AIDS-defining Events Research Articles

Risk of tuberculosis after achieving HIV virological suppression on antiretroviral therapy: a Danish nationwide prospective cohort study.

In countries with low tuberculosis (TB) burden, the risk of TB in people with HIV (PWH) once HIV virological suppression is achieved is not fully understood. In a nationwide cohort, we included all adult PWH from the Danish HIV Cohort initiating antiretroviral therapy (ART) (1995-2017) without prior TB disease. We used Kaplan-Meier estimation and Poisson regression to calculate TB incidence rate (IR) after six months of ART, along with associated risk factors and mortality rates (MR). Among 6,849 PWH initiating ART (median follow-up 7.4 years), 84 developed TB (IR 1.4/1000 person-year [PY]), 54 of them beyond six months of ART initiation, IR 0.97/1000 PY (95%CI:1.17-1.79): 1.95 (95%CI:1.34-2.76) in non-Danish born, 0.36 (95%CI:0.21-0.62) in Danish-born without injection drug use (IDU), and 2.95 (95%CI:1.53-5.66) in Danish-born with IDU. Danish-born with suppressed viremia, and no IDU or known TB exposures had the lowest risk (IR 0.05/1000 PY).In the adjusted analysis, being non-Danish born (aIRR 4.27[95%CI:2.36-7.72]), IDU (aIRR 4.95[95%CI:2.55-9.62]), and previous AIDS-defining events (aIRR 2.05[95%CI:1.06-3.94]) raised TB risk, while suppressed HIV-RNA (aIRR 0.58[95%CI:0.34-0.99]) reduced it. The overall MR for HIV/TB co-infected post- ART was high, at 48.9/1000 PY (95%CI:30.4-78.7). The TB risk remains elevated in PWH beyond six months of ART initiation, especially among migrants, IDU, those without suppressed HIV-RNA, and individuals exposed to high TB endemic areas or with social risk determinants of health. Conversely, PWH without these risk factors have a TB risk similar to the general population and would not require targeted TB screening strategies.

The association between HIV-related stigma, HIV knowledge and HIV late presenters among people living with HIV (PLHIV) attending public primary care clinic settings in Selangor.

HIV late presenters were defined as individuals presenting with a CD4 count below 350 cells/μL or with an AIDS-defining event, according to the European Late Presenter Consensus working group. Early diagnosis and treatment of HIV have proven beneficial for people living with HIV (PLHIV), reducing the burden on healthcare systems, and contributing to ending the HIV/AIDS epidemic. However, in Malaysia, over 50% of newly diagnosed HIV patients present late, leading to increased morbidity and premature mortality. This study aims to determine the prevalence of late HIV presenters and its association with HIV-related stigma and HIV knowledge among PLHIV attending public primary care clinics in Selangor. A cross-sectional study was conducted at selected public health clinics in Selangor, involving PLHIV aged 18 years and older, who were diagnosed since 2019. HIV-related stigma was measured using the Malay version of Berger's HIV Stigma Scale, and HIV knowledge was assessed using the Malay version of Brief HIV-KQ-18. Univariate and multivariate logistic regression analyses were performed to identify factors associated with late HIV presentation. A total of 400 participants were included in the study, with 60.0% (n = 240, 95% CI: 55.0-65.0) classified as late presenters. The participants had a mean age of 30.29 (±7.77) years. The risk factors for late presenters were high levels of HIV-related stigma (aOR = 1.049, 95% CI: 1.034-1.063, p-value <0.001), low levels of HIV knowledge (aOR = 0.709, 95% CI: 0.646-0.778, p-value <0.001), tertiary education background (aOR = 15.962, 95% CI: 1.898-134.235, p-value = 0.011), and being single (aOR = 3.582, 95% CI: 1.393-9.208, p-value = 0.008). This study highlights the association between high levels of HIV-related stigma, low levels of HIV knowledge, and late HIV presentation. Interventions targeting stigma reduction and HIV education can promote early testing and prompt access to care, improving health outcomes for PLHIV.

Long-term safety and impact of immune recovery in heavily treatment-experienced adults receiving fostemsavir for up to 5 years in the phase 3 BRIGHTE study.

Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes. The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021). Safety endpoints were assessed in participants who received fostemsavir + optimized background therapy. In participants with baseline CD4+ T-cell count <200 cells/mm3, exposure-adjusted adverse event (AE) rates were assessed among subgroups with or without CD4+ T-cell count ≥200 cells/mm3 at any time during 48-week analysis periods through week 192. Through a median of 258 weeks (range, 0.14-319) of treatment, discontinuations due to AEs occurred in 30/371 (8%) participants. Serious AEs were reported in 177/371 (48%) participants, including 16 drug-related events in 13 (4%) participants. Thirty-five (9%) deaths occurred, primarily related to AIDS or acute infections. COVID-19-related events occurred in 25 (7%) participants; all resolved without sequelae. Among participants with baseline CD4+ T-cell count <200 cells/mm3, 122/162 (75%) achieved CD4+ T-cell count ≥200 cells/mm3 at week 192. Exposure-adjusted AE rates were markedly lower among participants achieving CD4+ T-cell count ≥200 cells/mm3 at any time vs those sustaining <200 cells/mm3. No new AIDS-defining events were reported after week 48 in participants with CD4+ T-cell count ≥200 cells/mm3. Cumulative safety findings through the BRIGHTE 240-week interim analysis are consistent with other trials in HTE participants with advanced HIV-1 and comorbid disease. Reduced rates of AIDS-defining events and AEs were observed in participants with immunologic recovery on fostemsavir-based treatment. NCT02362503, https://clinicaltrials.gov/study/NCT02362503.

Characteristics and outcomes of people living with HIV hospitalised at tertiary healthcare institutions during the COVID-19 pandemic in Mexico City

BackgroundWhile existing research on people living with HIV (PWH) during the COVID-19 pandemic primarily focused on their clinical outcomes, a critical gap remains in understanding the implications of COVID-19 delivery of in-hospital care services to PWH. Our study aimed to describe the characteristics and outcomes of PWH hospitalised during 2020 in Mexico City, comparing patients admitted due to COVID-19 vs. patients admitted due to other causes.MethodsAll PWH hospitalised for ≥ 24 h at four institutions in Mexico City from January 1st to December 31st, 2020 were included. Patients were classified into two groups according to the leading cause of their first hospitalisation: COVID-19 or non-COVID-19. Characteristics among groups were compared using chi-square and Kruskal tests. A Cox model was used to describe the risk of death after hospitalisation and the characteristics associated with this outcome. Mortality and hospitalisation events were compared to data from 2019.ResultsOverall, we included 238 PWH hospitalised in 2020. Among them, 42 (18%) were hospitalised due to COVID-19 and 196 (82%) due to non-COVID-19 causes, mainly AIDS-defining events (ADE). PWH hospitalised due to COVID-19 had higher CD4 + cell counts (380 cells/mm3 [IQR: 184–580] vs. 97 cells/mm3 [IQR: 34–272], p < 0.01) and a higher proportion of virologic suppression (VS) compared to those hospitalised due to non-COVID-19 causes (92% vs. 55%, p < 0.01). The adjusted hazard ratio (aHR) for AIDS was 3.1 (95%CI: 1.3–7.2). COVID-19 was not associated with death (aHR 0.9 [95%CI: 0.3–2.9]). Compared to 2019, mortality was significantly higher in 2020 (19% vs. 9%, p < 0.01), while hospitalisations decreased by 57%.ConclusionsPWH with COVID-19 had higher VS and CD4 + cell counts and lower mortality compared to those hospitalised due to non-COVID-19-related causes, who more often were recently diagnosed with HIV and had ADEs. Most hospitalisations and deaths in 2020 in PWH were related to advanced HIV disease. The increased mortality and decreased hospitalisations of PWH during 2020 evidence the impact of the interruption of health services delivery for PWH with advanced disease due to the pandemic. Our findings highlight the challenges faced by PWH during 2020 in a country where advanced HIV remains a concern.

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.

Risk Factors for Late HIV Presentation in Patients Treated at a Single Belgian Reference Centre from 2018 to 2022.

A late HIV diagnosis is associated with increased mortality and morbidity, increased healthcare costs and increased onward viral transmission. In this regard, we retrospectively analysed the characteristics of patients who presented for care at our centre from January 2018 to December 2022 to assess the proportion of patients and factors associated with late HIV presentation. We collected data from the Liège University Hospital database, and we used binary logistic regression models to analyse the impact of individuals' characteristics on late presentation. Among 167 participants, 38.3% were late presenters (LPs) (presenting for care with a CD4+ T-cell count < 350 cells/mm3 or after an AIDS-defining event), and 21.6% were late presenters with advanced disease (LPs-AD) (presenting for care with a CD4+ T-cell count < 200 cells/mm3 or after an AIDS-defining event). The risk of being an LPs-AD was increased in older individuals (OR on log-transformed age: 7.5) and individuals of sub-Saharan African origin compared to individuals of Belgian or other origin (ORs of 0.30 and 0.25, respectively). The results of this study suggest that broadening the focus beyond the previously common risk groups is essential to prevent late diagnosis.

Clinical outcomes and risk factors for immune recovery and all-cause mortality in Latin Americans living with HIV with virological success: a retrospective cohort study.

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. 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. 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. 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.

AIDS-defining events among people living with HIV who have been under continuous antiretroviral therapy for more than one year, a German cohort study 1999-2018.

This study examined the characteristics, incidence and prognostic factors of the first AIDS-defining condition developed after more than one year of continuous antiretroviral therapy (ART) among people living with HIV (PLHIV). We used data from two multicentre observational cohorts of PLHIV in Germany between 1999 and 2018. Our outcome was the first AIDS-defining event that occurred during follow-up after more than one year of continuous ART. Descriptive analyses at ART initiation, at the time of the AIDS event and of the most frequently observed types of AIDS-defining illnesses were performed. We calculated the incidence rate (IR) per 1000 person-years (PY) and used a bootstrap stepwise selection procedure to identify predictors of the outcome. A total of 12,466 PLHIV were included in the analyses. 378 developed the outcome, constituting an overall IR of 5.6 (95% CI 5.1-6.2) AIDS events per 1000 PY. The majority of PLHIV was virally suppressed at the time of the event. Oesophageal candidiasis and wasting syndrome were the most frequently diagnosed AIDS-defining illnesses. We found a low CD4 count at ART initiation, a previous AIDS-defining condition and transmission through intravenous drug use to be meaningful prognostic factors of the outcome. The overall rate of AIDS-defining events among PLHIV under long-term ART was low, highlighting the importance of continuous treatment. PLHIV who started ART with indicators of impaired immune functioning were more susceptible to disease progression, suggesting that the public health response should continue to focus on early and sustained treatment for all PLHIV.

Torque Teno Virus load is associated with CDC stage and CD4+ cell count in people living with HIV but unrelated to AIDS-defining events and Human Pegivirus load.

Torque Teno Virus (TTV) is a non-enveloped, circular single-strand DNA virus and part of the human virome. The replication of TTV was related to the immune status in patients treated with immunosuppressive drugs after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH). In this analysis serum samples of PLWH from the RESINA multicenter cohort were reanalysed for TTV. Investigated clinical and epidemiological parameters included Pegivirus (HPgV) load, age, sex, HIV load, CD4+ cell count (CDC 1, 2, 3) and CDC clinical stages (1993 CDC classification system, A, B, C) before initiation of antiretroviral treatment. Regression analysis was used to detect possible associations among parameters. Our analysis confirmed TTV as a strong predictor of CD4+ cell count and CDC class 3. This relationship was used to propose a first classification of TTV load in regard to clinical stage. We found no association with clinical CDC stages A, B and C. HPgV load was inversely correlated with HIV load but not TTV load. TTV load was associated with immunodeficiency in PLWH. Neither TTV- nor HIV load were predictive for the clinical categories of HIV infection.

Trends and the associated factors of optimal immunological response and virological response in late anti-retroviral therapy initiation HIV cases in Taiwan from 2009 to 2020

BackgroundLate cART initiation (CD4 count ≤200 cells/μL or AIDS-defining opportunistic illnesses [AOIs] at cART initiation) impedes CD4 count recovery and virologic suppression after cART initiation. However, studies to evaluate trends of and modifiable factors for optimal immunological response (IR) and virological response (VR) in people living with HIV (PLWH) with late cART initiation with the current HIV treatment strategies are limited. MethodsWe retrospectively identified 475 PLWH with late cART initiation in 2009–2020. Patients were grouped based on the presence of IR (CD4 count ≥200 cells/μL) or VR (plasma viral load [PVL] ≤ 50 copies/mL) within 18 months after cART initiation (403 [84.8%] IR(+) and 72 [15.2%] IR(−); 422 [88.8%] VR(+) and 53 [11.2%] VR(−)). We used Joinpoint regression to identify IR (+) and VR(+) proportion changes. ResultsFrom 2009 to 2020, the proportion of IR(+) patients remained unchanged (75% to 90%, P = 0.102), whereas that of VR(+) patients increased significantly (75% to 95%, P = 0.007). No join point was identified for either IR(+) or VR(+), and the annual percentage change was 0.56% (nonsignificant) and 1.35% (significant) for IR(+) and VR(+), respectively. Compared to IR(−) patients, IR(+) patients were more likely to have a higher pre-cART PVL, to start with a first-line INSTI-based regimen, or to start cART within 14 days of HIV diagnosis but were less likely to have chronic kidney disease, composite AOIs, or a lower pre-cART CD4 count. Compared to VR(−) patients, VR(+) patients were more likely to start a single-tablet regimen but were less likely to have a higher pre-cART PVL. ConclusionsOur study identified several modifiable factors for optimal IR (rapid cART initiation and INSTI-based regimen initiation) and for optimal VR (STR initiation) among late initiators, which may guide early treatment modifications to reduce their AIDS-defining event incidence and mortality.

Unraveling clinical outcomes of long-term cART treatment in HIV-1 patients with or without the Brazilian GWGR motif in the V3 loop.

The presence of genetic mutations in HIV poses a significant challenge, potentially leading to antiretroviral resistance and hampering therapeutic development. The Brazilian population has presented variations in the HIV envelope V3 loop gene, especially the GWGR motif. This motif has been linked to reduced transmission potential and slower CD4+ T cell decline. This study aimed to assess clinical outcomes in patients with HIV-1 infected with strains containing the GWGR motif compared with those without it during long-term cART. A cohort of 295 patients with HIV was examined for the GWGR motif presence in the V3 loop. A total of 58 samples showed the GWGR signature, while 237 had other signatures. Multifactorial analyses showed no significant differences in demographic characteristics, CD4+ cell count, AIDS progression, or mortality between GWGR carriers and others. However, the mean interval between the first positive HIV test and the initial AIDS-defining event was more than two times longer for women carrying the GWGR signature (p = 0.0231). We emphasize the positive impact of cART on HIV/AIDS treatment, including viral suppression, CD4+ cell preservation, and immune function maintenance. Although no significant differences were found during cART, residual outcomes reflecting adherence challenges were observed between diagnosis and the first AIDS-defining event. The previously described outcomes, highlighting statistically significant differences between individuals carrying the GPGR motif compared with those with the Brazilian GWGR motif, may be directly linked to the natural progression of infection before advancements in cART. Presently, these physicochemical aspects may no longer hold the same relevance.

Incidence of bacterial respiratory infection and pneumonia in people with HIV with and without airflow limitation

ObjectivesWe aimed to determine the incidence rate, pathogen composition, and risk factors, particularly airflow limitation, associated with bacterial respiratory infection and pneumonia in a prospective cohort of well-treated people with HIV (PWH) between 2015-2021. MethodsWe included 1007 PWH from the Copenhagen Comorbidity in HIV infection (COCOMO) study. Spirometry was performed at inclusion. Microbiology samples were collected prospectively. Cumulative incidence was determined by the Aalen-Johansen estimator. Cox proportional hazard models were used to calculate risk factors, adjusted for traditional and HIV-specific variables. ResultsThe incidence rates of first bacterial respiratory infection and pneumonia were 12.4 (95% CI 9.7-15.5) and 5.5 (95% CI: 3.8-7.7) per 1000 person-years, respectively. The cumulative incidence of pneumonia was four times higher in PWH with airflow limitation (11.8% vs 3.2%, P <0.001). Risk factors for bacterial respiratory infection were airflow limitation (hazard ratio [HR] 2.9, [95% CI: 1.7-5.1], P <0.001), smoking (HR 2.3, [95% CI: 1.4-3.8], P <0.001), and previous AIDS-defining event (HR 2.0, [95% CI: 1.2-3.3], P = 0.009). For pneumonia, airflow limitation (HR 2.7, [95% CI: 1.2-6.3], P = 0.016), smoking (HR 2.5, [95% CI: 1.2-5.4], P = 0.016), and older age (HR 1.5, [95% CI: 1.1-2.1], P = 0.015) were identified as risk factors. ConclusionsIncreased emphasis on airflow limitation prevention, including smoking cessation, may reduce the burden of bacterial respiratory infection and pneumonia in PWH.

Rapid ART initiation with bictegravir/emtricitabine/tenofovir alafenamide in individuals presenting with advanced HIV disease (Rainbow study)

BackgroundA rapid ART initiation approach can be beneficial in people with advanced HIV disease, in consideration of their high morbidity and mortality. The aim of our study was to evaluate the feasibility, efficacy and safety of rapid ART start with BIC/FTC/TAF in this setting. MethodsPilot, single-centre, single-arm, prospective, phase IV clinical trial conducted in a tertiary Italian hospital. Thirty ART-naïve people presenting with advanced HIV-1 diagnosis (defined as the presence of an AIDS-defining event and/or CD4 cell count <200 µL), were enrolled. Main exclusion criteria were active tuberculosis, cryptococcosis and pregnant/breastfeeding women. BIC/FTC/TAF was started within 7 days from HIV diagnosis. The primary endpoint was clinical or virologic failure (VF). Immunological parameters, safety, feasibility, neurocognitive performances and patient-reported outcomes were assessed as well. ResultsOver the study period, 40 (34%) of 116 patients diagnosed with HIV infection at INMI Spallanzani had advanced disease, of whom 30 (26%) were enrolled. The proportion of participants with HIV-RNA <50 cp/mL was 9/30 (30%) at week (w) 4, 19/30 (63%) at w12, 24/30 (80%) at w24, 23/30 (77%) at w36 and 27/30 (90%) at w48. Two unconfirmed VF occurred. No ART discontinuation due to toxicity or VF was observed. No ART modification was performed based on the review of genotype and no mutations for the study drugs were detected. Mean CD4 cells count changed by 133 cells/μL at BL to 309 cells/μL at w 48 and 83% of participants had a CD4 > 200 cells/µL at w 48. Two participants developed IRIS and one was diagnosed with disseminated TB and needed an ART switch. InterpretationsOur results support the feasibility, efficacy and safety of BIC/FTC/TAF as a rapid ART strategy in patients with advanced HIV disease.

Late Diagnosis in HIV with New and Old Definitions; Data from a Regional Hospital in Turkey.

Late presentation for HIV care, continues to be a challenge, leading to increased morbidity, mortality, and society costs. The study aimed to determine the rates of late diagnosis (LD) and patient characteristics in Turkey, utilizing the new definition excluding recently infected. The study included patients admitted to the hospital between 1998 and 2023, with at least 1 year of follow-up. Patients without a CD4 count at their initial admission were excluded. Two definitions of presentation were used: LD, (CD4<350 cells/mL or AIDS-defining event) and advanced disease (AD), (CD4<200 cells/mL or AIDS-defining event). Individuals with recent evidence of infection were reclassified as "not late". Out of the 914 patients meeting the criteria and the analysis focused on 794 treatment-naïve patients, with 90.6% being male and an average age of 36.0 ± 12.0 years. Using the previous definition, 48.9% were diagnosed as late, while the new definition identified 47.2%. A total of 183 patients (23%) were diagnosed with AD, and 25.9% of the diagnoses occurred during the COVID-19 Pandemic. The rate of LD increased during the pandemic compared to before (55.8% vs 44.2%, p=0.005), as did the rate of AD (30.1% vs 20.6%, p=0.007). There was no significant relationship between gender and LD. Patients with LD were older (median ages were 31 vs 36 in groups, p<0.001), had poorer virological response, higher mortality rates (4.8% vs 1.2%, p=0.003), and shorter survival compared to those without (log rank=0.004). HIV patients with LD have poorer prognosis with older age as well as disruption of health services during the pandemic as risk factors. To improve outcomes, multicenter studies should investigate missed opportunities and specific risk factors in our region, and we should screen at-risk populations, promote awareness among underdiagnosed populations, and advocate testing even in disastrous situations.

Impact of Hepatitis C cure on risk of mortality and morbidity in people with HIV after ART initiation.

Hepatitis C Virus (HCV) co-infection is associated with increased morbidity and mortality in people with HIV (PWH). Sustained virological response (SVR) decreases the risk of HCV-associated morbidity. We compared mortality, risk of AIDS-defining events, and non-AIDS non-liver (NANL) cancers between HCV co-infected PWH who reached SVR and mono-infected PWH. Adult PWH from 21 cohorts in Europe and North America that collected HCV treatment data were eligible if they were HCV-free at time of ART initiation. Up to 10 mono-infected PWH were matched (on age, sex, date of ART start, HIV acquisition route, and being followed at the time of SVR) to each HCV co-infected PWH who reached SVR. Cox models were used to estimate relative hazards (HR) of all-cause mortality, AIDS-defining events, and NANL cancers after adjustment. Among 62,495 PWH, 2,756 acquired HCV, of whom 649 reached SVR. For 582 of these, ≥1 mono-infected PWH could be matched, producing a total of 5,062 mono-infected PWH. The estimated HRs comparing HCV co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95%CI 0.12-0.73] for mortality, 0.85 [0.42-1.74] for AIDS-defining events, and 1.21 [0.86-1.72] for NANL cancer. PWH who reached SVR a short time after HCV acquisition were not at higher risk of overall mortality compared to mono-infected PWH. However, the apparent higher risk of NANL cancers in HCV co-infected PWH who reached SVR after a DAA-based treatment compared to mono-infected PWH, though compatible with a null association, suggests a need for monitoring of those events following SVR.

AIDS in the era of antiretroviral therapy: Changes in incidence rates and predictors of AIDS among people living with HIV under clinical care in Germany, a cohort study 1999-2018.

This study examined the incidence rates and predictive utility of established prognostic factors forthe progression to AIDS among people living with HIV under clinical care. We used data from two observational cohorts of people living with HIV in Germany between 1999 and 2018. The outcome measure was the first AIDS-defining event that occurred during follow-up. Incidence rates (IRs) per 1000 person-years (PY) were calculated by years of follow-up and calendar periods. We used Cox models in our prediction analyses, including CD4 count, viral load, and age at baseline to estimate the predictive performance. Additionally, we included transmission mode to examine its predictive utility. A total of 23 299 people living with HIV were included in the analyses. Of these, 1832 developed a first AIDS event during follow-up, constituting an overall rate of 14.6/1000 PY (95% confidence interval [CI] 13.9-15.2). IRs were highest in the first year of follow-up (45.6/1000 PY, 95% CI 42.6-48.8) and then declined continuously. IRs were highest among people living with HIV who enrolled between 1999 and 2003 (36.1/1000 PY, 95% CI 32.6-40.0). A low CD4 count, high viral load, and older age at baseline increased the likelihood of progressing to AIDS. Adding transmission mode to the models did not improve the predictive performance. The rates of a first AIDS event among people living with HIV have continuously declined in Germany. Health outcomes depend on a person's CD4 count, viral load, and age but not on transmission mode. To further reduce the number of AIDS cases, the focus should be on groups more likely to present in progressed stages of their HIV infection.

Efficacy of Dolutegravir versus Darunavir in Antiretroviral First-Line Regimens According to Resistance Mutations and Viral Subtype

Dolutegravir (DTG)-based first-line regimens have shown superior efficacy versus darunavir (DRV)-based ones in randomized trials. We compared these two strategies in clinical practice, particularly considering the role of pre-treatment drug resistance mutations (DRMs) and of the HIV-1 subtype. The multicenter Antiretroviral Resistance Cohort Analysis (ARCA) database was queried to identify HIV-1-positive patients starting a first-line therapy with 2NRTIs plus either DTG or DRV between 2013 and 2019. Only adult (≥18 years) patients with a genotypic resistance test (GRT) prior to therapy and with HIV-1 RNA ≥1000 copies/mL were selected. Through multivariable Cox regressions, we compared DTG- versus DRV-based regimens in the time to virological failure (VF) stratifying for pre-treatment DRMs and the viral subtype. A total of 649 patients was enrolled, with 359 (55.3%) and 290 (44.7) starting DRV and DTG, respectively. In 11 months of median follow-up time, there were 41 VFs (8.4 in 100 patient-years follow-up, PYFU) and 15 VFs (5.3 per 100 PYFU) in the DRV and DTG groups, respectively. Compared with a fully active DTG-based regimen, the risk of VF was higher with DRV (aHR 2.33; p = 0.016), and with DTG-based regimens with pre-treatment DRMs to the backbone (aHR 17.27; p = 0.001), after adjusting for age, gender, baseline CD4 count and HIV-RNA, concurrent AIDS-defining event and months since HIV diagnosis. Compared with patients harboring a B viral subtype and treated with a DTG-based regimen, patients on DRV had an increased risk of VF, both in subtype B (aHR 3.35; p = 0.011), C (aHR 8.10; p = 0.005), CRF02-AG (aHR 5.59; p = 0.006) and G (aHR 13.90; p < 0.001); DTG also demonstrated a reduced efficacy in subtypes C (versus B, aHR 10.24; p = 0.035) and CRF01-AE (versus B; aHR 10.65; p = 0.035). Higher baseline HIV-RNA and a longer time since HIV diagnosis also predicted VF. In line with randomized trials, DTG-based first-line regimens showed an overall superior efficacy compared with DRV-based regimens. GRT may still play a role in identifying patients more at risk of VF and in guiding the choice of an antiretroviral backbone.

Real-world data in late presentation of HIV infection in Suzhou, China: Results from four consecutive cross-sectional surveys, 2017-2020.

This study aimed to examine the real prevalence of late presentation of HIV infection and to identify factors associated with late HIV presentation among patients with newly diagnosed HIV/AIDS in Suzhou, China. Patients with newly diagnosed HIV/AIDS who registered in national AIDS surveillance system from 2017 to 2020 were included in this study. Late presentation (LP) of HIV infection was defined as HIV diagnosis with a CD4 count < 350 cells/μL or an AIDS-defining event. Multivariable logistic regression analyses were used to identify factors associated with LP. A total of 2,300 patients were enrolled. 1,325 were classified as late presenters, showing a high percentage of 57.6% (95% CI: 54.5-60.7%) and a rise (P = 0.004) over the four-year period. Patients with newly diagnosed HIV/AIDS who were older than 24 years of age (aOR = 1.549, P = 0.001 for 25-39 years; aOR = 2.389, P < 0.001 for 40 years and older), were Suzhou registered residents (aOR = 1.259, P = 0.026), and were from inpatient and outpatient (aOR = 1.935, P < 0.001) were more likely to be late presentation. This study showed a high percentage and a rise of late presentation of HIV infection among patients with newly diagnosed HIV/AIDS in Suzhou, China, which is a challenge for future prevention and control of AIDS. Targeted measures should be urgently implemented to reduce late HIV diagnosis.

Late presentation of HIV infection among adults in New Zealand from 2011 to 2020.

Early diagnosis of HIV is essential for successful treatment and controlling HIV spread in a population. We examined the frequency and characteristics of adults diagnosed late with HIV in New Zealand from 2011-2020. Routine surveillance data were analysed. Those previously diagnosed overseas or as part of immigration screening, or with missing CD4 count were excluded. 'Late presentation' was defined as a CD4 count <350 cells/μL or an AIDS-defining event. 'Advanced HIV disease' were those with a CD4 count <200 cells/μL or an AIDS-defining event. Relative risks were calculated using Poisson regression. Of 1145 people, 40.5% presented late; 24.9% had advanced HIV disease. Of the 464 late diagnoses, 65.5% occurred among men-who-have-sex-with-men (MSM), 26.1% among heterosexuals, 8.4% among others. Heterosexual men and women were more likely to present late (55.3%) compared to MSM (35.6%). Amongst MSM, those who were older, of an ethnicity other than European, acquired HIV overseas, tested because symptomatic, or had their last negative test >2years prior were more likely to present late and have advanced disease. Amongst heterosexuals, older age, tested because symptomatic, and Pacific ethnicity were associated with late presentation, and Māori, Pacific and Asian people were more likely to have advanced disease. There continues to be a high proportion of people diagnosed late with HIV. Identifying barriers for testing, missed opportunities for screenings and other factors that delay HIV diagnosis could help develop effective strategies to reduce this burden of late presentation - particularly among heterosexual individuals, non-Europeans, and older people.

Both N- and C-terminal domains of galectin-9 are capable of inducing HIV reactivation despite mediating differential immunomodulatory functionalities.

The shock-and-kill strategy for HIV cure requires the reactivation of latent HIV followed by the killing of the reactivated cellular reservoir. Galectin-9, an immunomodulatory protein, is shown to induce HIV reactivation as well as contribute to non-AIDS- and AIDS-defining events. The protein is prone to cleavage by inflammatory proteases at its linker region separating the N- and C-terminal carbohydrate-binding domains (N- and C-CRDs) which differ in their binding specificities. It is important to study the activity of its cleaved as well as uncleaved forms in mediating HIV reactivation and immunomodulation in order to understand their role in HIV pathogenesis and their further utilization for the shock-and-kill strategy. The PBMCs of HIV patients on virally suppressive ART (n = 11) were stimulated using 350 nM of the full-length protein and N- and C-CRDs of Gal-9. HIV reactivation was determined by analyzing gag RNA copies using qPCR using isolated CD4 cells and intracellular P24 staining of PBMCs by flow cytometry. Cytokine responses induced by the full-length protein and N- and C-CRDs of Gal-9 were also assessed by flow cytometry, Luminex, and gene expression assays. Changes in T helper cell gene expression pattern after the stimulation were also determined by real-time PCR array. Both N- and C-CRDs of galectin-9 induced HIV reactivation in addition to the full-length galectin-9 protein. The two domains elicited higher cytokine responses than the full-length protein, possibly capable of mediating higher perturbations in the immune system if used for HIV reactivation. N-CRD was found to induce the development of Treg cells, whereas C-CRD inhibited the induction of Treg cells. Despite this, both domains elicited IL-10 secretory response although targeting different CD4 cell phenotypes. N- and C-CRDs were found to induce HIV reactivation similar to that of the full-length protein, indicating their possible usefulness in the shock-and-kill strategy. The study indicated an anti-inflammatory role of N-CRD versus the proinflammatory properties of C-CRD of galectin-9 in HIV infection.