate process based on observed data and then predict the censored values or mismeasured values based on this empirical model. Such an empirical model can be misleading, especially for censored values since the (unobserved) censored values may behave very differently than observed values due to the underlying data-generation mechanisms or disease status. In this paper, we propose a mechanistic nonlinear covariate model based on the underlying data-generation mechanisms to address censored values and mismeasured values. Such a mechanistic model is based on solid scientific or biological arguments, so the predicted censored or mismeasured values are more reasonable. We use a Monte Carlo EM algorithm for likelihood inference and apply the methods to an AIDS dataset, where viral load is censored by a lower detection limit. Simulation results confirm that the proposed models and methods offer substantial advantages over existing empirical covariate models for censored and mismeasured covariates. [ABSTRACT FROM AUTHOR]

Introduction: Immune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non‐AIDS‐related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long‐term follow‐up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all‐cause mortality in people living with HIV (PLWH) from Latin America following ART initiation. Methods: Retrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug‐based combination therapy and with medical follow‐up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T‐cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3). Primary outcomes included all‐cause mortality, AIDS‐defining events and non‐communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T‐cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link. Results: In our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow‐up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T‐cell count) and older age were risk factors for all‐cause mortality. We also found that older age, male sex and higher baseline CD4 T‐cell count were associated with lower CD4 count increase following therapy initiation. Conclusions: Our study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow‐up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival. [ABSTRACT FROM AUTHOR]

Aims: To describe stroke syndromes and transcranial Doppler (TCD) findings in children with human immunodeficiency virus (HIV) and examine the associations between TCD and clinical and laboratory data.Method: We enrolled 42 children (24 males, 18 females) with HIV (median age=7y 6mo; 2y 7mo-15y 6mo), with and without stroke who underwent a TCD examination of the anterior and posterior circulations to derive time-averaged maximum mean velocity (TAMMV) measurements for comparison with previous studies. Clinical and laboratory variables were extracted from the medical records.Results: Of the 42 children with HIV, five had right-sided hemiparesis, three had chronic lung disease, two occurred post-varicella infection, one after herpetic oral ulceration, and one had a poorly functioning left ventricle. Neuroimaging showed middle cerebral artery (MCA) TAMMV greater than 200cm/s, moyamoya-like arteriopathy, left basal ganglia infarction with ipsilateral stenosis, hygroma consistent with venous thrombosis, and a hyperdense left MCA. Eight neurologically asymptomatic children had atypical TCD. The CD4 cell count was non-significantly lower in 6 out of 30 children with atypical TCD (median=21.5; interquartile range=16.1-26.5) compared with the remainder (median=29; interquartile range=21.3-35.0; p=0.09).Interpretation: A variety of stroke syndromes occur in children with HIV. TCD suggests atypical intracranial vessels and/or haemodynamics in some children with HIV infection, consistent with vasculopathy, possibly related directly to immunodeficiency and/or infection.What This Paper Adds: A range of stroke syndromes are found in children with human immunodeficiency virus (HIV). Transcranial Doppler (TCD) velocities in HIV are commonly outside the range for typically developing children. TCD and neuroimaging data in children with HIV suggest intracranial vasculopathy as one mechanism for stroke. CD4 cell count is non-significantly lower in children with HIV and atypical TCD. [ABSTRACT FROM AUTHOR]

Objectives The aim of the paper was to describe the association of religion with HIV outcomes in newly diagnosed Africans living in London. Methods A survey of newly diagnosed HIV-positive Africans attending 15 HIV treatment centres across London was carried out between April 2004 and February 2006. Confidential self-completed questionnaires were used, linked to clinical records. Bivariate analyses were conducted to ascertain whether religious beliefs were associated with late diagnosis, antiretroviral therapy, and immunological and virological outcome 6 months post diagnosis. Results A total of 246 Black Africans were eligible and included in the analysis: 62.6% were women, and the median age was 34 years. The median CD4 count at diagnosis was 194 cells/ μL (range 0-1334 cells/ μL) and 75.6% presented late, as defined as a CD4 count < 350 cells/ μL. Most participants were religious: non- Roman Catholic Christians (55.7%), Roman Catholics (35.2%) and Muslims (6.1%). Only 1.2% stated that they did not have a religion. Participants who attended religious services at least monthly were more likely to believe that 'faith alone can cure HIV' than those who attended less frequently (37.7% vs. 15.0%; P = 0.002). A small proportion (5.2%) believed that taking antiretroviral therapy implied a lack of faith in God. Bivariate analysis found no relationship between religiousness (as measured using frequency of attendance at religious services and religious attitudes or beliefs) and late diagnosis, changes in CD4 count/viral load 6 months post diagnosis, or initiation of antiretroviral therapy. Conclusions Strong religious beliefs about faith and healing are unlikely to act as a barrier to accessing HIV testing or antiretroviral treatment for Black Africans living in London. [ABSTRACT FROM AUTHOR]

Recurrent events are commonly encountered in biomedical studies. In many situations, there exist terminal events, such as death, which are potentially related to the recurrent events. Joint models of recurrent and terminal events have been proposed to address the correlation between recurrent events and terminal events. However, there is a dearth of suitable methods to rigorously investigate the causal mechanisms between specific exposures, recurrent events, and terminal events. For example, it is of interest to know how much of the total effect of the primary exposure of interest on the terminal event is through the recurrent events, and whether preventing recurrent event occurrences could lead to better overall survival. In this work, we propose a formal causal mediation analysis method to compute the natural direct and indirect effects. A novel joint modeling approach is used to take the recurrent event process as the mediator and the survival endpoint as the outcome. This new joint modeling approach allows us to relax the commonly used "sequential ignorability" assumption. Simulation studies show that our new model has good finite sample performance in estimating both model parameters and mediation effects. We apply our method to an AIDS study to evaluate how much of the comparative effectiveness of the two treatments and the effect of CD4 counts on the overall survival are mediated by recurrent opportunistic infections. [ABSTRACT FROM AUTHOR]

Background: Women with HIV are more often infected with human papillomavirus (HPV) and are more prone to develop precancerous cervical lesions (squamous intraepithelial lesions, SIL) and invasive cervical cancer (ICC) than HIV‐negative women. Objective: This scoping‐review analyses the impact of HIV on HPV prevalence, incidence and evolution to SIL and ICC. Methods: We selected all PubMed systematic reviews and meta‐analyses published between January 2000 and July 2021 reporting data about HPV, cervical intraepithelial neoplasia (CIN), SIL and ICC prevalence, incidence and evolution in women with HIV. A hypothetical model comparing the history of HPV infection in HIV‐negative, combined antiretroviral therapy (cART)‐treated and ‐untreated women with HIV was built. Results: Data from 11 meta‐analyses and 10 systematic reviews were selected, which included between 770 and 236 127 women with HIV. Women with HIV have a 3 to 6 times higher risk of being infected by HPV, of progression to high‐grade SIL (HSIL) and to ICC. These risks are exacerbated when the CD4 cell counts are low and when they are not using cART, whereas these risks are reduced by 20%–30% when they are optimally treated with cART and have had a suppressed HIV viral load for at least 2 years. In our model, we illustrated that optimal HIV treatment and preventing HIV reduce the number of ICC cases by 2.5 and 6 times, respectively. Conclusions: Optimal treatment and care of HIV patients are essential to reduce their prevalence of ICC, as are preventive strategies which include HPV vaccination, cervical cancer screening strategies and treatment of HSIL. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine whether HIV infection was independently associated with frailty status and its individual components. Methods: This cross‐sectional investigation included people living with HIV (PLWH) and HIV‐negative individuals from the baseline survey of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, China. Frailty phenotype was based on five components: weight loss, low physical activity, exhaustion, weak grip strength and slow gait speed. Frailty was defined as the presence of at least three components, and prefrailty was defined as one or two components. Logistic regression models were used to analyse the factors associated with frailty and its components. Results: In all, 2475 people living with HIV (age 45.5 ± 14.9 years; 76.2% male) and 4948 HIV‐negative individuals (age 45.5 ± 14.8 years; 76.3% male) were included. Among PLWH, median CD4 count was 395 cells/μL and 78% were currently on antiretroviral therapy (ART). Frailty and prefrailty were significantly more prevalent in PLWH (3.2% vs 1.9% and 32.9% vs 27.9%) overall and at ages 18–39 (1.4% vs 0.2% and 22.7% vs 19.0%), 40–59 (2.5% vs 0.9% and 30.9% vs 27.9%) and 60–90 years (8.4% vs 7.4% and 57.1% vs 45.8%). HIV infection was associated with frailty and prefrailty [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.06–2.08; and aOR = 1.18, 95% CI: 1.05–1.33, respectively] after adjusting for confounding variables, but were strengthened with further adjustment for multimorbidity (aOR = 1.62, 95% CI: 1.14–2.28; and aOR = 1.22, 95% CI: 1.09–1.37), and were no longer significant with further adjustment for depressive symptoms and sleep disorders (aOR = 1.02, 95% CI: 0.71–1.46; and aOR = 1.06, 95% CI: 0.94–1.20). Among individual components, HIV infection was positively associated with weak grip strength and slow gait speed, but negatively associated with low physical activity and exhaustion in all the adjusted models described. Conclusions: Frailty and prefrailty occur more often and earlier in PLWH. However, grip strength and gait speed are affected to a greater extent, highlighting their potential as screening and intervention targets to prevent or slow frailty among PLWH. [ABSTRACT FROM AUTHOR]

Joint models for longitudinal and time-to-event data are particularly relevant to many clinical studies where longitudinal biomarkers could be highly associated with a time-to-event outcome. A cutting-edge research direction in this area is dynamic predictions of patient prognosis (e.g., survival probabilities) given all available biomarker information, recently boosted by the stratified/personalized medicine initiative. As these dynamic predictions are individualized, flexible models are desirable in order to appropriately characterize each individual longitudinal trajectory. In this paper, we propose a new joint model using individual-level penalized splines (P-splines) to flexibly characterize the coevolution of the longitudinal and time-to-event processes. An important feature of our approach is that dynamic predictions of the survival probabilities are straightforward as the posterior distribution of the random P-spline coefficients given the observed data is a multivariate skew-normal distribution. The proposed methods are illustrated with data from the HIV Epidemiology Research Study. Our simulation results demonstrate that our model has better dynamic prediction performance than other existing approaches. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, a reduction in the life expectancy gap between people living with HIV (PLWH) and the general population has been observed, irrespective of CD4 lymphocyte count, due to widespread access to antiretroviral treatment. The increase in the life expectancy of PLWH has increased awareness of both the ageing process and gender discrepancies in immune restoration and survival. Materials and Methods: Longitudinal data were collected for 2240 patients followed up at the Hospital for Infectious Diseases in Warsaw, Poland (n = 1482), and the Department of Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland (n = 758). Immune restoration was measured from the time of starting combination antiretroviral therapy until achieving 500 CD4 lymphocytes/μL, 800 CD4 lymphocytes/μL, and CD4/CD8 lymphocyte ratios of > 0.8 and > 1.0. Full recovery was achieved when the patient was restored to both 800 CD4 lymphocytes/μL and a CD4/CD8 lymphocyte ratio > 1.0. Results: For all endpoints, immune restoration had a protective effect by reducing mortality. Patients who achieved immune restoration had a greater chance of reduced mortality than those who did not achieve immune restoration: for CD4 count > 500 cells/μL, HR = 5.4 (interquartile range: 3.09–9.41), p < 0.001; for CD4 > 800 cells/μL, HR = 5.37 (2.52–11.43), p < 0.001; for CD4/CD8 ratio > 0.8, HR = 3.16 (1.81–5.51), p < 0.001; for CD4/CD8 ratio > 1.0, HR = 2.67 (1.49–5.24), p = 0.001, and for full immune recovery, HR = 3.62 (1.63–8.04), p = 0.002. Conclusions: Immune restoration remains a powerful factor in improving the survival of PLWH, regardless of the speed of recovery. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the immunogenicity to SARS‐CoV‐2 and evasive subvariants BA.4/5 in people living with HIV (PLWH) following a third booster shot of inactivated SARS‐CoV‐2 vaccine. We conducted a cross‐sectional study in 318 PLWH and 241 healthy controls (HC) using SARS‐CoV‐2 immunoassays. Vaccine‐induced immunological responses were compared before and after the third dose. Serum levels of IgG anti‐RBD and inhibition rate of NAb were significantly elevated at the "post‐third dose" sampling time compared with the pre‐third dose in PLWH, but were relatively decreased in contrast with those of HCs. Induced humoral and cellular responses attenuated over time after triple‐dose vaccination. The neutralizing capacity against BA.4/5 was also intensified but remained below the positive inhibition threshold. Seropositivity of SARS‐CoV‐2‐specific antibodies in PLWH was prominently lower than that in HC. We also identified age, CD4 cell counts, time after the last vaccination, and WHO staging type of PLWH as independent factors associated with the seropositivity of antibodies. PLWH receiving booster shot of inactivated vaccines generate higher antibody responses than the second dose, but lower than that in HCs. Decreased anti‐BA.4/5 responses than that of WT impede the protective effect of the third dose on Omicron prevalence. [ABSTRACT FROM AUTHOR]

HIV‐associated infective native aortic aneurysms (INAA) constitute a subcategory of the disease INAA. This is a very rare group of patients. The aim of this systematic literature review was to compile a description of patient characteristics with HIV‐associated INAA. A systematic literature review was performed using the search terms HIV and aortic aneurysm in Ovid MEDLINE and Embase databases, on articles published between 1981 and 2022. Using the Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) statement, articles were scrutinized according to a predefined protocol including age, sex, comorbidities, microbiological pathogens, CD4‐count, HIV/AIDS state, aortic segment involved, treatment and outcome. Thirty‐three studies, all case reports with a total of 39 patients, were included. The median age was 48 years (range 27–79), most were male n = 35 (90%), and the median follow‐up was n = 6 months (range 0–63). Cardiovascular comorbidity was present in n = 1 (3%), median CD4‐count was 216 (range 6–1236), and n = 12 (31%) had AIDS. The most common microbiological pathogens were Treponema pallidum, n = 12 (31%), Salmonella spp. n = 10 (26%), Mycobacterium species n = 5 (12%) and Staphylococcal spp. n = 5 (13%). The HIV‐associated INAAs were localized in the abdominal aorta n = 32 (82%), in the thoracic aorta n = 5 (13%) and in the thoraco‐abdominal aorta n = 2 (5%). Open surgery was performed in n = 23 (59%) patients, endovascular aortic repair n = 6 (15%), and n = 7 (18%) did not receive surgery. Infection‐related complications were reported in n = 2 (7%) patients, both with postoperative development of fatal sepsis. Patients with HIV‐associated INAAs were younger, had lower rate of cardiovascular comorbidity, demonstrated low CD4 counts as a measure of immunosuppression, and demonstrated diverse microbiological pathogens compared with other INAAs. Treponema pallidum and Mycobacterium spp. were common pathogens, which are very rare microbiological pathogens in other INAAs. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to analyse patients newly diagnosed with HIV who were originally admitted to hospitals with suspicion of COVID‐19. Methods: This was a retrospective case series undertaken at four sites. Only adults with new HIV diagnosis and COVID‐19 exclusion hospitalized in 2020–2021 were included. Demographic, clinical and laboratory data were collected from medical records. Results: Twenty‐five patients were included in the analysis: 19 men (76%), 11 of Ukrainian origin (44%). The median age was 38.5 years (range 25–59). The mode of HIV transmission was heterosexual for 11 (44%) patients, eight (32%) were men who have sex with men and three (12%) were people who inject drugs. The median duration of symptoms prior to hospital presentation was 20.6 days (range 3–90). The median number of SARS‐CoV‐2 tests per patient was 2.62 (range 1–7). All SARS‐CoV‐2 tests were negative. Screening for HIV was performed on average on the 18th day of hospitalization (range 1–36 days). Twenty‐three patients (92%) were late presenters, 22 (88%) had advanced disease, and 19 (76%) were in the AIDS stage. The median CD4 T‐cell count was 72 cells/μL (range 3–382). The rate of positive HIV testing at the two sites where it was available for people with suspected COVID‐19 was 0.13% (7/5458 during the study period). Conclusions: We strongly recommend introducing the HIV screening test in the diagnostic algorithm for every patient suspected of having COVID‐19, presenting with clinical and/or radiological pulmonary symptoms. [ABSTRACT FROM AUTHOR]

Background: We investigated the effect of HIV on COVID‐19 outcomes with attention to selection bias due to differential testing and comorbidity burden. Methods: This was a retrospective cohort analysis using four hierarchical outcomes: positive SARS‐CoV‐2 test, COVID‐19 hospitalization, intensive care unit (ICU) admission and hospital mortality. The effect of HIV status was assessed using traditional covariate‐adjusted, inverse probability‐weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV‐IPWs) and combined models. Among people living with HIV (PWH), we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did and those who did not develop study outcomes using receiver operating characteristic analysis. Results: Between March and November 2020, 63 319 people were receiving primary care services at the University of California San Diego (UCSD), of whom 4017 were PWH. The PWH had 2.1 times the odds of a positive SARS‐CoV‐2 test compared with those without HIV after weighting for potential testing bias, comorbidity burden and HIV‐IPW [95% confidence interval (CI): 1.6–2.8]. Relative to people without HIV, PWH did not have an increased rate of COVID‐19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR) = 0.5, 95% CI: 0.1–1.4]. PWH did not have a different rate of ICU admission (aIRR = 1.08, 95% CI: 0.31–3.80) or of in‐hospital death (aIRR = 0.92, 95% CI: 0.08–10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. Conclusions: People living with HIV have a higher risk of COVID‐19 diagnosis than those without HIV but the outcomes are similar in both groups. [ABSTRACT FROM AUTHOR]

Introduction: People who inject drugs are at high risk of blood‐borne infections. We describe the epidemiology of HIV among people who inject drugs in England, Wales, and Northern Ireland (EW&NI) since 1981. Methods: National HIV surveillance data were used to describe trends in diagnoses (1981–2019), prevalence (1990–2019), and behaviours (1990–2019) among people who inject drugs aged ≥15 years in EW&NI. HIV care and treatment uptake were assessed among those attending in 2019. Results: Over the past four decades, the prevalence of HIV among people who inject drugs in EW&NI remained low (range: 0.64%–1.81%). Overall, 4978 people who inject drugs were diagnosed with HIV (3.2% of cases). Diagnoses peaked at 234 in 1987, decreasing to 78 in 2019; the majority were among white men born in the UK/Europe (90%), though the epidemic diversified over time. Late diagnosis (CD4 <350 cells/µl) was common (2010–2019: 52% [429/832]). Of those who last attended for HIV care in 2019, 97% (1503/1550) were receiving HIV treatment and 90% (1375/1520) had a suppressed viral load (<200 copies/ml). HIV testing uptake has steadily increased among people who inject drugs (32% since 1990). However, in 2019, 18% (246/1404) of those currently injecting reported never testing. The proportion of people currently injecting reporting sharing needles/syringes decreased from 1999 to 2012, before increasing to 20% (288/1426) in 2019, with sharing of any injecting equipment at 37% (523/1429). Conclusion: The HIV epidemic among people who inject drugs in EW&NI has remained relatively contained compared with in other countries, most likely because of the prompt implementation of an effective national harm reduction programme. However, risk behaviours and varied access to preventive interventions among people who inject drugs indicate the potential for HIV outbreaks. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical profile and outcome of patients with HIV‐associated plasmablastic lymphoma (PBL) treated with cyclophosphamide, doxorubicin, oncovin, prednisone (CHOP) chemotherapy in a tertiary hospital in KwaZulu‐Natal, South Africa. Methods: This 12‐year retrospective clinical chart review, from 2006 to 2018, of patients with PBL treated with CHOP chemotherapy describes their clinical presentation, complete response (CR), progression‐free survival (PFS) and disease‐free survival (DFS). Response to salvage chemotherapy was also assessed, as was the overall survival (OS). Results: Of 26 patients included in the study, PBL was the presenting manifestation of underlying HIV infection in 58% (n = 15). The median age was 35 years (range 13–49), and 62% (n = 16) were males. The median CD4 count was 285 cells/µL (range 45–863). All patients had extranodal disease, with 4% having bone marrow involvement (n = 1) and > 60% presenting with advanced stage and high‐risk PBL. Central nervous system (CNS) involvement was present in 15% (n = 4). A CR was attained in 46% (n = 12). The median DFS was 23.5 months (range 5–91 months), with an overall 2‐year survival of 42% (n = 11). Conclusions: Patients with PBL had a low CR with CHOP chemotherapy and poor OS. Use of alternative chemotherapy regimens needs to be investigated to optimally manage this aggressive lymphoma. The surprisingly low incidence of marrow involvement is the focus of ongoing local research. [ABSTRACT FROM AUTHOR]

HIV prevalence among men who have sex with men in China has increased dramatically, and timely linkage to care after being diagnosed with HIV is important to treatment success. This cross‐sectional study aims to utilize structural equation modeling to test a hypothesized model of timely linkage to care adapted from the HIV‐related stigma framework. Data were collected from 257 men who have sex with men living with HIV. The proportion of participants with timely linkage to care within 1 month was 63.42%. The model result showed a good fit. Higher HIV‐related stigma was significantly associated with a lower level of social support, mental health, maladaptive coping (three mechanism variables), and attitude toward linkage to care. Higher CD4+ T‐cell count, disclosure of HIV positivity to sexual partners, and greater convenience of accessing care were related to timely linkage to care (p < 0.05). These model results suggest that enhancing attention to family reactions and social support are needed for further research and interventions to accelerate newly diagnosed people's access to HIV care in China. [ABSTRACT FROM AUTHOR]

Aim: After the hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) around 2018, the importance of HAV vaccination was emphasized, especially for MSM‐living with human immunodeficiency virus (MSM‐LWHIV). Aimmugen® is licensed and distributed exclusively in Japan. While administration of three doses is recommended, 85% of recipients in the general population were reported to acquire seroprotection after the second dose. In this study, we evaluated the efficacy of two or three vaccine doses along with predictors associated with the response to Aimmugen® in MSM‐LWHIV. Methods: We retrospectively examined anti‐HA‐IgG titers of MSM‐LWHIV vaccinated with Aimmugen® in our hospital. Patients' data were collected from medical records. Results: Between January 2018 and October 2019, 141 subjects whose median age was 46 years old, were examined. All the subjects were on antiretroviral therapy (ART) and the median CD4 count was 615/μL. The acquisition rate of protectable anti‐HA‐IgG titers after the second and third dose was 71.1% and 98.6%, respectively. In 114 subjects whose anti‐HA‐IgG titers were tested after the second‐dose, factors significantly associated with better response were prolonged ART duration and higher CD4 count. The titers of anti‐HA‐IgG after the third dose were higher in those who became seropositive after the second‐dose than those who did not. Conclusions: Three‐dose of Aimmugen® for MSM‐LWHIV was effective while two‐dose was less effective compared to non‐HIV‐infected people. People‐LWHIV with shorter duration of ART and lesser CD4 cell count achieved lower titers of anti‐HA‐IgG and might require an additional vaccination. [ABSTRACT FROM AUTHOR]

Introduction: Adolescents living with HIV are subject to multiple co‐morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. Methods: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10–17 years, were included. Growth was measured using height‐for‐age Z‐scores (HAZ, stunting if <‐2 SD, WHO growth charts). Linear mixed‐effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex‐specific models with fractional polynomials were used to model non‐linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. Results: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two‐thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub‐Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia‐Pacific; 19% overall had CD4 counts <500 cells/mm3. Across adolescence, higher HAZ was observed in females and among those in high‐income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch‐up with non‐stunted, early ART‐treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3. This decline was observed across all regions, in males and females. Conclusions: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood. [ABSTRACT FROM AUTHOR]

Objectives: Effective and safe COVID‐19 vaccines have been developed and have resulted in decreased incidence and severity of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and can decrease secondary transmission. However, there are concerns about dampened immune responses to COVID‐19 vaccination among immunocompromised patients, including people living with HIV (PLWH), which may blunt the vaccine's efficacy and durability of protection. This study aimed to assess the qualitative SARS‐CoV‐2 vaccine immunogenicity among PLWH after vaccination. Methods: We conducted targeted COVID‐19 vaccination (all received BNT162b2 vaccine) of PLWH (aged ≥ 55 years per state guidelines) at Yale New Haven Health System and established a longitudinal survey to assess their qualitative antibody responses at 3 weeks after the first vaccination (and prior to receipt of the second dose of the COVID‐19 vaccine) (visit 1) and at 2–3 weeks after the second vaccination (visit 2) but excluded patients with prior COVID‐19 infection. Our goal was to assess vaccine‐induced immunity in the population we studied. Qualitative immunogenicity testing was performed using Healgen COVID‐19 anti‐Spike IgG/IgM rapid testing. Poisson regression with robust standard errors was used to determine factors associated with a positive IgG response. Results: At visit 1, 45 of 78 subjects (57.7%) tested positive for SARS‐CoV‐2 anti‐Spike IgG after the first dose of COVID‐19 vaccine. Thirty‐nine subjects returned for visit 2. Of these, 38 had positive IgG (97.5%), including 20 of 21 subjects (95.2%) with an initial negative anti‐Spike IgG. Our bivariate analysis suggested that participants on an antiretroviral regimen containing integrase strand transfer inhibitors [relative risk (RR) = 1.81, 95% confidence interval (CI): 0.92–3.56, p = 0.085] were more likely to seroconvert after the first dose of the COVID‐19 vaccine, while those with a CD4 count < 500 cells/μL (RR = 0.59, 95% CI: 0.33–1.05, p = 0.071), and those diagnosed with cancer or another immunosuppressive condition (RR = 0.49, 95% CI: 0.18–1.28, p = 0.15) may have been less likely to seroconvert after the first dose of the COVID‐19 vaccine. The direction of these associations was similar in the multivariate model, although none of these findings reached statistical significance (RRintegrase inhibitor = 1.71, 95% CI: 0.90–3.25, p = 0.10; RRCD4 count = 0.68, 95% CI: 0.39–1.19, p = 0.18; RRcancer or another immunosuppressive condition = 0.50, 95% CI: 0.19–1.33, p = 0.16). With regard to immunogenicity, we were able to record very high rates of new seroconversion following the second dose of the COVID‐19 vaccine. Conclusions: Our study suggests that completing a two‐dose series of BNT162b2 vaccine is critical for PLWH given suboptimal seroconversion rates after the first dose and subsequent improved seroconversion rates after the second dose. [ABSTRACT FROM AUTHOR]

Background: There is currently little evidence exploring menopausal status, age at last menstrual period (LMP) and management of menopause among women living with HIV aged 45–60 years in England. Methods: Socio‐demographic, lifestyle and clinical data were collected through a self‐completed cross‐sectional survey. Longitudinal CD4 count and viral load data were available from linkage to clinical records, if consent was provided. Women were categorised as pre‐, peri‐ or post‐menopausal. Factors associated with menopausal stage were examined using ordinal logistic regression adjusting for age. Age at LMP was estimated using Kaplan–Meier survival analysis. Results: The 847 women had a median age of 49 [interquartile range (IQR): 47–52] years. Most were of black ethnicity (81.3%), were born outside the UK (85.0%) and had completed secondary education (88.7%); 177 (20.4%), 373 (43.0%) and 297 (34.2%) were pre‐, peri‐ or post‐menopausal, respectively. After adjusting for age, associations of menopausal status with non‐cohabiting relationship [adjusted odds ratio = 0.63 (95% confidence interval: 0.43–0.91)], baseline viral load ≥ 100 000 copies/mL [2.67 (1.20–5.94)] and unemployment [1.34 (0.97–1.84)] remained significant. Median (IQR) age at LMP was 54 (51–55) years in the group. In total, 27.9% (233/836) of women reported severe menopausal symptoms; 45.6% of those with somatic symptoms had heard of hormone replacement therapy and 8.7% had used it. Only 5.6% of women with urogenital symptoms had used topical oestrogen. Conclusions: Our findings highlight the importance of educating both women and their healthcare providers about menopausal symptoms and management options. [ABSTRACT FROM AUTHOR]

Introduction: Microvesicles (MVs) are bioactive, submicron‐sized (0.01‐1000 nm) membrane vesicles released from various types of cells under normal physiological and pathophysiological conditions. MVs have emerged as important mediators of cell‐to‐cell communication in a diverse range of normal and pathological processes. MVs have been recognized as potential biomarkers in coagulation, inflammation, and cancer. However, for clinical use, minimizing factors which could affect enumeration and phenotypic characterization of MVs during pre‐analytical steps is crucial. In this study, we used flow cytometry and nanoparticle tracking analysis (NTA) to investigate the impact of blood collection using with and without anticoagulant on the number and phenotype of MVs in blood samples. Methods: Blood from 30 healthy volunteers was collected by venipuncture into 3.2% sodium citrate and clot activator tubes. MV subpopulations and their concentrations were investigated using flow cytometry and NTA. MV morphology was examined by transmission electron microscopy. Results: Results showed that the concentration of MVs was significantly lower in serum than in plasma and that CD41+MV, CD41+/CD62P+MV, CD45+MV, and CD142+MV levels from serum were significantly lower than those from plasma, whereas no significant differences in Annexin V (Anx V)+ MV, CD235a+ MV, and CD144+ MV levels were found. Interestingly, serum MVs had a higher proportion of small‐sized MVs and lower proportion of large‐sized MVs than did plasma MVs. Conclusion: Although plasma samples are commonly used, our results suggest that serum can also be used in enumeration of MVs, but care must be taken if coagulation is an aspect of the research. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated an association between CD4 counts, viral load (VL), WHO staging, and caries among HIV‐positive (HIV+) children on HAART therapy (>12 months). Aim: To determine the strength of association between CD4 counts, WHO staging, VL, and dental caries. Design: This cross‐sectional analytical study comprised of 355 HIV + children, aged 4‐12 years, attending a hospital in Johannesburg, South Africa. Demographic and clinical data such as decayed (d,D), missing (m,M), filled teeth (f,F) [dmft/DMFT], CD4 counts, and WHO staging were collected. Correlation and regression analyses were done to test for associations. Results: Caries prevalence for this cohort of children was 57%. The dmft score for the primary dentition was 4.36 (SD 4.87) and DMFT for secondary dentition was 0.58 (SD 1.49). Pearson's correlation analyses showed significant association between VL and CD4 count (P =.003) and VL and WHO stage (P =.007). Weak associations were noted between caries (d, D) and VL, CD4 count, and WHO stage of disease for correlation and regression analyses. Conclusion: There appears to be no substantial evidence of any significant association between the presence of caries among HIV + children and CD4 counts, viral load, and WHO clinical stage of the disease. [ABSTRACT FROM AUTHOR]

Objectives: Plasmablastic lymphoma (PBL) is a clinically aggressive lymphoma which has a predilection for extranodal sites and is frequently HIV‐associated. The incidence of non‐Hodgkin lymphoma is thought to be reduced by widescale antiretroviral therapy (ART) coverage, but the literature is sparse as regards the impact of ART on the incidence of PBL and its outcomes in South Africa (SA). This study aimed to compare factors of interest in cases of PBL diagnosed before and after the widespread availability of ART in Johannesburg, SA. Methods: All cases of PBL diagnosed in the state sector hospitals of Johannesburg in 2007 and 2017 (before and after the widespread availability of ART, respectively) were extracted from the laboratory information system, and factors of interest compared. Results: The majority (> 95%) of cases of PBL were seen among people with HIV infection (PWH) at both time‐points, and the proportion of patients on ART and with virological suppression (VS) increased significantly in 2017. However, the number of cases of PBL did not differ significantly between the two years assessed, comprising 46/397 (11.6%) and 53/582 (9.6%) of all lymphomas in 2007 and 2017, respectively (P = 0.23). Ongoing risk for PBL among PWH with virological control and immunological recovery was evident in 2017, as 18.9% of the patients had both VS and CD4 counts > 200 cells/μL at diagnosis. Inferior survival times were associated with elevated lactate dehydrogenase (LDH) levels and Epstein Barr virus (EBV) negativity, but were not influenced by the presence of AIDS, ART or VS. EBV negativity was significantly associated with VS, and appeared to flag a particularly aggressive form of the disease. Conclusions: Widescale ART coverage has not reduced the incidence of PBL in Johannesburg, and an ongoing risk for this disease among PWH with adequate virological control and immunological recovery persists. [ABSTRACT FROM AUTHOR]

Objectives: A risk score for long‐term prediction of chronic kidney disease (CKD) in people living with HIV (PLHIV) has been developed using data from the D:A:D cohort. We assessed the performance of the D:A:D risk score in a cohort of PLHIV in West Africa. Methods: Data from PLHIV starting antiretroviral treatment in four clinics in Burkina Faso, Côte d'Ivoire and Togo participating in the IeDEA West Africa collaboration were analysed. CKD was defined as two consecutive estimated glomerular filtration rates (eGFRs) of ≤ 60 mL/min/1.73 m2. The D:A:D score (short version) was calculated using age, gender, nadir CD4 and baseline eGFR and was categorized into low, medium, and high‐risk groups. Results: In 14 930 participants (70% female, median age = 38 years; median nadir CD4 count = 183 cells/µL) followed for a median duration of 5.7 years, 660 (4.4%) progressed to CKD, with an incidence [95% confidence interval (CI)] of 7.8 (7.2–8.4) per 1000 person‐years (PY). CKD incidence rates were 2.4 (2.0–2.8), 8.1 (6.8–9.6) and, 30.9 (28.0–34.1) per 1000 PY in the low‐, medium‐ and high‐risk groups, respectively. In the high‐risk group, 14.7% (95% CI: 13.3; 16.3) had progressed to CKD at 5 years. Discrimination was good [C‐statistics = 0.81 (0.79–0.83)]. In all, 79.4% of people who progressed to CKD were classified in the medium‐ to high‐risk group at baseline (sensitivity) and 66.5% of people classified in the low risk group at baseline did not progress to CKD (specificity). Conclusions: These findings confirm the validity of the D:A:D score in identifying individuals at risk of developing CKD who could benefit from enhanced kidney monitoring in West African HIV clinics. [ABSTRACT FROM AUTHOR]

Objectives: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). Methods: We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual‐energy X‐ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. Results: In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479–800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new‐onset metabolic syndrome. Conclusions: Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Elite controllers (EC) are a rare group of HIV‐1‐positive individuals who suppress viral loads (VL) to undetectable levels with elevated CD4 T‐cell counts in the absence of ART. While rates of short‐ and mid‐term progression have been described in these patients, few studies have focused on their long‐term outcome This study aims to describe the virological and immunological behaviour in a cohort of elite controllers followed up for a median of 17 years in the University Hospital, and to identify factors that may be related to disease progression. Methods: We conducted a descriptive, prospective and single‐centre study of all HIV‐positive adults recorded in the University Hospital database who met the definition criteria for EC. EC were defined as patients having two consecutive undetectable VL without ART for at least one year. Patients were followed from baseline up to December 2019, to the development of a progression event (loss of VL control, CD4+ T cell decline, AIDS or death) or to the censoring date (lost to follow‐up or initiation of ART). Predictive models of progression were calculated. Results: Fifty‐nine EC were identified with a median follow‐up of 17 years contributing 1033 PYFU. The median (95% CI) time duration from HIV‐1 diagnosis to disease progression was four (1.7 to 6.3) years. Forty‐nine (83%) presented progression to the composite end‐point, 44 (74.6%) lost viral control, 39 (66.1%) lost immunological control, two developed AIDS and two died. Only 10 patients (16.9%) did not show progression of any kind. Independent predictors of virological progression were sexual risk of HIV‐1 acquisition and VL blips during the first year of follow‐up (baseline). The only independent predictor detected for progression to a composite end‐point was VL blips during the first year of follow‐up (baseline). Conclusions: The rate of long‐term progression in EC was very high. Only a minority of patients did not show clinical progression after a median of 17 years of follow‐up. These results should be taken in account when considering EC as a model of HIV‐1 remission. [ABSTRACT FROM AUTHOR]

Objectives: We aim to explore the safety and feasibility of umbilical cord mesenchymal stem cells (UC‐MSCs) transplantation in patients with severe and critically severe coronavirus disease‐2019 (COVID‐19). Methods: We conducted a small sample, single arm, pilot trial. In addition to standard therapy, we performed four rounds of transplantation of UC‐MSCs in sixteen patients with severe and critically severe COVID‐19. We recorded adverse events from enrolment to Day 28. We evaluated the oxygenation index, inflammatory biomarkers, radiological presentations of the disease and lymphocyte subsets count on the 7th day (D7 ± 1 day), the 14th day (D14 ± 1 day) and the 28th day (D28 ± 3 days). Results: There were no infusion‐related or allergic reactions. The oxygenation index was improved after transplantation. The mortality of enrolled patients was 6.25%, whereas the historical mortality rate was 45.4%. The level of cytokines estimated varied in the normal range, the radiological presentations (ground glass opacity) were improved and the lymphocyte count and lymphocyte subsets (CD4+ T cells, CD8+ T cells and NK cells) count showed recovery after transplantation. Conclusions: Intravenous transplantation of UC‐MSCs was safe and feasible for treatment of patients with severe and critically severe COVID‐19 pneumonia. [ABSTRACT FROM AUTHOR]

Tuberculosis is the most common cause of death in HIV-infected patients. Isoniazid is used as a first-line drug to treat tuberculosis infection. However, variability in isoniazid pharmacokinetics can result in hepatotoxicity or treatment failure. Determination of clinical factors affecting isoniazid pharmacokinetics and metabolic pathways in HIV co-infected patients is therefore critical. Plasma levels of isoniazid, acetyl-isoniazid, and isonicotinic acid from 63 patients co-infected with tuberculosis and HIV were analyzed by liquid chromatography with tandem mass spectrometry followed by nonlinear mixed-effects modeling. Patients were genotyped to determine acetylator status. Patients were either on concomitant efavirenz-based antiretroviral therapy or HIV treatment naïve. Clearances of isoniazid were 1.3-fold and 2.3-fold higher in intermediate and rapid acetylators, respectively, compared with slow acetylators. Patients on concomitant efavirenz-based antiretroviral therapy had 64% and 80% higher population predicted clearances of acetyl-isoniazid and isonicotinic acid, respectively, compared with patients who were HIV treatment naïve. Both sex and CD4 cell count affected the bioavailability of isoniazid. Variability in isoniazid exposure could be reduced by dose adaptions based on acetylator type and sex in addition to the currently used weight bands. A novel dosing strategy that has the potential to reduce isoniazid-related toxicity and treatment failure is presented. [ABSTRACT FROM AUTHOR]

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV‐status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type‐specific HPV infection in a cohort of 2,470 HIV‐positive (HIV[+]) and 895 HIV‐negative (HIV[−]) women. Semi‐annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type‐specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[−] women. HPV71 and HPV16 prevalence had the weakest associations with HIV‐status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type‐specific prevalence in HIV[−] women correlated with lower PRs (ρ = −0.59; p = 0.0001). An alternative (quadratic model) statistical approach (PHIV+ = a*PHIV− + b*PHIV−2; R2 = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[−] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[−] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common. What's new? What makes common types of human papillomavirus (HPV) common? To answer this question, the authors examined HPV types in HIV‐infected and uninfected women as the immune status in this population is quantifiable by CD4 T cell count. They found that HPV types that were most prevalent in HIV‐negative women were also the types whose prevalence was least affected by HIV infection. This relative independence from immune status supports a model that the innate ability to avoid the effects of immune surveillance makes common HPV types, in fact, common. [ABSTRACT FROM AUTHOR]

Introduction: Few studies have systematically described population‐level differences comparing men and women across the continuum of routine HIV care. This study quantifies differentials in HIV care, treatment and mortality outcomes for men and women over time in South Africa. Methods: We analysed population‐wide linked anonymized data, including vital registration linkage, for the Western Cape Province, from the time of first CD4 count. Three antiretroviral therapy guideline eligibility periods were defined: 1 January 2008 to 31 July 2011 (CD4 cell count <200 cells/µL), 1 August 2011 to 31 December 2014 (<350 cells/µL), 1 January 2015 to 31 August 2016 (<500 cells/µL). We estimated care uptake based on service attendance, and modelled associations for men and women with ART initiation and overall, pre‐ART and ART mortality. Separate Cox proportional hazard models were built for each outcome and eligibility period, adjusted for tuberculosis, pregnancy, CD4 count and age. Results: Adult men made up 49% of the population and constituted 37% of those living with HIV. In 2009, 46% of men living with HIV attended health services, rising to 67% by 2015 compared to 54% and 77% of women respectively. Men contributed <35% of all CD4 cell counts over 10 years and presented with more advanced disease (39% of all first presentation CD4 cell counts from men were <200 cells/µL compared to 25% in women). ART access was lower in men compared to women (AHR 0.79 (0.77 to 0.80) summarized for Period 2) over the entire study). Mortality was greater in men irrespective of ART (AHR 1.08 (1.01 to 1.16) Period 3) and after ART start (AHR 1.15 (1.05 to 1.20) Period 3) with mortality differences decreasing over time. Conclusions: Compared to women, men presented with more advanced disease, were less likely to attend health care services annually, were less likely to initiate ART and had higher mortality overall and while receiving ART care. People living with HIV were more likely to initiate ART if they had acute reasons to access healthcare beyond HIV, such as being pregnant or being co‐infected with tuberculosis. Our findings point to missed opportunities for improving access to and outcomes from interventions for men along the entire HIV cascade. [ABSTRACT FROM AUTHOR]

Introduction: Aiming to reach UNAIDS 90‐90‐90 targets, nearly all sub‐Saharan African countries have expanded antiretroviral therapy (ART) to all people living with HIV (PLWH) (Treat All). Few published data exist on viral load testing and viral suppression under Treat All in this region. We assessed proportions of patients with available viral load test results and who were virally suppressed, as well as factors associated with viral suppression, among PLWH in 10 Rwandan health centres after Treat All implementation. Methods: Cross‐sectional study during 2018 of adults (≥15 years) engaged in HIV care at 10 Rwandan health centres. Outcomes were being on ART (available ART initiation date in the study database, with no ART discontinuation prior to 1 January 2018), retained on ART (≥2 post‐ART health centre visits ≥90 days apart during 2018), available viral load test results (viral load measured in 2018 and available in study database) and virally suppressed (most recent 2018 viral load <200 copies/mL). We used modified Poisson regression models accounting for clustering by health centre to determine factors associated with being virally suppressed. Results: Of 12,238 patients, 7050 (58%) were female and 1028 (8%) were aged 15 to 24 years. Nearly all patients (11,933; 97%) were on ART, of whom 11,198 (94%) were retained on ART. Among patients retained on ART, 10,200 (91%) had available viral load results; of these 9331 (91%) were virally suppressed. Viral suppression was less likely among patients aged 15 to 24 compared to >49 years (adjusted prevalence ratio (aPR): 0.83, 95% CI 0.76 to 0.90 and those with pre‐ART CD4 counts of <200 compared to ≥500 cells/mm3 (aPR: 0.92, 95% CI 0.90 to 0.93). There was no statistically significant difference in viral suppression among patients who entered after Treat All implementation compared to those who enrolled before 2010 (aPR 0.98, 95% CI 0.94 to 1.03). Conclusions: In this large cohort of Rwandan PLWH receiving HIV care after Treat All implementation, patients in study health centres have surpassed the third UNAIDS 90‐90‐90 target. To ensure all PLWH fully benefit from ART, additional efforts should focus on improving ART adherence among younger persons. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have reported better immunovirological characteristics in women compared with men after HIV seroconversion. We investigated whether differences persisted under long‐term antiretroviral therapy (ART) in individuals treated since acute and early HIV‐1 infection (AHI). Methods: Data were obtained for 262 women and 1783 men enrolled between 1996 and 2017 in the French multicentre ANRS PRIMO cohort. We modelled the viral response, long‐term immune recovery and HIV DNA decay in the 143 women and 1126 men who initiated ART within the first three months of infection. Results: The participants were mostly white. The mean age was 37 years at AHI diagnosis. Pre‐ART viral loads were lower in women than men, 5.2 and 5.6 log10 copies/mL (p = 0.001). After ART initiation, women more rapidly achieved viral suppression than men (adjusted hazard ratio: 1.33, 95% confidence interval 1.09 to 1.69). They also experienced a faster increase in CD4+ T‐cell count and CD4:CD8 ratio during the first months of treatment. Sex‐related differences in CD4+ T‐cell counts were more pronounced with increasing age. This led to a sustained mean difference of 99 to 168 CD4+ T‐cells/µL depending on age between women and men at 150 months of ART. Moreover, CD4:CD8 ratio of women was higher than that of men by 0.31, at 150 months of ART. There was no statistically significant difference between sexes for the levels of HIV DNA over time (mean estimate at the last modelling point: 1.9 log10 copies/106 PBMCs after 70 months of ART for both sexes). Conclusions: The high level of immune recovery and decrease in total HIV DNA levels achieved after ART initiation during AHI reinforce the importance of early diagnosis of HIV infection and immediate ART initiation. The immunological benefit of being female increased throughout prolonged ART duration, which may give women additional protection from adverse clinical events and premature ageing. [ABSTRACT FROM AUTHOR]

Introduction: Prior to the availability of rilpivirine (RPV), patients who could not tolerate efavirenz and nevirapine (NVP) were treated with protease inhibitor (PI)‐based antiretroviral therapy (ART). Dyslipidaemia and other metabolic complications are commonly associated with PI use. This study aimed to compare the efficacy and adverse events between switching from PI‐based to RPV‐based regimen, versus continuing PI‐based regimens in HIV‐positive individuals with complete viral suppression. Methods: A randomized controlled trial was conducted in HIV‐positive individuals receiving PI‐based regimens with undetectable HIV RNA and without prior HIV drug resistance. Patients were enrolled between July and December 2017 in a university medical centre in Bangkok, Thailand. They were randomized to switch from PIs to RPV (switch group) or continue ritonavir‐boosted PI (control group). Primary endpoint was the proportion of patients with undetectable HIV RNA at 48 weeks. Changes in CD4 cell counts, lipid profiles and adverse events were also analysed. Results and discussion: A total of 84 patients were enrolled, 42 in each group. Mean age was 47.7 years and 53.6% were males. At 48 weeks, 95.2% of patients in the switch group and 92.9% of control group had maintained undetectable HIV RNA (difference rate 2.4%; 95% CI, −9.6 to 14.7). Means of CD4 cell counts were 611 and 641 cells/mm3 in switch and control groups respectively (p = 0.632). Mean changes in lipid profiles (switch vs. control groups) were: total cholesterol, −12.5 versus + 12.2 (p = 0.024); LDL, −3.4 versus + 6.2 (p = 0.040); HDL, +1.6 versus + 1.9 (p = 0.887); and triglycerides, −82.6 versus − 24.4 mg/dL (p = 0.031). The mean changes of glucose and eGFR were similar (p > 0.05) between the two groups. The mean change of ALT was significantly greater in switch group (18.2 vs. 4.0 U/L, p = 0.017). One patient in switch group had anorexia and elevated ALT at 14 weeks and completely recovered after RPV discontinuation. Conclusions: Switching PIs to RPV, in patients with complete viral suppression and without prior HIV drug resistance, sustains viral suppression and yields better lipid profiles. This finding supports its use as switching therapy in patients receiving PI‐based regimens due to intolerance to efavirenz and NVP and previous alternatives limited to PI in resource‐limited settings. [ABSTRACT FROM AUTHOR]

Background: Women in rural areas face challenges to HIV diagnosis and care, including limited access to testing and treatment facilities. Recent declines in HIV diagnosis rates among women in the United States are encouraging. However, few studies have addressed how HIV diagnosis and care differ by rurality. Methods: We analyzed National HIV Surveillance System data for women aged ≥13 years with diagnosed HIV infection. We examined diagnoses in the United States during 2010–2017. Then, for women living with diagnosed HIV in 40 jurisdictions with complete laboratory reporting, we assessed viral suppression (viral load <200 copies/mL). Analyses were stratified by rural‐urban category: rural (population <50,000), metropolitan (population 50,000‐499,000), and metropolitan statistical areas (MSA, population ≥500,000). Results: Among 64,004 women who received a diagnosis of HIV infection during 2010‐2017, 4.2% resided in a rural area, 15% resided in a metropolitan area, and 80% resided in an MSA. Rural women had the highest percentage of stage 3 infection (acquired immune deficiency syndrome) at diagnosis (rural 30%, metropolitan 27%, MSA 25%). Of 190,735 women living with diagnosed HIV, viral suppression was lower in rural areas (rural 55%, metropolitan 59%, MSA 58%). Conclusions: During 2010‐2017, most HIV diagnoses occurred among women residing in nonrural areas. However, women in rural areas had slightly higher levels of late diagnosis and lower levels of viral suppression, which might have resulted from differences in access to testing and treatment services. Interventions are needed to increase HIV testing, care, and viral suppression among women in rural areas. [ABSTRACT FROM AUTHOR]

Introduction: Lifelong antiretroviral therapy (ART) improves health outcomes for HIV‐positive individuals, but is jeopardized by irregular clinic attendance and hence poor adherence. Loss to follow‐up (LTFU) is typically defined retrospectively but this may lead to biased inferences. We assessed incidence of and factors associated with LTFU, prospectively and accounting for recurrent LTFU episodes, in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) of HIV‐positive persons in rural Tanzania. Methods: We included adults (≥15 years) enrolled in 2005 to 2016, regardless of ART status, with follow‐up through April 2017. LTFU was defined as >60 days late for a scheduled appointment. Participants could experience multiple LTFU episodes. We performed analyses based on the first (prospective) and last (retrospective) events observed during follow‐up, and accounting for recurrent LTFU episodes. Time to LTFU was estimated using cumulative incidence functions. We assessed factors associated with LTFU using cause‐specific proportional hazards, marginal means/rates, and Prentice, Williams and Peterson models. Results: Among 8087 participants (65% female, 60% aged ≥35 years, 42% WHO stage 3/4, and 47% CD4 count <200 cells/mm3), there were 8140 LTFU episodes, after which there were 2483 (31%) returns to care. One‐year LTFU probabilities were 0.41 (95% confidence interval 0.40, 0.42) and 0.21 (0.20, 0.22) considering the first and last events respectively. Factors associated with LTFU were broadly consistent across different models: being male, younger age, never married, living far from the clinic, not having an HIV‐positive partner, lower BMI, advanced WHO stage, not having tuberculosis, and shorter time since ART initiation. Associations between LTFU and pregnancy, CD4 count, and enrolment year depended on the analysis approach. Conclusions: LTFU episodes were common and prompt tracing efforts are urgently needed. We identified socio‐demographic and clinical characteristics associated with LTFU that can be used to target tracing efforts and to help inform the design of appropriate interventions. Incidence of and risk factors for LTFU differed based on the LTFU definition applied, highlighting the importance of appropriately accounting for recurrent LTFU episodes. We recommend using a prospective definition of LTFU combined with recurrent event analyses in cohorts where repeated interruptions in care are common. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the Spanish HIV/AIDS Network (CoRIS) during the years 2004–2017. Methods: We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models. Results: We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL. Conclusions: The initial assessment of HIV‐infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations. [ABSTRACT FROM AUTHOR]

Introduction: World Health Organization (WHO) guidelines have shifted over time to recommend earlier initiation of antiretroviral therapy (ART) and now encourage ART initiation on the day of HIV diagnosis, if possible. However, barriers to ART access may delay initiation in resource‐limited settings. We characterized temporal trends and other factors influencing the interval between HIV diagnosis and ART initiation among participants enrolled in a clinic‐based cohort across four African countries. Methods: The African Cohort Study enrols adults engaged in care at 12 sites in Uganda, Kenya, Tanzania and Nigeria. Participants provide a medical history, complete a physical examination and undergo laboratory assessments every six months. Participants with recorded dates of HIV diagnosis were categorized by WHO guideline era (<2006, 2006 to 2009, 2010 to 2012, 2013 to 2015, ≥2016) at the time of diagnosis. Cox proportional hazard modelling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for time to ART initiation. Results and discussion: From January 2013 to September 2019, a total of 2888 adults living with HIV enrolled with known diagnosis dates. Median time to ART initiation decreased from 22.0 months (interquartile range (IQR) 4.0 to 77.3) among participants diagnosed prior to 2006 to 0.5 months (IQR 0.2 to 1.8) among those diagnosed in 2016 and later. Comparing those same periods, CD4 nadir increased from a median of 166 cells/mm3 (IQR: 81 to 286) to 298 cells/mm3 (IQR: 151 to 501). In the final adjusted model, participants diagnosed in each subsequent WHO guideline era had increased rates of ART initiation compared to those diagnosed before 2006. CD4 nadir ≥500 cells/mm3 was independently associated with a lower rate of ART initiation as compared to CD4 nadir <200 cells/mm3 (HR: 0.32; 95% CI: 0.28 to 0.37). Age >50 years at diagnosis was independently associated with shorter time to ART initiation as compared to 18 to 29 years (HR: 1.38; 95% CI: 1.19 to 1.61). Conclusions: Consistent with changing guidelines, the interval between diagnosis and ART initiation has decreased over time. Still, many adults living with HIV initiated treatment with low CD4, highlighting the need to diagnose HIV earlier while improving access to immediate ART after diagnosis. [ABSTRACT FROM AUTHOR]

Aggressive non‐Hodgkin lymphoma (NHL) is among the most common cancers in sub‐Saharan Africa (SSA), where CHOP is standard treatment and outcomes are poor. To address this, we treated 17 newly diagnosed adult patients in Malawi with Burkitt (n = 8), plasmablastic (n = 8), and primary effusion lymphoma (n = 1) with a modified EPOCH regimen between 2016 and 2019. Twelve patients (71%) were male and the median age was 40 years (range 16‐63). Eleven (65%) were HIV infected, median CD4 count was 218 cells/µL (range 9‐460), and nine (82%) had suppressed HIV RNA < 400 copies/mL. Patients received a median of six cycles (range 2‐8) and median follow‐up was 14 months (range 2‐34) among patients still alive. Grade 3/4 neutropenia was observed in 26% of cycles and in 65% of patients. Sixteen (94%) responded to EPOCH and 10 (59%) achieved a complete response. One‐year overall survival (OS) was 62% (95% confidence interval [CI], 42%‐91%). Five patients (29%) died from progressive NHL and three (18%) from treatment‐related complications. These data suggest EPOCH with setting‐appropriate modifications may be a practical, safe, and effective option for improving high‐risk NHL outcomes in Malawi and comparable settings, which deserves further prospective evaluation. [ABSTRACT FROM AUTHOR]

Summary: Cryptococcus neoformans causes life‐threatening meningoencephalitis, particularly in human immunodeficiency virus (HIV)‐positive individuals with low CD4 levels (<100 cells/μL). Although the burden of cryptococcal meningoencephalitis (CM) in Turkey is low (0.13 cases per 100 000 persons), asymptomatic individuals at risk of cryptococcosis should be screened for antigenemia to prevent the disease and/or promote early CM diagnosis. A lateral flow assay (LFA) is used to detect Cryptococcus antigen (CrAg) in cerebrospinal fluid and serum. We determined Cryptococcus antigenemia prevalence in serum samples of HIV‐positive and HIV‐negative adult patients by using Dynamiker® CrAg‐LFA, a point‐of‐care dipstick test. Patients' demographic data, CD4 count, HIV‐RNA levels and anti‐retroviral therapy status were recorded. CrAg was detected in 28 (11%) of 254 HIV‐positive patients screened but not in 100 HIV‐negative control individuals; a significant difference was observed in the CrAg‐LFA positivity rate between HIV‐positive and HIV‐negative groups (x2 = 11.970; P < .05). In CrAg‐positive patients, the median CD4 level was 666 cells/μL (115‐1344 cells/μL), with a median viral load of 23 copies/mL (0‐3.69 × 106 copies/mL). In HIV‐positive CrAg‐negative patients, the median CD4 level was 633 cells/μL (31‐2953 cells/μL) and the median viral load was 12 copies/mL (0‐1.95 × 106 copies/mL; P > .05). Results indicate that HIV‐positive patients with both low (<200 cells/μL) and high (>200 cells/μL) CD4 counts should be screened for asymptomatic cryptococcal antigenemia. HIV‐associated asymptomatic cryptococcosis is not uncommon in Turkey, which warrants systematic screening. Updated strategies for CM prevention among HIV‐positive patients should be used even in non‐endemic countries. [ABSTRACT FROM AUTHOR]

Background: The number of men who have sex with men (MSM) living with human immunodeficiency virus (HIV) in China has increased rapidly and thus immediate highly active antiretroviral therapy (HAART) after diagnosis was implemented as a strategy to reduce the HIV transmission. Methods: MSM who were diagnosed with HIV and received HAART between 2013 to 2015 in Xi'an were divided into three groups (>350, 200‐350, and <200 cell/μL) according to their baseline CD4+ T cell count. The time of follow‐up was calculated from the first date of receiving HAART to December 31, 2016. The CD4+ T cell count was detected with 1 week before or after HAART. The plasma viral loads were tested after 1, 2, and 3 years of treatment. Results: Of 1442 subjects who received HAART, 690 (47.9%) cases were in >350 cell/μL group, whereas 400 (27.7%) cases and 352 (24.4%) cases were in the 200‐350 cell/μL group and <200 cell/μL group, respectively. After 1 year of treatment, the viral suppression rate in the <200 cell/μL group was 91.1%, which was significantly lower than the other two groups. The logistic regression results show that the >350 cell/μL group and 200‐350 cell/μL group predicted higher viral suppression rates. Conclusions: Baseline CD4+ T cell count more than 350 cell/μL can improve viral suppression among MSM living with HIV. Furthermore, to reduce the transmission risk, the treatment compliance of people living with HIV with high CD4+ T cell levels should be improved, and their diagnosis to the treatment time should be decreased. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: In terms of HIV infection, western and central Africa is the second most affected region world‐wide, and the gap between the regional figures for the testing and treatment cascade and the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90–90–90 targets is particularly worrying. We assessed the prevalence of virological suppression in patients routinely treated in 19 hospitals in Cameroon. Methods: A cross‐sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in the Centre and Littoral regions. The prevalences of virological suppression (<1000 HIV‐1 RNA copies/mL) were compared among all 19 hospitals using the χ2 test. Potential individual and health care‐related determinants of virological suppression were assessed using multivariate logistic regression models. Results: A total of 1700 patients (74% women; median age 41 years; median time on ART 3.7 years) were included in the study. The prevalence of virological suppression was 82.4% overall (95% confidence interval 80.5–84.2%). It ranged from 57.1 to 97.4% according to the individual hospital (P < 0.001). After adjustment, virological suppression was associated with age, CD4 cell count at ART initiation, disclosure of HIV status to family members, interruption of ART for more than two consecutive days, and location of patient's residence and hospital (rural/urban). These factors did not explain the heterogeneity of virological suppression between the study hospitals (P < 0.001). Conclusions: The overall prevalence of virological suppression was reassuring. Nevertheless, the heterogeneity of virological suppression among hospitals highlights that, in addition to programme‐level data, health facility‐level data are crucial in order to tailor the national AIDS programme's interventions with a view to achieving the third UNAIDS 90 target. [ABSTRACT FROM AUTHOR]

Background: Individuals aged 13–24 years undergo vast physical, cognitive, social and psychological changes. Australian data regarding clinical outcomes of those diagnosed with HIV in this age are sparse. Aim: We aimed to describe demographic factors, virologic and clinical outcomes of individuals aged 13–24 years diagnosed with human immunodeficiency virus (HIV). Methods: Patients diagnosed with HIV after 1997 in the Australian HIV Observational Database were divided into young adults, diagnosed at age <25 years (n = 223), and older adults (n = 1957). Demographic and clinical factors were compared between groups. Results: Young adults had a median age at diagnosis of 22 years (inter quartile range (IQR) 20–24) and median age at treatment initiation of 24 years (IQR 22–26). They were more likely to be female than the older cohort (21.1 vs 10.8%; P < 0.001). Men who have sex with men was the most common exposure category in both groups. CD4 count at diagnosis was significantly higher in younger than older adults (median 460 vs 400 cells/mm3, P = 0.006), whereas HIV viral load at diagnosis was lower (35 400 vs 61 659 copies/mL, P = 0.011). The rate of loss to follow up (LTFU) was higher in young adults (8.0 vs 4.3 per 100PY, P < 0.001). Young adults were more likely to have a treatment interruption compared to older adults (5.3 vs 4.0 per 100PY, P = 0.039). Rates of treatment switch, time to treatment change, and CD4 and viral load responses to treatment were similar between groups. Conclusions: Young adults were diagnosed with HIV at higher CD4 counts and lower viral loads than their older counterparts. LTFU and treatment interruption were more common highlighting the need for extra efforts directed towards retention in care and education regarding the risks of treatment interruptions. [ABSTRACT FROM AUTHOR]

Objectives: In adults with horizontally acquired HIV infection, an inverted CD4:CD8 ratio is associated with persistent immune activation, size of HIV reservoir and predicts an increased risk of non‐AIDS‐defining adverse events. Normalization of this ratio with antiretroviral therapy (ART) is suboptimal in adults, despite viral suppression, and is less well described in paediatric populations. We investigated rates of CD4:CD8 ratio recovery in children with perinatally acquired HIV infection (PaHIV) on ART. Methods: A cross‐sectional, retrospective analysis of routine clinical data in children with PaHIV (5–18 years old) attending a single UK centre was carried out. Results: CD4:CD8 normalization was seen in 62% of children on suppressive ART. A negative correlation was found between current CD4:CD8 ratio and age at start of ART. Positive correlations were found between current CD4:CD8 ratio and total time with suppressed HIV viral load and nadir CD4 counts. Multiple linear regression analysis showed that age at start of ART was significantly associated with current CD4:CD8 ratio (standardized β = −0.680; P < 0.001). Patient sex, ethnicity and antiretroviral regimen did not affect ratio recovery. Conclusions: We found higher rates of CD4:CD8 ratio normalization compared with previous adult studies. Children who started ART at a younger age were more likely to recover a normal ratio. The current policy of universal treatment for all HIV‐positive adults and children will enhance immunological normalization. [ABSTRACT FROM AUTHOR]

Objectives: To observe relationships between oral Candida status and salivary human beta‐defensin 2 and 3 (hBD‐2 and hBD‐3) levels in HIV/AIDS patients of Guangxi, China during the first year of antiretroviral therapy (ART) dynamically, and to understand the influence of ART on oral Candida status and salivary hBDs expressions. Methods: A prospective self‐controlled study was carried to observe the dynamic changes of CD4+ T cell counts, oral Candida carriages and salivary hBD‐2,3 expressions in HIV/AIDS patients during the first year of ART. A total of 90 HIV/AIDS patients were enrolled and were examined at the baseline, 3rd, 6th, 12th month of ART. Thirty healthy individuals were enrolled as control. Peripheral blood, oral rinse sample, and unstimulated whole saliva were collected to test CD4+ T cell counts, oral Candida carriages, and hBD‐2,3 expressions. Results: In the first year of ART, CD4+ T cell counts increased significantly. However, oral Candida carriages and oral candidiasis decreased significantly, and salivary hBD‐2 expressions in HIV/AIDS patients decreased gradually, salivary hBD‐3 levels were highly variable. Salivary hBD‐2 concentrations were positively related to oral Candida carriages. Conclusions: The incidence of oral candidiasis among HIV/AIDS patients gradually decreased due to the immune reconstruction of ART. Salivary defensins might play an important role in Candida‐host interaction in HIV/AIDS patients. [ABSTRACT FROM AUTHOR]

Objectives: India has the highest number of HIV‐infected adolescents in Asia, but little is known about their treatment outcomes. We assessed rates and factors associated with loss to follow‐up (LTFU) and mortality among Indian adolescents. Methods: The analysis included adolescents (10–19 years old) starting antiretroviral therapy (ART) between 2005 and 2014 at BJ Government Medical College, Pune, India. LTFU was defined as missing more than three consecutive monthly visits. The competing‐risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for LTFU, with death as the competing risk. Cox proportional hazard models were used to identify predictors of mortality. Results: Of 717 adolescents starting ART, 402 with complete data were included in the analysis. Of these, 61% were male and 80% were perinatally infected, and the median baseline CD4 count was 174 cells/μL. LTFU and mortality rates were 4.4 and 4.9/100‐person years, respectively. Cumulative LTFU incidence increased from 6% to 15% over 6 years. Age ≥ 15 years [adjusted SHR (aSHR) 2.44; 95% confidence interval (CI) 1.18–5.02] was a risk factor for LTFU. Cumulative mortality increased from 9.5% to 17.9% over 6 years. World Health Organization (WHO) stages III and IV [adjusted hazard ratio (aHR) 2.26; 95% CI: 1.14–4.48] and an increase in CD4 count by 100 cells/μL (aHR: 0.59; 95% CI: 0.43–0.83) were associated with mortality. Conclusions: A third of adolescents had been lost to follow‐up or died by follow‐up year 6. Older age was a risk factor for LTFU and advanced clinical disease for death. Strategies to improve retention counselling for older adolescents and closer clinical monitoring of all adolescents must be considered. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximize benefit both for the individual and society. It is unknown whether the initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub‐optimal adherence (<95%) during the first 12 months of ART. Methods: A prospective cohort study nested within a two‐arm cluster‐randomized trial of universal test and treat was implemented from March 2012 to June 2016 to measure the impact of ART on HIV incidence in rural KwaZulu‐Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, three and six months, and six‐monthly thereafter. We pooled data from participants in both arms and used random‐effects logistic regression models to examine the association between CD4 count at ART initiation and sub‐optimal adherence, and assessed if adherence levels were associated with virological suppression. Results: Among 900 individuals who initiated ART ≥12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm3 (234, 503); median age was 34.6 years (IQR 27.4 to 46.4) and 71.7% were female. Adherence was sub‐optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub‐optimal adherence with every 100 cells/mm3 increase in CD4 count: 1.00, 95% CI 0.95 to 1.05, for VAS, and 1.03, 95% CI 0.99 to 1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p < 0.001 for VAS; p = 0.006 for PC). Conclusions: We found no evidence that higher CD4 counts at ART initiation were associated with sub‐optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long‐term outcomes are needed. ClinicalTrials.gov NCT01509508. [ABSTRACT FROM AUTHOR]