Identification of risk factors associated with national transmission and late presentation of HIV-1, Denmark, 2009 to 2017.

BackgroundDespite availability of pre-exposure prophylaxis (PrEP), the incidence of HIV-1 in Europe remained stable the past decade. Reduction of new HIV-1 infections requires more knowledge about the profiles of high-risk transmitters and late presenters (LP).AimWe aimed to investigate risk factors associated with HIV-1 transmission clusters and late presentation with HIV-1 in Denmark.MethodsBlood samples and epidemiological information were collected from newly diagnosed HIV-1 patients between 2009 and 2017. We genotyped pol genes and performed phylogenetic analyses to identify clusters. Risk factors for clustering and LP were investigated with partial proportional odds and logistic regression. Covariates included transmission mode, HIV-1 subtype, age, origin and cluster activity.ResultsWe included 1,040 individuals in the analysis, 59.6% identified with subtype B and 48.4% in a cluster. Risk factors for clustering included Danish origin (odds ratio (OR): 2.95; 95% confidence interval (CI): 2.21-3.96), non-LP (OR: 1.44; 95% CI: 1.12-1.86), and men who have sex with men (MSM). Increasing age and non-B subtype infection decreased risk (OR: 0.69; 95% CI: 0.50-0.94). Risk for late presentation was lower for active clusters (OR: 0.60; 95% CI: 0.44-0.82) and Danish origin (OR: 0.43; 95% CI: 0.27-0.67). Non-Danish MSM had a lower risk than non-Danish heterosexuals (OR: 0.34; 95% CI: 0.21-0.55).ConclusionHIV-1 transmission in Denmark is driven by early diagnosed, young, subtype B infected MSM. These may benefit most from PrEP. Non-Danish heterosexual HIV-1 patients could benefit from improved communication to achieve earlier diagnosis and treatment.

Long-term trends in HIV care entry: over 15 years of clinical experience from Poland.

INTRODUCTION: Delay in HIV diagnosis and consequently late care entry with low CD4 counts remain a major challenge for the control of the HIV/AIDS epidemic. The aim of this study was to analyse the evolution of characteristics of the HIV epidemic in Poland. METHODS: Cross-sectional data were collected for 3972 HIV-infected patients followed up in 14 of 17 Polish HIV treatment centres in the years 2000-2015. Clinical data were analysed and factors associated with late presentation (baseline CD4 count < 350 cells/µL or history of AIDS-defining illness) and advanced HIV disease (baseline CD4 count < 200 cells/µL or history of AIDS) were identified. RESULTS: The majority (57.6%) of patients entered care late, while 35.6% presented with advanced HIV disease. The odds of being linked to care late or with advanced HIV disease increased consistently across age categories, increasing from 2.55 [95% confidence interval (CI) 1.46-4.47] for late presentation and 3.13 (95% CI 1.49-6.58) for advanced disease for the 21-30-year-old category to 5.2 (95% CI 1.94-14.04) and 8.15 (95% CI 2.88-23.01), respectively, for individuals > 60 years of age. Increased risks of late entry and advanced HIV disease were also observed for injecting drug users [adjusted odds ratio (aOR) 1.74 (95% CI 1.16-2.60) and 1.55 (95% CI 1.05-2.30), respectively], with lower aOR associated with the men who have sex with men transmission route [aOR 0.3 (95% CI 0.31-0.59) and 0.39 (95% CI 0.29-0.53), respectively]. The frequencies of cases in which patients were linked to care late and with advanced HIV disease decreased over time from 67.6% (2000) to 53.5% (2015) (P < 0.0001) and from 43.5% (2000) to 28.4% (2015) (P = 0.001), respectively. CONCLUSIONS: Despite improvements over time, most patients diagnosed with HIV infection entered care late, with a third presenting with advanced HIV disease. Late care entry remains common among people who inject drugs and heterosexual groups.

Late Presentation of HIV Infection in the Netherlands: Reasons for Late Diagnoses and Impact on Vocational Functioning.

Late diagnosis of HIV remains a major challenge in the HIV epidemic. In Europe, about 50% of all people living with HIV are diagnosed late after infection has occurred. Insight into the reasons for late diagnoses is necessary to increase the number of early diagnoses and optimize treatment options. This qualitative study explored the experiences of 34 late-presenters through in-depth semi-structured interviews. A variety of reasons for late diagnoses emerged from our data and led to a division into four groups, characterized by two dimensions. Regarding vocational functioning, the consequences of late diagnoses were health-related problems prior to and since diagnosis, and problems concealing the HIV status. Healthcare providers should offer HIV tests to groups at risk, and be alert for clinical HIV indicator conditions. It is recommended to increase awareness of HIV transmission routes, symptoms and tests, and the benefits of early testing and early entry to HIV care.

Rapid emergence of cryptococcal fungemia, Mycobacterium chelonae vertebral osteomyelitis and gastro intestinal stromal tumor in a young HIV late presenter: a case report.

BACKGROUND: Highly active antiretroviral therapy has significantly changed the natural history of HIV infection, leading to a dramatic reduction of HIV-related morbidity and mortality. Late Presenters, Very Late Presenters and AIDS presenters still represent, also in Europe, including Italy, a huge challenge in terms of diagnostic and therapeutic management. CASE PRESENTATION: A 35-year-old male with a history of fever and back pain. HIV test resulted positive with a high HIV Viral Load and a very low T-CD4 number of cells (5 cells/mm3). Imaging investigations revealed multiple vertebral and pulmonary lesions together with abdominal and thoracic lymphadenopathy. Blood cultures were positive for Cryptococcus neoformans and for Staphylococcus haemolyticus. Lymphnode biopsy resulted positive in PCR for Non-Tuberculosis Mycobacteria (Mycobacterium chelonae). A gastric biopsy also revealed a GIST. The patient also had CMV DNA positive. Although we performed antiretroviral therapy and specific-therapies for each disease, he was transferred to intensive care unit where he died due to an Acute Respiratory Distress Syndrome. CONCLUSION: The reported case is unusual due to the relevant number of opportunistic diseases (both infectious and tumoral) emerging not long after the HIV infection had been diagnosed. Late presenters HIV patients and AIDS presenters still represent a challenge, which is often too complex for clinicians to deal with. In spite of proper management, the risk of suboptimal results cannot be excluded.

Factors associated with the first antiretroviral therapy modification in older HIV-1 positive patients.

BACKGROUND: Rates of first antiretroviral therapy (cART) modifications are high in most observational studies. The age-related differences in treatment duration and characteristics of first cART modifications remain underinvestigated. With increasing proportion of older patients in HIV population it is important to better understand age-related treatment effects. METHODS: Patients were included into this analysis, if being cART naïve at the first visit at the clinic. Follow-up time was measured from the first visit date until first cART modification or 28 February 2013. First cART modification was defined as any change in the third drug component i.e. protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), integrase inhibitor or fusion inhibitor. Cox proportional hazard models were used to identify factors related to first cART modification in three age groups: <30, 30-50 and >50. RESULTS: In total 2027 patients with 14,965 person-years of follow-up (PYFU) were included. The oldest group included 136 patients with 1901, middle group 1202 with 8416 PYFU and youngest group consisted of 689 patients with 4648 PYFU. Median follow-up time was 5.8 (IQR 3.4-9.4) years, median time on first cART was 4.4 (IQR 2.1-8.5) years. 72.4 % of patients started PI-based and 26.1 % NNRTI-based regimen. In total 1268 (62.5 %) patients had cART modification (non-adherence 30.8 %, toxicity 29.6 %). Durability of first cART was the best in patients over 50 y.o. (log-rank test, p = 0.001). Factors associated with discontinuation in this group were late presentation (HR 0.45, [95 % CI 0.23-0.90], p = 0.02) and PI use (HR 2.17, [95 % CI 1.18-4.0], p = 0.01). CONCLUSIONS: Rates of first cART modifications or discontinuation were comparable in all groups; however older patients were significantly longer on first cART regimen.

Has COVID-19 Changed the Incidence and Profile of Late Presenters for HIV Infection in Lodz, Polish Reference Centre, Poland?

Objectives: The aim of this study was to compare the prevalence and characteristics of HIV late presenters (LPs) and advanced LPs (aLPs) registered in the Lodz HIV centre during the COVID-19 pandemic (2020-2021) with those of the pre-pandemic period (2017-2019). Methods: A retrospective analysis was performed of the predictive factors associated with HIV LPs and aLPs based on multivariable logistic regression. The patient entry into specialist HIV care after diagnosis during the pandemic was analysed. Results: Of 121 newly diagnosed HIV infections during the pandemic, 49.6% had late presentation and 36.4% had advanced HIV disease (AHD). In the pre-pandemic period, out of 154 newly diagnosed patients, 58.4% were LPs and 38.3% were aLPs. Independent risk factors for HIV late presentation were older age (OR: 1.04, 95% CI: 1.01-1.076; p = 0.008), diagnosis in hospital (OR: 5.63, 95% CI: 2.87-11.05; p < 0.001) and negative VDRL as compared to positive VDRL (OR: 2.48, 95% CI: 1.19-5.15; p = 0.015). The same predictive factors were associated with aLPs: older age (OR: 1.07, 95% Cl 1.04-1.11; p < 0.001), HIV diagnosis in hospital (OR: 4.25, 95% CI 2.17-8.29; p < 0.001) and negative VDRL as compared to positive VDRL (OR: 4.95, 95% CI 1.87-13.10; p = 0.001). HIV diagnosis during the pandemic was not a risk factor for late presentation nor for advanced late presentation. However, the time between HIV diagnosis and the first visit to an HIV centre was statistically lower in the pre-pandemic period (p = 0.0048); the median lengths of time between the date of HIV testing, the first visit to the centre and the initiation of ART did not differ between these two periods in LPs and aLPs (p > 0.05). Conclusions: The COVID-19 pandemic did not change the prevalence or characteristics of late presentation and aLPs among newly diagnosed patients, nor did it extend the time to enrolment in HIV care or ART introduction in these groups.

The impact of large core and late treatment trials: An update on the modelled annual thrombectomy eligibility of UK stroke patients.

INTRODUCTION: To support decisions about thrombectomy provision, we have previously estimated the annual UK population eligible for treatment as ∼10% of stroke admissions. Since then, eight further randomised trials that could alter the eligibility rate have reported in 2021-23. We updated our estimates of the eligible population from these trials and other recent studies. PATIENTS AND METHODS: An updated decision tree describing the EVT eligible population for UK stroke admissions was produced. Decision criteria were derived from the highest level of evidence available. For nodes where no specific RCT data existed, evidence was obtained from the latest systematic review(s) or the highest quality observational data. RESULTS: We estimate that 15,420 (approximately 15%) of admitted UK stroke patients are now eligible for thrombectomy, or 14,930 if advanced brain imaging using MRI/CT perfusion or collateral assessment were used in all patients. This is a 54% increase in our previous estimate in 2021. Over 50% of LAO strokes are now potentially eligible for thrombectomy. The increase in eligibility is principally due to a much larger cohort of later presenting and/or larger ischaemic core patients. CONCLUSION: Most previously independent LAO stroke patients presenting within 24 h, even in the presence of a large ischaemic core on initial non-contrast CT, should be considered for thrombectomy with use of advanced brain imaging in those presenting beyond 12 h to identify salvageable penumbral brain tissue. Treatment in most patients remains critically time-dependent and our estimates should be interpreted with this in mind.

Persistent poor clinical outcomes of people living with HIV presenting with AIDS and late HIV diagnosis - results from the ICONA cohort in Italy, 2009-2022.

OBJECTIVES: Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD). METHODS: All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm3 without AIDS (non-LD), (ii) pre-ART CD4 count <350/mm3 without AIDS (LD asymptomatic), and (iii) with AIDS events pre-ART (LD-AIDS). The estimated probability and independent risk for mortality (all-cause and cause-specific) and treatment failure were evaluated. RESULTS: Of 6813 participants (2448 non-LD, 3198 LD asymptomatic, and 1167 LD-AIDS), 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD than non-LD (P <0.001) and within the former, for LD-AIDS over LD asymptomatic (P <0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD adjusted hazard ratio (aHR) 5.51, P <0.001) and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR = 4.42, P <0.001), AIDS-related (adjusted subhazard ratio [aSHR] = 16.86, P <0.001), and non-AIDS-related mortality (aSHR = 1.74, P = 0.022) than the rest of the late presenters. Among the short-term survivors in the LD-AIDS group, the long-term mortality was mediated by the lack of immune recovery at 2 years. Finally, LD compared with non-LD and, particularly, among the former, LD-AIDS over LD asymptomatic showed a greater risk of treatment failure. CONCLUSIONS: In recent years, LD subjects, particularly, AIDS presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap.

Characterization and outcomes of difficult-to-treat patients starting modern first-line ART regimens: Data from the ICONA cohort.

OBJECTIVES: Treatment failures to modern antiretroviral therapy (ART) raise concerns, as they could reduce future options. Evaluations of occurrence of multiple failures to modern ART are missing and their significance in the long run is unclear. METHODS: People with HIV (PWH) in the ICONA cohort who started a modern first-line ART were defined as 'difficult to treat' (DTT) if they experienced ≥1 among: i) ≥2 VF (2 viral loads, VL>200 copies/mL or 1 VL>1000 copies/mL) with or without ART change; ii) ≥2 treatment discontinuations (TD) due to toxicity/intolerance/failure; iii) ≥1 VF followed by ART change plus ≥1 TD due to toxicity/intolerance/failure. A subgroup of the DTT participants were matched to PWH that, after the same time, were non-DTT. Treatment response, analysing VF, TD, treatment failure, AIDS/death, and SNAE (Serious non-AIDS event)/death, were compared. Survival analysis by KM curves and Cox regression models were employed. RESULTS: Among 8061 PWH, 320 (4%) became DTT. Estimates of becoming DTT was 6.5% (95% CI: 5.8-7.4%) by 6 years. DTT PWH were significantly older, with a higher prevalence of AIDS and lower CD4+ at nadir than the non-DTT. In the prospective analysis, DTT demonstrated a higher unadjusted risk for all the outcomes. Once controlled for confounders, significant associations were confirmed for VF (aHR 2.23, 1.33-3.73), treatment failure (aHR 1.70, 1.03-2.78), and SNAE/death (aHR 2.79, 1.18-6.61). CONCLUSION: A total of 6.5% of PWH satisfied our definition of DTT by 6 years from ART starting. This appears to be a more fragile group who may have higher risk of failure.

Late presentations and missed opportunities among newly diagnosed HIV patients presenting to a specialty clinic in Lebanon.

Late presentation to medical care of individuals infected with the human immunodeficiency virus (HIV) is linked to poor outcomes and increased morbidity and mortality. Missed opportunities for a prompt diagnosis are frequently reported among late presenters. We aimed to estimate the proportion of late presenters and missed opportunities in diagnosis among newly diagnosed HIV-positive subjects presenting to a specialty clinic in Lebanon. This is a retrospective chart review of all newly diagnosed adult HIV-positive subjects presenting to clinic from 2012 to 2022. Demographic, laboratory, and clinical data were collected at initial HIV diagnosis or presentation to medical care. We defined late presentation as having a CD4 count < 350 or AIDS-defining event regardless of CD4 count. Advanced disease is defined as having a CD4 count below 200 cells/µL or the presence of an AIDS-defining illness, regardless of the CD4 count. A missed opportunity was defined as the presence of an indicator condition (IC) that suggests infection with HIV/AIDS during 3 years preceding the actual HIV diagnosis and not followed by a recommendation for HIV testing. The proportions for demographic, epidemiological, and clinical characteristics are calculated by excluding cases with missing information from the denominator. Our cohort included 150 subjects (92.7% males; 63.6% men who have sex with men (MSM); 33.3% heterosexuals; median age 30.5 years at diagnosis). 77 (51.3%) were late presenters and 53 (35.3% of all subjects, 68.8% of late presenters) had advanced HIV on presentation. Up to 76.5% of late presenters had a presentation with an HIV-related condition at a healthcare provider without getting HIV test within the previous 3 years. The most frequent ICs were weight loss, generalized lymphadenopathy, constitutional symptoms, and chronic idiopathic diarrhea. Overall mortality rate was 4% (6/150 individuals). All-cause mortality among those who presented with AIDS was 15.4% (6/39 subjects). In our setting, late presentations and missed opportunities for HIV diagnosis are common. In the Middle East, AIDS mortality remains high with a large gap in HIV testing. To effectively influence policies, comprehensive analyses should focus on estimating the preventable health and financial burdens of late HIV presentations. Another concern pertains to healthcare providers' attitudes and competencies.

The Role of Late Presenters in HIV-1 Transmission Clusters in Europe.

BACKGROUND: Investigating the role of late presenters (LPs) in HIV-1 transmission is important, as they can contribute to the onward spread of HIV-1 virus before diagnosis, when they are not aware of their HIV status. OBJECTIVE: To characterize individuals living with HIV-1 followed up in Europe infected with subtypes A, B, and G and to compare transmission clusters (TC) in LP vs. non-late presenter (NLP) populations. METHODS: Information from a convenience sample of 2679 individuals living with HIV-1 was collected from the EuResist Integrated Database between 2008 and 2019. Maximum likelihood (ML) phylogenies were constructed using FastTree. Transmission clusters were identified using Cluster Picker. Statistical analyses were performed using R. RESULTS: 2437 (91.0%) sequences were from subtype B, 168 (6.3%) from subtype A, and 74 (2.8%) from subtype G. The median age was 39 y/o (IQR: 31.0-47.0) and 85.2% of individuals were males. The main transmission route was via homosexual (MSM) contact (60.1%) and 85.0% originated from Western Europe. In total, 54.7% of individuals were classified as LPs and 41.7% of individuals were inside TCs. In subtype A, individuals in TCs were more frequently males and natives with a recent infection. For subtype B, individuals in TCs were more frequently individuals with MSM transmission route and with a recent infection. For subtype G, individuals in TCs were those with a recent infection. When analyzing cluster size, we found that LPs more frequently belonged to small clusters (<8 individuals), particularly dual clusters (2 individuals). CONCLUSION: LP individuals are more present either outside or in small clusters, indicating a limited role of late presentation to HIV-1 transmission.

Dialysis education and options for late presenters-An ongoing dilemma.

Pre-dialysis education forms a crucial part of dialysis preparation. Acute start dialysis patients often commence and remain on in-center hemodialysis (ICHD) without the benefit of an informed decision making process for kidney replacement therapy options. The aim of this review is to evaluate the evidence surrounding methods of education provision to the acute dialysis start population and their associated outcomes. Publications have described a holistic education pathway with multimedia provision of information and interactive experiences. One or more trained specialist nurses provided information over 3-5 sessions. Formal education was mostly initiated as an inpatient. 86%-100% of acute start dialysis patients are initiated and remain on ICHD. Following formal education, 21%-58% of patients chose peritoneal dialysis (PD), 10%-24% home hemodialysis, 33%-58% ICHD. This brings the number of patients maintained on an independent form of dialysis similar to the planned dialysis start population. Patients commenced on PD without needing temporary hemodialysis, hence avoided complications associated with such. Patients aged under 75 (p < 0.0001) and males (p = 0.006) were more likely to be influenced by education to select PD. The adjusted 5 year survival rates among discharged patients were similar between home and ICHD groups (73% vs. 71% respectively), with a comparable age of death. A targeted education program in the acute dialysis start population has proven to be feasible. Adaptations are likely required for each center; however, various methods have been shown to be effective, with an increased number of patients choosing an independent dialysis modality when given the choice.

Comparison of Demographic, Clinical, and Echocardiographic Features Between Complete and Incomplete, and Early and Late Presenters of Kawasaki Disease: A 10-Year Single-Center Experience.

INTRODUCTION:  The diagnosis of Kawasaki disease (KD) is based mainly on clinical findings and supported by laboratory tests. Complete KD fulfills the main clinical criteria, while incomplete KD includes patients with fewer main criteria and compatible laboratory or echocardiographic findings. The study compares the demographic, clinical, laboratory, and echocardiographic parameters between the complete and incomplete KD and early and late presenters. Moreover, it describes the coronary manifestations of the study population. METHODOLOGY: A retrospective review of all patients admitted with a diagnosis of KD during the period from January 2010 to September 2020 was conducted. Clinical presentation, laboratory features, echocardiographic observations, and follow-up data were examined. Moreover, the patients were further classified as early presenters (presented within 10 days of fever onset) and late presenters (presented after 10 days of disease onset). A comparison between complete and incomplete KD and early and late presenters was performed for demographic, clinical, and echocardiographic features. RESULTS: A total of 76 patients were admitted with a diagnosis of KD. The median age of presentation was 28 months, with a range of five to 144 months, and the median timing was seven days, with a range of one to 30 days. The median follow-up period was six weeks, with a range of one to 192 weeks. Complete KD was present in 38 patients (50%), and 38 (50%) had incomplete KD. Skin manifestations, oral mucosal changes, skin desquamation, conjunctivitis, and lymphadenopathy were present more in patients with complete KD than incomplete ones. Complete and incomplete diseases did not differ regarding coronary artery lesions. Of the patients, 53 (70%) presented 10 days or less after the onset of fever, and 23 (30%) presented after the 10th day of disease onset. Comparison between early and late presenters revealed significantly greater mucus membrane changes and lymphadenopathy manifestations among the early presenters and coronary artery lesions among the late presenters. CONCLUSION: The clinical features of KD should prompt early referral for evaluation, echocardiography, and early administration of intravenous immunoglobulin to prevent coronary artery complications. The complete form of Kawasaki does not have more frequent coronary artery lesions than the incomplete form. Additionally, late presenters may be at increased risk for coronary artery abnormalities than early presenters.

Trends of Transmitted and Acquired Drug Resistance in Europe From 1981 to 2019: A Comparison Between the Populations of Late Presenters and Non-late Presenters.

Background: The increased use of antiretroviral therapy (ART) has decreased mortality and morbidity of HIV-1 infected people but increasing levels of HIV drug resistance threatens the success of ART regimens. Conversely, late presentation can impact treatment outcomes, health costs, and potential transmission of HIV. Objective: To describe the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in HIV-1 infected patients followed in Europe, to compare its patterns in late presenters (LP) vs non-late presenters (NLP), and to analyze the most prevalent drug resistance mutations among HIV-1 subtypes. Methods: Our study included clinical, socio-demographic, and genotypic information from 26,973 HIV-1 infected patients from the EuResist Integrated Database (EIDB) between 1981 and 2019. Results: Among the 26,973 HIV-1 infected patients in the analysis, 11,581 (42.9%) were ART-naïve patients and 15,392 (57.1%) were ART-experienced. The median age was 37 (IQR: 27.0-45.0) years old and 72.6% were males. The main transmission route was through heterosexual contact (34.9%) and 81.7% of patients originated from Western Europe. 71.9% of patients were infected by subtype B and 54.8% of patients were classified as LP. The overall prevalence of TDR was 12.8% and presented an overall decreasing trend (p for trend < 0.001), the ADR prevalence was 68.5% also with a decreasing trend (p for trend < 0.001). For LP and NLP, the TDR prevalence was 12.3 and 12.6%, respectively, while for ADR, 69.9 and 68.2%, respectively. The most prevalent TDR drug resistance mutations, in both LP and NLP, were K103N/S, T215rev, T215FY, M184I/V, M41I/L, M46I/L, and L90M. Conclusion: Our study showed that the overall TDR (12.8%) and ADR (68.5%) presented decreasing trends during the study time period. For LP, the overall TDR was slightly lower than for NLP (12.3 vs 12.6%, respectively); while this pattern was opposite for ADR (LP slightly higher than NLP). We suggest that these differences, in the case of TDR, can be related to the dynamics of fixation of drug resistance mutations; and in the case of ADR with the more frequent therapeutic failure in LPs.

Prevalence of Late Presenters and Advanced HIV Disease in HIV Patients and Their Related Factors in Iran: Results from 19 Years of National Surveillance HIV Data.

Late presenters (LP) and Advanced HIV Disease (AHD) represent important missed opportunities to reduce secondary transmission and undesirable HIV outcomes. Despite efforts, the diagnoses are still delayed for the majority of patients. This cross-sectional study was conducted using the Iranian national HIV surveillance database from 2001 to 2019, to determine the factors affecting AHD and LP in Iran. To determine LP (CD4 ≤ 350 cells/µL) and AHD (CD4 ≤ 200 cells/µL), the first patients' CD4 at baseline were used. To examine the relationship between the covariates and LP or AHD, a Logistic Regression was applied. The adjusted odds ratio (AOR) stated to report the relationship. Totally, 13,571 patients were included in the study. Of these, 4,060 (29.92%) were AHD and 7,161 (52.77%) LP. Female gender [AOR = 0.88, 95% confidence interval (CI): 0.80-0.97], higher education (AOR = 0.80, 95% CI: 0.69-0.93), and having a positive HIV spouse (AOR = 0.75, 95% CI = 0.66-0.85) significantly decreased odds of LP (p < .05). However, older age (AOR = 2.53, 95% CI: 2.20-2.91) was a risk factor for LP. For AHD, years of detection (AOR = 1.16, 95% CI: 1.06-1.27), older age (AOR = 2.49, 95% CI: 2.12-2.92), and having a spouse with high-risk behavior (AOR = 1.23, 95% CI: 1.02-1.49) led to higher odds. (p < .05). Also, female (AOR = 0.82, 95% CI: 0.73-0.92) and having a positive HIV spouse (AOR = 0.67, 95% CI: 0.58-0.78) were protective factors for ADH. The present study estimated that approximately two-thirds of HIV patients are LP and one-third are AHD in Iran. Older age, male gender, lower education, and having a spouse with high-risk behavior were the factors affecting LP and AHD. Thus, to reduce the percentage of patients with LP and AHD in Iran, improvements in knowledge and periodic screening programs are necessary for these groups.

Advanced HIV Infection in Treatment-Naïve Individuals: Effectiveness and Persistence of Recommended 3-Drug Regimens.

BACKGROUND: Approximately 20% of newly diagnosed people with HIV (PWH) in the United States have advanced HIV infection, yet the literature on current antiretroviral therapy (ART) options is limited. The discontinuation/modification and effectiveness of common regimens were compared among ART-naïve people with advanced HIV infection (CD4 cell count <200 cells/µL). METHODS: ART-naïve adults with advanced HIV infection initiating bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or a boosted darunavir (bDRV)-, dolutegravir (DTG)-, or elvitegravir/cobicistat (EVG/c)-based 3-drug regimen between January 1, 2018, and July 31, 2019, in the OPERA cohort were included. The association between regimen and discontinuation or viral suppression (<50 or <200 copies/mL) was assessed using Cox proportional hazards models with inverse probability of treatment weights. RESULTS: Overall, 961 PWH were included (416 B/F/TAF, 106 bDRV, 271 DTG, 168 EVG/c); 70% achieved a CD4 cell count ≥200 cells/µL over a 16-month median follow-up. All regimens were associated with a statistically higher likelihood of discontinuation than B/F/TAF (bDRV: adjusted hazard ratio [aHR], 2.65; 95% CI, 1.75-4.02; DTG: aHR, 2.42; 95% CI, 1.75-3.35; EVG/c: aHR, 3.52; 95% CI, 2.44-5.07). Compared with B/F/TAF, bDRV initiators were statistically less likely to suppress to <50 copies/mL (aHR, 0.72; 95% CI, 0.52-0.99) and <200 copies/mL (aHR, 0.55; 95% CI, 0.43-0.70); no statistically significant difference was detected with DTG or EVG/c. CONCLUSIONS: Among people with advanced HIV infection, those initiating B/F/TAF were less likely to discontinue/modify their regimen than those on any other regimen, and more likely to achieve viral suppression compared with those on bDRV but not compared with those on other integrase inhibitors.

The serious threat of late presenters HIV-infected patients in the context of the COVID-19 pandemic.

The impact of current SARS-CoV-2 pandemic on the healthcare services had serious consequences, especially for the most fragile populations such as HIV-positive subjects. In the period April to September 2020 we reported four cases of HIV-infected late presenters with an AIDS-defining life-threatening condition that, due to the difficult access to the hospital during the pandemic, were characterized by a delayed HIV recognition and institution of correct treatment. Even after two decades of highly active antiretroviral therapy late presenters HIV-infected patients still represent a serious clinical challenge.

Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study.

Background: Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. Methods: From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005-2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4<500 cells/µL). We used logistic regression and propensity score matching. Findings: We included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP (1145 non-LP with two-year CD4 count >500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200-500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]).Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Interpretation: Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Funding: Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.

Lymphoid interstitial pneumonitis in a newly diagnosed late presenter of human immunodeficiency virus infection: a case report.

BACKGROUND: An increase has been described throughout the years in the frequency of various uncommon diseases in people living with human immunodeficiency virus (HIV). Particularly late presenters are associated with a significant risk not only for acquired immune deficiency syndrome (AIDS)-defining conditions but also for non AIDS-defining diseases which aggravate the prognosis of patients. Lymphoid interstitial pneumonitis (LIP) is one of these conditions described more often after the onset of HIV epidemic. LIP is a benign polyclonal lymphoproliferative disorder of the lung with not well characterized clinical and radiographic findings. CASE PRESENTATION: We report the diagnostic approach and clinical progress of a newly diagnosed late presenter of HIV infection with respiratory problems in our HIV unit. The findings of computed tomography indicated the diagnosis of HIV-associated LIP, although this condition is mainly described in a normal range of CD4 cell count. CONCLUSION: This case presentation highlights the importance of timely diagnosis and initiation of antiretroviral therapy. The increase of CD4 cell count and viral suppression may improve the symptoms of LIP.

The cost-effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa.

INTRODUCTION: Many HIV-positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced-prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3 . We investigated the cost-effectiveness of this enhanced-prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. METHODS: The REALITY trial enrolled from June 2013 to April 2015. A decision-analytic model was developed to estimate the cost-effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard-prophylaxis, enhanced-prophylaxis, standard-prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced-prophylaxis (CrAg-positive) or standard-prophylaxis (CrAg-negative), the second to enhanced-prophylaxis (CrAg-positive) or enhanced-prophylaxis without fluconazole (CrAg-negative) and the third to standard-prophylaxis with fluconazole (CrAg-positive) or without fluconazole (CrAg-negative). The model estimated costs, life-years and quality-adjusted life-years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. RESULTS: Enhanced-prophylaxis was cost-effective at cost-effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost-effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced-prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced-prophylaxis components. Enhanced-prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced-prophylaxis still conveyed health gains in CrAg-negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost-effective unless the price of CrAg testing fell below US$2.30. CONCLUSIONS: The REALITY enhanced-prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost-effective. Efforts should continue to ensure that components are accessed at lowest available prices.