Patient activation is determined by an individual’s knowledge, skills and confidence in managing his/her health. It is vital for people living with HIV (PLWH) to enhance their self-management skills and health outcomes, especially those from low- and middle-income regions, since they are at higher risk of worse health outcomes. However, literature from those regions is limited, especially in China.This study aimed to explore the status and factors associated with patient activation among Yi minority PLWH in Liangshan, China and to determine whether patient activation is associated with HIV clinic outcomes.This cross-sectional study included 403 Yi minority people living with HIV in Liangshan between September and October 2021. All participants completed an anonymous survey measuring sociodemographic characteristics, HIV-related information, patient activation and illness perception. Multivariate linear regression and multivariate binary logistic regression were used to explore factors associated with patient activation and the association between patient activation and HIV outcomes, respectively.p < 0.05); those with having disease knowledge learning experiences and an HIV-positive spouse were more likely to have a higher PAM score . A higher PAM score  was associated with viral suppression, mediated by gender .The Patient Activation Measure (PAM) score was low . Participants with negative illness perception, low income, and self-rated antiretroviral therapy (ART) effect based on self-perception were most likely to have a lower PAM score (β = −0.3, −0.2, −0.1, respectively; all Low patient activation level among Yi minority PLWH impacts HIV care. Our findings indicate patient activation is associated with viral suppression for minority PLWH in low- and middle-income settings, suggesting that tailored interventions enhancing patient activation may improve viral suppression. As the prevalence of human immunodeficiency virus (HIV) infection steadily increases, it remains one of the most challenging health issues in the world, particularly in low- and middle-income countries. Globally, more than 37 million people suffer from HIV infection, and over two-thirds of them 25.4 million) are in the low-and middle-income regions . The num million As antiretroviral treatment (ART) became widely available, HIV/AIDS has become a chronic illness, and self-management of HIV-related issues is vital for patients to achieve and maintain viral suppression to facilitate optimal quality of life. Patient activation is determined by an individual’s knowledge, skills and confidence in managing his/her health; this is essential for self-management and health outcomes as it enables patients to actively participate in their healthcare . AccordiIn terms of associated factors, previous studies have confirmed that sociodemographic factors, including educational level, income level, age, gender and disease-related factors, such as illness perception and health status, have an impact on patient activation in chronic disease patients , 10–13. Current studies about patient activation have focused on chronic diseases that are not communicable  ; PreviouThis cross-sectional study was conducted in the main HIV clinic located in Liangshan Yi Autonomous Prefecture, which is a region with the most serious HIV endemic and the poorest economic status in comparison to other places of China. In previous studies, the prevalence of HIV infections has been found to be higher (2.88–9.46%) in Yi minority people in comparison to the Chinese average (0.04%) , 20. In The participants were PLWH seeking care at this clinic, such as obtaining ART medication and undergoing lab tests for viral load and CD4 counts. The inclusion criteria were: having a confirmed HIV diagnosis, being 18 years of age or older, being a member of the Yi minority group and currently receiving antiviral therapy. PLWH who were unable to understand the questionnaire because of cognitive or audio-visual impairment were excluded from participating in this study.The consecutive sampling method was applied to recruit the participants when they came to the clinic for services. PASS software was used to estimate the sample size. Based on a previous study , the staIn this study, the variables included patient activation, illness perception, ART adherence and sociodemographic and disease-related information. The data collection instruments included the 13-item Patient Activation Measure (PAM), the Brief Illness Perception Questionnaire (BIPQ), the Center for Adherence Support Evaluation (CASE) Adherence Index and a sociodemographic and disease-related information questionnaire, as described below.PAM was used to determine the level of patient activation, and we obtained permission from Insignia Health to use this scale. It contains 13 items ranging from strongly disagree (1) to strongly agree (4) on a 4-point Likert scale [9]. Using a revised transformation table provided by Insignia Health, raw scores, in the range of 13 to 52, are calibrated into a total score between 0 and 100 . In a prMeasures of illness perception were obtained using Broadbent and colleagues’ Brief Illness Perception Questionnaire (BIPQ), developed in 2006 . The BIPThe CASE Adherence Index was used to measure adherence to ART . It consA self-made sociodemographic questionnaire was developed to collect data on gender, age, education, marital status, place of residence, employment status and personal income. Disease-related information was also assessed in terms of disease duration, disease knowledge learning experience, spouse’s HIV status, HIV viral load suppression and CD4 count and the self-rated method of ART effect. The question “Have you ever received previous health education about HIV/AIDS ?” was used to measure the disease knowledge learning experience; and the answers included “Yes” and “No.” This variable refers to the experience in taking part in the peer-based HIV education program offered by the clinic, or other similar programs. It is well known that HIV viral load and CD4 count are crucial markers for evaluating the efficacy of ART. Despite this, most of the Yi minority PLWH were unaware of their own CD4 count and HIV viral load based on field observations. Hence, to explore the self-rated method of the ART effect, we devised a question: How do you judge the ART effect? Answers to this question included: (a) by HIV viral load and CD4 count or (b) by self-perception .We found that most of the Yi minority PLWH could not read Mandarin; therefore, we conducted face-to-face interviews using the questionnaire instead of using the self-reported questionnaires. The questionnaires were translated and back-translated independently by two experts (a researcher and a Yi language expert) who are fluent in both Yi language and Mandarin; they were then assessed for cultural relevance and understandability. Data were collected from September to October 2021 by four trained interviewers fluent in both Yi language and Mandarin. All of the interviewers received face-to-face training on the purpose and design of the study, interviewing techniques and role-playing to minimize the interrater differences in using the questionnaires. The participants were approached when they came to the clinic to pick up their medications or receive other medical services.Physicians introduced our project to patients and referred them to a trained investigator for screening and recruitment. A private and quiet room was provided for data collection. The interviewing process usually took between 15 and 25 min for each candidate. Information on the HIV viral load and CD4 count were extracted from each patient’s medical records with permission for the participants and the physicians.sr), the Kruskal–Wallis test or the Mann–Whitney test, depending on the type of data. Multivariate linear regression analysis was conducted on the variables related to patient activation at a significance level of p < 0.05 for the univariate analysis.Descriptive statistics were used to summarize the characteristics of the sample. Mean and standard deviation (SD) were used to describe the continuous variables, and frequencies and percentages were used to summarize the categorical variables. Bivariate associations were analyzed using Spearman’s rank correlation coefficient (p < 0.05) in the univariate analysis were adjusted in the multivariable logistic regression analysis of patient activation and viral suppression. Thus, p < 0.05 (two-sided) was considered significant for the final multivariate analysis. SPSS 23.0  was used for statistical analyses.To test the association between patient activation and HIV viral suppression and CD4 count, univariate and multivariate binary logistic regression analyses were used. The association between patient activation and viral suppression has previously been demonstrated to be mediated by ART adherence . Therefon = 238, 59.1%), married  and residing in rural areas . Educational attainment was fairly low with 93.5% (n = 377) reporting a primary level education or less. Most of the participants were farmers  and most had a personal monthly income of less than US$138 . Among the 403 participants, 87.3% (n = 352) reported self-rated method of ART effect based on self-perception and 86.1% (n = 347) having disease knowledge learning experience. Approximately half of the patient’s spouses  were also HIV positive. The average disease duration was 7.3 years. The mean BIPQ score was 33.33 . The mean CASE score was 14.7 .Among the 409 participants recruited, 403 (98.5%) completed the questionnaire. n = 394); the percentage of patients in Level 2 and Level 3 were 1.7% (n = 7) and 0.5% (n = 2), respectively. There were no Level 4 cases in this survey.The PAM raw score was 29.8 ± 4.1 with a range of 14–45 (corresponding to the transformed score: 39.3 ± 6.0). A comparison of results from this study and previous studies , 17, 27 H = 23.8, p < 0.001) and PAM scores among Yi minority PLWH. For the disease-related variables, the self-rated method of ART effect , having disease knowledge learning experience , spouse’s HIV status  and illness perception  were significantly associated with the PAM score.The results from the multiple linear regression analysis of patient activation are presented in β = 0.2, p < 0.001) and whose spouse was HIV positive , had a significantly higher PAM score. The participants were more likely to have a lower PAM score if their personal monthly income ranged from US$139 to US$414  or was ≤ US$138 , if their self-rated method of ART effect based on self-perception  and if they had a higher illness perception score .The findings indicate that the participants with having disease knowledge learning experience , while it was positively related to viral suppression .Of the 403 participants, 387 reported HIV clinical outcomes in terms of CD4 count and viral suppression . Among these, 280 (72.4%) participants achieved viral suppression and 326 (84.2%) achieved a CD4 count ≥200 cells/mLp = 0.011) remained positively related to viral suppression, and the relationship was mediated by gender . However, ART adherence was not significantly related to viral suppression.To the best of our knowledge, this is the first study to explore the status of patient activation and its correlation with health outcomes  in Yi minority PLWH in China. We found three key findings in our research. First, the PAM score was extremely low, which is contrary to the findings reported in previous research conducted in high-income countries. Second, lower personal monthly income, self-rated method of ART effect based on self-perception and a higher illness perception score were associated with a lower PAM score. Having disease knowledge learning experience and spouse’s positive HIV status were related to a higher PAM score. Third, a higher PAM score was related to viral suppression, mediated by gender. To achieve optimal HIV self-management, these findings are critical to improving patient activation in low- and middle-income settings.In this study, patient activation status was found to be different from that reported in previous studies. The level of PAM in Yi minority PLWH is much lower than in studies conducted in Western countries, such as the United States  and CanaWe found that lower personal monthly income, self-rated method of ART effect based on self-perception and higher illness perception score were associated with a lower PAM score. It is not surprising that lower personal monthly income is a risk factor for a low PAM score, which is consistent with the findings reported in previous studies that the income levels of participants are related to patient activation . ParticiHaving disease knowledge learning experience and a spouse’s positive HIV status were predictors of a higher PAM score. In this context, the PLWH with having disease knowledge learning experience from a brief peer-based HIV knowledge education program organized weekly in the clinic, but part of the sample did not have the opportunity to participate in this program. According to several previous studies of chronic disease patients, providing patients with knowledge about their disease can significantly improve the PAM score , 36. We We found higher PAM scores were associated with HIV viral suppression, which was mediated through gender, but they were not associated with CD4 count [that finding was partially supported by a previous study ]. UnexpeUnexpectedly, inconsistent with the previous studies, our study did not find that the ART adherence mediated the relationship between patient activation and viral suppression. Overall, ART adherence was good among the Yi minority PLWH who participated in this study. This finding could be due to the fact that self-health management knowledge and skills , other than maintaining good adherence, were ignored by the Yi minority PLWH with low patient activation. Our findings indicate that simply maintaining good ART adherence is not enough for this lifelong illness, and tailored patient activation interventions are necessary to improve health outcomes in minority PLWH with low patient activation.Our study has several limitations that should be considered when interpreting the results. First, we were unable to draw causal inferences from our study due to its cross-sectional design, because it was not possible to examine whether the detected associations persist over time. Although our findings identify several factors related to patient activation and the relationship between patient activation and HIV viral suppression, a longitudinal study is needed to explore the relationship accurately. Second, we primarily included participants engaged in care in an HIV treatment clinic; these participants had a better adherence to treatment and had access to professional medical consultation, education and care for their health management. However, it is likely that PLWH who are not receiving care have lower PAM scores and are more vulnerable, as they have less access to professional support. Thus, future studies should include these individuals to reinforce the observed relationships between patient activation and other variables. Third, there are considerable differences in terms of ethnicity, culture, local language and public health system among low- and middle-income regions. Thus, caution is needed when generalizing the findings of our study to other populations of PLWH . Fourth,Patient activation is poor in Yi minority PLWH, and the factors we identified included personal monthly income, self-rated method of ART effect, illness perception, having disease knowledge learning experience and spouse’s HIV status. Moreover, a higher PAM score was associated with viral suppression. Our findings will help healthcare providers systematically evaluate these factors to identify individuals with low patient activation. These research findings may also be used to develop interventions for minority PLWH in low- and middle-income regions to increase their involvement in the healthcare system, and they suggest that viral suppression may be improved by facilitating an increase in patient activation.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The Institutional Review Board of Xiangya Nursing School of Central South University approved this study (No. E2021007). During the study, all participants provided informed consent and participated voluntarily after a detailed explanation of the study aims. A written informed consent  was required to enroll. The participants were not paid for their participation.WeA conducted the study design, data collection, analysis and interpretation of the data, and wrote the manuscript. XT, XX, and WaA contributed to the data collection, analysis, and interpretation, and commented on drafts. HW supervised the study design, data collection, analysis and interpretation of the data, and commented on the draft article. All authors contributed to this article and approved the submitted version.This work was supported by the Provincial Natural Science Foundation of Hunan Grant (No. 2022JJ30769); and the School-level Projects of Panzhihua University (No. 2021PY003).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Achieving viral suppression (VS) for persons living with HIV is key to reaching epidemic control. We assessed the prevalence of VS and the frequency of HIV drug resistance mutations (HIVDRM) among children and adolescents living with HIV (CALHIV) in the Southern Highland zone of Tanzania.From 2019 to 2021, we enrolled CALHIV aged 1–19 years on ART for >6 months in a cross-sectional study. Participants had viral load (VL) testing; those with VL ≥ 1000 copies/mL underwent HIVDRM testing. VS (<1000 copies/mL) prevalence estimates were calculated and robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations with potential predictors of VS.Of 707 participants, 595 had VS . Use of an integrase strand transfer inhibitor-containing regimen , age 5–9 years , and seeking care at a referral center  were associated with VS. Factors inversely associated with VS included having one  or two or more  referrals for adherence counselling, and self-reporting missing one to two  or three or more  doses of ART in the past month. Of 74 participants with PRRT and INT sequencing done, 60 (81.1%) had HIVDRMs at the following frequencies: 71.6%, 67.6%, 1.4%, and 4.1% for major NNRTI, NRTI, PI, and INSTI respectively.Higher rates of VS were observed in this cohort, and HIVDRMs were common in those without VS. This evidence supports ART optimization using dolutegravir-based regimens. However, better strategies to improve adherence are needed. In 2020, the Joint United Nations Program on HIV/AIDS (UNAIDS) estimated that there were 2.78 million children and adolescents living with HIV (CALHIV) globally, and they accounted for 10% of new infections and 15% of AIDS-related deaths .The goal of ART is durable viral suppression (VS), with subsequent restoration of the immune system, and reduction in mortality and HIV transmission . In 2014Failure to attain the UNAIDS third “95” target among CALHIV continues to pose a challenge to epidemic control, as studies have reported lower VS rates in this sub-population compared to adults , 14, witOur primary objective was to estimate the prevalence of VS among CALHIV in the Southern Highlands of Tanzania. Additionally, the study sought to identify factors associated with VS and describe HIVDRMs occurring among participants.Random sampling was conducted on lists of eligible participants on ART between 2019 and 2021 at 15 treatment clinics  supporteParticipants underwent a blood draw for HIV VL unless test results for routine clinical care within 1 month of study enrollment were available. We also included viral loads that were outside the original 1 month window for participants without a recorded viral load value within the month prior to enrollment. During the study visit, study staff administered sociodemographic questionnaires to participants aged ≥18 years, to caregivers if the participant was younger than 13 years, and to both caregivers and participants if the participant was between 13 and 17 years. Information on the clinical history and ART records from written files, electronic clinical and pharmacy systems, and ART registers for each participant were abstracted by the study team within 3 weeks of the participant’s visit. Data from medical record abstraction captured information and events prior to enrollment into the study. Referral history captured documented referrals for adherence counselling and other relevant support services documented in the charts. However, source documentation did not include information on whether participants received the services for which they were referred. Data were transcribed onto case report forms and entered into the Clinplus platform .The study was approved by institutional review boards of the Walter Reed Army Institute of Research, Baylor College of Medicine, Mbeya Medical Research and Ethics Committee, and the Tanzania National Institute for Medical Research. All participants provided informed consent and assent, as applicable.HIV VL was measured via nucleic acid amplification methods on the Abbott m2000sp/rt RealTime HIV-1 assay  System with a reportable range of –10 000 000 copies/mL.Plasma samples from all participants with VL ≥ 1000 copies/mL underwent sequencing of the Pol region using a laboratory-validated modification to the ViroSeq HIV-1 Genotyping System v2.0 . Sequences were evaluated for major mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs), NNRTIs, protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTI) using the SmartGene Integrated Database Network System  to access mutation lists from the Stanford HIV Drug Resistance Database Version 8.8.0 .Extraction of viral ribonucleic acid (RNA) from the samples was performed using Purelink™ Viral deoxyribonucleic acid (DNA)/RNA Minikit, and HIV genotyping was performed using ThermoFisher HIV-1 Genotyping kit with Integrase—for PR, RT, and INT genes. GeneAmp® 9700 polymerase chain reaction (PCR) system thermocyclers were used for PCR procedures, and final sequence detection was performed using ABI 3500xL Genetic Analyzer.Sequence raw data were analyzed using online RECall software (version 2.32) for reviewing base-calling, sequence editing, and generation of consensus sequences. For sequence quality control (QC), MEGA-X software (Version 10.2) was used for assessing genetic distance among the samples by pairwise alignment. HIV subtyping QC was performed using REGA, National Center for Biotechnology Information (NCBI), Stanford and Jumping HIV subtyping tools, and the generation of final HIV drug resistance reports was done by using the Integrated Database Network System (IDNS) Smart gene software.HIV-1 subtype was inferred from the consensus evolutionary tree from SmartGene IDNS, which utilizes the neighbor-joining method in MEGA4 software. Evolutionary distances were computed using the maximum composite likelihood method in units of the number of base substitutions per site. The tree was then generated by the neighbor-joining method from a nucleotide alignment. All testings for VL and HIVDRMs were performed according to the manufacturer’s instructions at the Mbeya Zonal Referral Hospital Laboratory in Mbeya region, Tanzania.α < 0.05) in the unadjusted models and those identified based on a priori and clinical knowledge of the study setting were included in the fully adjusted model. Predictors identified a priori included sex, age, and duration of ART and ART class. We tested for multicollinearity using the variable inflation factor; no variables were found to be collinear. Additional predictors identified in bivariate analyses were included in the adjusted models. Analyses were restricted to complete cases after creating separate categories for unknown data from participant medical records . For participants with a VL ≥ 1000 copies/mL, the prevalence of specific HIVDRMs and categories of HIVDRMs were calculated by dividing the number of participants with one or more mutations by the total number of participants genotyped.VS was defined as VL < 1000 copies/mL . The preAnalyses were performed in Statistical Analysis System (SAS) version 9.4  and Stata version 16.1  software.Randomization identified 785 CALHIV as potential participants for the study and was screened for eligibility, of which 774 were fully eligible for enrollment. Of those 774 and 747 were successfully contacted by the study team, agreed to participate, and were enrolled. However, only 707 (94.6%) had complete case data and were included in further analyses. The median age was 12 (interquartile range-IQR: 9–16) years and 382 (54.0%) were female . Twenty-At enrollment, a total of 290 (41.0%) participants were on an ART regimen with an abacavir ABC/3TC backbone, 54 (7.6%) were on an AZT/3TC backbone, and 363 (51.3%) were on a TDF/3TC backbone regimen, including 339 (93.4%) who were on TDF/3TC/DTG. There were 405 (57.3%) on first-line and 302 (42.7%) on second-line therapy.A total of 103 (14.6%) participants had documented a history of one referral for adherence counselling, while 49 (6.9%) had been referred two or more times for adherence counselling. Referrals for other services, not including adherence counseling, were documented for 235 (33.2%) participants. At the time of study enrollment, 631 (89.3%) were well nourished and 570 (80.6%) self-reported no missed doses of ART in the month preceding enrollment. The distribution of ART use across the age bands revealed significant differences in the current ART class and current NRTI backbone by age . ART regThe overall prevalence of VS was 0.84  for NNRTIs, 67.6% (n = 50) for NRTIs, 1.4% (n = 1) for PIs and 4.1% (n = 3) for INSTIs. The K103N was the most common NNRTI mutation at 36.5% and the M184V/I was the most common NRTI mutation at 60.8%. The only PI-related mutation detected was the N83D and the only INSTI-related mutation detected was the R263K (Of the 117 CALHIV who was unsuppressed (not restricted to complete cases), samples from 74 (63.3%) had successful PRRT and INT sequencing completed. Of these 74 participants, 60 (81.1%) had any major HIVDRM. In addition to their NRTI backbone, 12 (16.0%) were on an NNRTI; 21 (28.0%) on PI; and 41 (56.0%) on an INSTI-based ART regimen. Class-specific HIVDRM prevalence was 71.6% (he R263K .n = 36 n = 11), D , and recombinant forms .The subtype distribution was heterogeneous with subtype C predominating  . A sistePrevious research has identified adolescents as having worse adherence and other key outcomes , 27. ThiWe found that non-adherence negatively impacted VS in our study, with the youngest age band reporting the highest percentages of missed doses of ART in the month prior to enrollment. Effective long-term solutions for medication adherence remain elusive among CALHIV and continue to be a priority for treatment programs. The Tanzania guidelines recommend adherence assessments at every clinic visit. These sessions explore reasons for poor adherence, the patient’s support system, and medication routine, with modifications to meet client-based needs at the facility and community levels . DespiteAdherence to ART for CALHIV may remain suboptimal until more pediatric-friendly treatment regimens become globally available. Palatability and complex dosing regimens have consistently been shown to greatly affect pediatric adherence . Recent in vitro by DTG and other INSTIs [We found a widespread occurrence of NNRTI and NRTI mutations among our participants with viral non-suppression. Prior to the rollout of DTG-based regimens, efavirenz and nevirapine-based regimens were the mainstay of ART in resource-limited settings. The migration to more optimal drugs was informed by the low-genetic barrier of and early emergence of HIVDRMs to NNRTIs. Despite the positive association between INSTI-regimens and VS reported in this study, we found a 4.1% prevalence of the INSTI-related R263K; a nonpolymorphic mutation selected r INSTIs . A recenr INSTIs . Taken tr INSTIs , 24.Due to the cross-sectional study design, only associations with regard to VS could be made. Follow-up studies to assess trends in VS are needed. Since this study was conducted only in PEPFAR-supported sites, it may lack generalizability to other areas with different levels of resources. Additionally, this study’s method for measuring adherence by self or caregiver report likely underestimates the true rate of nonadherence . SpecifiThis study demonstrated 84% VS prevalence among CALHIV in Tanzania; a significant improvement compared to earlier studies in East Africa. Further exploration of associations with failed VS shown in the study may suggest potential interventions to bring the VS rate up to the UNAIDS’ goal of ≥95% VS. Prospective studies focused on areas such as the effectiveness of the EAC program, characteristics of those failing on INSTI-regimens and the quality of care at lower level facilities would potentially allow for interventions that provide better, patient-centered care for those still not meeting VS thresholds. Regardless, this study supports WHO guidelines on the need to optimize children on INSTI-containing regimens.piad040_suppl_Supplementary_Figure_S1Click here for additional data file.piad040_suppl_Supplementary_Table_S1Click here for additional data file.piad040_suppl_Supplementary_Figure_LegendClick here for additional data file.


More than 30,000 cases of mpox have been identified in the United States. Data suggest that about 40% of affected persons are co-infected with HIV. Although most cases are self-limiting, patients with low CD4 counts are at increased risk of developing severe clinical manifestations and dying.Retrospective case-control study comparing mpox cases among people with HIV (PWH) and HIV-uninfected persons from July to Dec 2022, at Henry Ford Health in Southeast Michigan. Demographic data, clinical characteristics, treatment, and outcomes were evaluated.54 patients were diagnosed with mpox. Overall, 42 (78%) were MSM or bisexual men, 36 (67%) Black, and 34 (63%) PWH; median age was 34.5 years (Table 1). The majority (63%) had prior sexually transmitted infections (STIs), which were more common in PWH . About one-third had multiple sexual partners; more than half engaged in insertive or receptive anal intercourse. 32 (94%) of PWH were on ART, 26 (76%) had CD4 counts >200 and 19 (60%) had undetectable viral load; mean CD4 count was 602 and viral load 7942. Of the HIV-uninfected persons, 5 (25%) were on PrEP. Receipt of mpox vaccine was uncommon in either group. All patients presented with rash that was disseminated in 35%. Fever/chills, lymphadenopathy, headache, proctitis and pharyngitis were the most common manifestations and did not differ among the two groups. Concomitant STIs were present in 22 (48%) of 46 persons tested; syphilis co-infection was more prevalent among PWH . Hospitalization and receipt of tecovirimat were similar between the two groups; no patients died.Demographics, Risk Factors, Clinical Manifestations and Outcomes of Mpox PatientsOverall, there were no significant differences in clinical manifestations or outcomes between PWH and HIV-uninfected persons with mpox except for syphilis co-infection. Most of our PWH cohort was on ART and virally suppressed with high CD4 count. Hence, efforts should focus on rapid treatment of PWH with effective ART to achieve virological suppression and immunological recovery to minimize clinical complications and severe outcomes associated with opportunistic pathogens. Vaccinating all high-risk individuals, early mpox recognition and testing, and screening for additional STIs should be prioritized.Indira Brar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria


Neurocognitive disorders due to human immunodeficiency virus (HIV) remain highly prevalent, specifically mild forms despite effective antiretroviral therapy (ART). Dolutegravir-based regimens are the first line of treatment for adult HIV-positive patients. Controversies exist regarding the neurocognitive effects of dolutegravir. Evidence regarding the neurocognitive effects of dolutegravir is important, in support of its use in patients with HIV-associated neurocognitive disorders (HAND).This study aimed to describe the change in cognitive function using the International HIV Dementia Scale (IHDS) and Brief Neuropsychological Cognitive Examination (BNCE) in HIV positive, treatment naïve patients before and 3 months after initiation of ART using a dolutegravir-based regimen.The HIV initiation clinic of Hillbrow Community Health Centre in Johannesburg.This prospective, quantitative cohort study assessed adult HIV-positive patients who were ART naïve being initiated on a dolutegravir-based regimen, using the BNCE and IHDS at baseline and after 3 months of treatment.Z = 1.84, p = 0.033) and time to complete BNCE . BNCE total results showed improvements that were not significant ; however, Part 2 of the BNCE reflecting that of executive function showed significant improvements .Neurocognitive test results of 26 participants showed significant improvements for IHDS (The trend of neurocognitive function is towards improvement in HIV-positive treatment naïve patients who receive 3 months of dolutegravir-based ART.The findings support the use of dolutegravir-based regimens in the treatment of patients with HIV-associated neurocognitive disorders.HIV-associated neurocognitive disorders; BNCE; IHDS; dolutegravir; neurocognitive screening; neurocognitive impairment; South Africa. It was hypothesised that results would show improvement. Secondary objectives included to compare patient sociodemographic data  as well as blood results, specifically baseline CD4 count and viral load (VL) measured at 3 months post-ART initiation and correlate these findings to change in neurocognitive results.This study was a prospective, quantitative and descriptive cohort study. It was conducted between June 2021 and July 2022 at the HIV initiation clinic at Hillbrow Community Health Centre in Johannesburg. This unit falls under the district level of care in the public health sector of the Gauteng Department of Health in South Africa.The study sample population comprised English-speaking and consenting, adult HIV-positive patients who were ART naive being initiated on a dolutegravir-containing regimen. Exclusion criteria consisted of any previously diagnosed neurocognitive disorder or the presence of other known causes of neurocognitive impairment such as depression, stroke, intellectual disability, traumatic brain injury and current or recent substance use. Patients older than 60 years were excluded from the study to preclude age-appropriate neurocognitive decline as a confounding factor. The calculated required sample size was 33 participants to achieve significant results with a certainty of 95%. The intended sample size was 50 participants to account for participant dropout and other unforeseen circumstances. Patients attending the HIV initiation clinic were chosen by stratified sampling. Adult patients who were ART naïve and to start a dolutegravir-containing regimen were given information regarding the study by use of a pamphlet and provided written consent to participate in various aspects of the study. A screening questionnaire was then provided comprising inclusion and exclusion criteria. Eligible participants were allocated a participant number and included in the study.5 The maximum score is 12 with scores of 11 or 12 considered normal and scores of 10 or lower indicating need for further neuropsychological testing. The second test, the BNCE, is made up of two parts with five subtests in each part. Part 1 subtests are mainly related to conventional types of information processing  and Part 2 subtests are aimed at assessing the performance of executive functioning.18 Specific to the South African population, modification of Part 1, section B of the BNCE titled presidential memory was required, in order to be appropriate to the knowledge and culture of the study group. Questions were adapted from assessing presidential memory of the United States to that of African presidential history that is well known to the people of South Africa. This maintains a culturally fair and appropriate measure of long-term memory and crystalised intelligence, in the absence of other culturally appropriate tests. The maximum score is 30 with total scores of 27 or less indicating cognitive impairment. Scores are then further divided into mild (22–27), moderate (10–21) and severe (0–9).18 The time taken to complete the BNCE was also considered in evaluating cognitive improvement. This is not a requirement for the administration of the BNCE, however, is useful when assessing processing speed in the consultation.18 Neurocognitive testing was conducted on the day of ART initiation and repeated after approximately 3 months after confirming treatment adherence. Blood results were documented, specifically CD4 count at baseline and VL after 3 months of receiving ART.The primary investigator collected and documented demographic information and assessed participants using the IHDS and BNCE. The IHDS screening tool is a three-part examiner administered test comprising of a non-dominant finger-tapping test, a non-dominant Luria hand sequence and a four-word recall test.www.R- project.org).Of the 63 participants that completed the screening questionnaire, data from a total of 26 participants were used in the analyses. These participants completed the 3-month follow-up to produce useable data to address the aims of the study. The data were collated in Microsoft Excel™ and statistically analysed in R software , logistic regressions for dichotomous outcomes, general linear regressions and Wilcoxon matched pairs tests . Some analyses were one-tailed based on directional hypotheses (e.g. Wilcoxon tests), and all other analyses were two-tailed. Model alpha was set at 0.05. Data are reported as counts and percentages  or mean and standard deviation (continuous data) and presented descriptively in the text, tables and figures.19 Approval was also granted by The National Health Research Database (Ref: GP_202008_151). Written consent was obtained from all individual participants involved in the study. Confidentiality was maintained by the removal of identifiable information and use of participant numbers.Ethics clearance was obtained from the University of Witwatersrand Human Research Ethics Committee (Clearance Certificate No. M201102). All procedures performed were in accordance with the 1964 Helsinki Declaration and it’s later amendments.Of the 63 patients screened for participation, 38 were eligible. Excluded participants comprised mostly males and the majority due to substance use. After a loss to follow up drop out rate of 31, 6%, 26 participants completed the study . The day2 = 9.85, df = 1, p = 0.002) and all were black African ethnicity. The years of formal education ranged from 7 to 14 years with a mean of 11.0 (s.d. = 1.7) years. CD4 counts were found to have a mean of 304.1 (s.d. = 228.2) cells/mm3 and when categorised into below or above counts of 200 cells/mm3, the difference was not significant . The viral load measured at 3 months varied with significantly more patients showing virological suppression at levels of 0–20  (The demographic data as depicted in = 0.032) .Z = 1.84, p = 0.033)   (The neurocognitive tests at baseline and at 3 months showed that IHDS results increased significantly from a baseline mean of 8.3 (s.d. = 1.6) to a 3 month mean of 9.1 (s.d. = 2.1) (Wilcoxon test: = 0.033) . The BNC= 0.075) . In cont= 0.007) .Z = 297.5, p < 0.001) and BNCE 2    . At base< 0.001) . When co= 0.043) .p = 0.009). The BNCE score at baseline also decreased with every year of increasing age; however, this was not found to be significant (p = 0.065). Years of education were found to be a significant predictor of both IHDS and time taken to complete BNCE. A one year increase in years of education increased the IHDS 1 and 2 scores significantly . Similarly, with every 1 year increase in years of education, the time taken to complete the BNCE decreased both at baseline and 3 months later . While BNCE total scores at baseline and 3 months were also found to increase with every year of education, this was not found to be significant . The correlation between socio-demographic variables and improvement in neurocognitive test scores was not found to be significant  and decrease in time taken to complete the BNCE (p = 0.015). In comparison, those with CD4 counts of > 200 cells/mm3 showed no significant change in IHDS, BNCE and time scores  (Participants with a baseline CD4 count of < 200 cells/mmctively) .No significant correlation was found between VL measured at 3 months and improvement in neurocognitive test results .20 The authors concluded that while 6 months was long enough to see VL suppression in both plasma and CSF, this may not be enough time to confirm change in cognitive function.20 The time factor may explain the findings in that not enough time was allowed for all aspects of cognition to improve between testing. Cysique et al. found that cognitive improvement can start as early as 12 weeks; however, it occurs more often between 24 and 48 weeks.3 In order to detect clinically appreciable differences, a follow-up of longer than 2 years is suggested.21 Another factor to consider is the time to improvement of specific domains of cognitive function. It is well known that HIV primarily impacts functions of subcortical and striatal brain regions, namely executive function, motor and information processing speeds and memory recall.5 The IHDS is limited to the evaluation of motor speed, memory recall and psychomotor functions.22 In contrast, the BNCE covers a broader range of cognitive functions with a specific focus on executive function.17 It is not clear which aspects of cognitive function are first to improve with ART with some short-term studies showing improvement in all domains except motor processing speed.23 This is an area requiring further research. Another explanation for the findings could be that high rates of persistent milder forms of neurocognitive impairment are commonly seen despite adequate ART with the BNCE being more appropriate in its recognition.24This study aimed to describe the changes in cognitive function at baseline and 3 months after initiation of ART using a dolutegravir-based regimen with the hypothesis that results would show improvement. Significant improvements were noted in both IHDS scores and time taken to complete the BNCE. This supports improvement in subcortical neurocognitive function tested in the IHDS, as well as processing speed indicated by the time taken to complete the BNCE. While the total BNCE scores did show improvements from baseline, these results were not found to be significant. This is consistent with findings from a study done in 2020 assessing change in cognitive function over a 6 month period of using dolutegravir as assessed by the Montreal Cognitive Assessment (MoCA).18 In assessment of HAND, one can expect Part 1 scores to be relatively preserved and Part 2 scores to show deterioration, with the difference being more pronounced in severe disease.18 Results confirmed this in that majority of participants had lower scores in Part 2, confirming the subcortical origin of pathology as well as emphasising the burden of mild neurocognitive impairment based on point discrepancies found between the two parts. In moderate to severe dementia, the score in Part 2 shows earlier and quicker deterioration and with disease progression is expected to remain consistently lower than Part 1 scores.18 Interestingly, the results show improvement of BNCE part 2 scores at 3 months and a lower percentage showing the larger discrepancy between the two parts. This trend is in keeping with the subcortical origin of HAND and the quicker deterioration and therefore improvement with treatment in these areas of cognition. Results also show more improvement in Part 2 than Part 1 scores. This confirms that significant improvement in certain areas of cognitive functioning is taking place over the short period examined. However, this does not equate to overall improvement in cognitive functioning.The BNCE’s advantage over other screening tests is its ability to assess both conventional, frequently used cognitive functioning as well as more advanced levels of executive functioning allowing for detection of milder forms of cognitive impairment.25 This is considered as having high CNS penetration.25 While higher CPE scores are associated with improved control of viral replication in the CNS, its correlation to neurocognitive impairment remains controversial with ongoing concern of neurotoxicity.25 Despite this possibility, a recent study concluded that ART with higher CPE is associated with modest improvement in global neurocognitive functioning, with less improvement noted in specific cognitive domains such as attention, working memory and learning.26 This could explain why significant improvements were noted in the IHDS and processing speed and not in BNCE with its strong emphasis on higher orders of cognitive function. Overall, it has been found that higher CPE regimens are slightly more likely to preserve or improve cognitive function than regimens with lower CPE scores.26 Research comparing dolutegravir-based regimens with other regimens of lower total CPE value would be beneficial.With the focus of this study on dolutegravir, which when combined in the currently recommended regimen, contributes four points to a total CPE score of seven.26 It occurs in 4% – 20% of patients treated with ART, with some experiencing ongoing neurological symptoms.26 This could explain the findings of lack of correlation between neurocognitive improvement and serum VL suppression.Cerebrospinal fluid viral escape should also be considered in assessing effects of CPE on neurocognitive function. This occurs when plasma viral suppression is achieved, while CSF viral replication continues.21 Evidence also shows that age-related cognitive decline is exacerbated by HIV.10 Although the study excluded participants over the age of 60 to account for age-related decline in cognition, some elements of executive function have been found to start declining as early as 45 years of age.27 This could also explain why we see a correlation between increasing age and BNCE results and we do not see the same correlation with IHDS results, with its limited assessment of executive function. Another aspect to consider with increasing age is that drug pharmacokinetics may be less effective, negatively impacting the relationship between CPE score and neurocognitive improvement.26As expected, cognitive test results of BNCE were lower with increasing age. In the ageing HIV population, both accelerated and natural decline can be seen due to multiple factors, with AIDS as the predominant cause and hence expectation is to see a negative effect of age on cognitive function despite adequate treatment.27 This study confirmed that for each year increase in years of education, there was an increase in neurocognitive score as well as faster processing speed.The cognitive reserve hypothesis holds that factors such as higher levels of education, socioeconomic status and baseline intelligence can be protective against clinical manifestations of brain pathology.8 This study did not find any correlation between gender and neurocognitive function; however, this could be affected by over-representation of female participants.Research regarding gender as a risk factor for neurocognitive impairment is conflicting.28 This study confirms that those with lower baseline CD4 counts were more likely to show improved neurocognitive scores and processing speed 3 months after receiving treatment. This could be accounted for by the association of baseline CD4 cell counts of less than 200 cells/mm3 with increased proliferation of HIV within the CNS.29 Another consideration is the possibility of delirium at baseline prior to the initiation of ART. Risk factors for delirium include the presence of neurocognitive impairment as well as acute and opportunistic infections, which more commonly occur with advanced immunosuppression.30 In contrast, multiple studies have found that markers of advanced HIV such as lower CD4 counts were not a significant risk factor for delirium.30 The results support early initiation of ART to assist with various degrees of neurocognitive impairment.Many large studies have confirmed that a low nadir CD4 is an indicator of neurocognitive impairment as well as a predictor for future diagnosis of HAND.This study contributes towards the growing evidence regarding effects of ART on neurocognitive function as well as the need for more evidence around the use of dolutegravir.31 These factors increase the false-positive rate of HAND diagnosis, questioning the validity of the current criteria with a move towards more emphasis on clinical diagnosis.31Limitations included a small sample size with a significant female predominance, which may have impacted on some results noted. Additionally, the BNCE required adjustments to make the test culturally appropriate. While this is the approach taken in practice and necessary to ensure the suitability of the test to South Africans, construct validity of these changes has not been established. Furthermore, a control group for comparison would have been useful to account for practice effects when interpreting improvements in results. This is an area for further research. It is also acknowledged that complex multifactorial factors contribute towards low cognitive test performance, including socioeconomics, quality of education and comorbidities.Based on the findings, one can conclude that the trend of neurocognitive function is towards improvement in HIV positive, treatment naïve patients who receive 3 months of dolutegravir-based ART. While the dolutegravir cannot be implicated as the main factor contributing towards improvement, the findings support the use of dolutegravir-based regimens in the treatment of patients with HIV-associated neurocognitive impairment. Future research should aim at assessing patients over a longer period to confirm clinically significant improvements. Comparison to other regimens would also be beneficial.


Cabotegravir (CAB) + rilpivirine (RPV) is the first recommended complete long-acting (LA) regimen for maintenance of HIV-1 virologic suppression. The efficacy and safety of switching to CAB + RPV LA (CAR) has been shown in clinical trials. CAR injections offer less frequent dosing and address issues of adherence and disclosure related to daily oral cART. We describe the clinical characteristics and outcomes of switching a diverse group of people with HIV (PWH) to CAR in a real-world setting.A retrospective cohort study was performed to assess virologic efficacy of intramuscular CAR given every 4 or 8 weeks among adult PWH receiving care at Henry Ford Health ID Clinic by an interdisciplinary team of physicians, nurses, social workers, and a pharmacist. Efficacy was defined as HIV-1 RNA < 20 copies/mL at 3 months. Demographics, clinical characteristics, and outcomes were extracted from the electronic medical record.We included the first 51 patients to receive CAR. Median age was 46 years (IQR 34 -59). Black individuals were 75%, cisgender males 84%, and transgender females 3.9% of participants. PWH were diagnosed a median of 12 years ago (IQR 11-17). At time of switch, 90% had HIV viral load (VL) < 20 copies/ml, and 9.8% of patients were viremic with < 75 copies/ml. Mean Cd4+ cell count was 871 cells/µL (IQR 632-1603). Prior to switch, 80% had received ≥ 2 cART regimens, 75% had INSTI exposure, and 45% had NNRTI exposure. Among 38 patients with HIV-1 genotypes available prior to switch, 4 had either baseline NNRTI or INSTI mutations (Table 2). For patients with VL data at 3 months, 37 of 38 (98%) had an undetectable VL. Virologic failure occurred in 1 PWH with BMI 35 who had a Y188L RT mutation in a 2009 genotype which did not include RPV , with subsequent emergence of pan-NNRTI and INSTI resistance.A high degree of virologic suppression at 3 months was achieved among an older, diverse cohort of PWH cared for by an interdisciplinary team. Unrecognized baseline HIV resistance to NNRTI contributed to one virologic failure. It is important to assure that genotypic susceptibility interpretations are current and to carefully assess for eligibility before switching to CAR.John Di Lodivico, PharmD, Midwest AIDS Training & Education Center: Honoraria|ViiV Healthcare: Advisor/Consultant|Wayne State University: Honoraria Indira Brar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria


Antiretroviral therapy (ART) has significantly reduced mother-to-child transmission of HIV among pregnant women. Nonetheless, numerous factors can impede ART adherence and thus virologic suppression (HIV RNA < 200 copies/mL). Although there are limited data on current rates of virologic control in women with HIV around pregnancy, previous studies have highlighted lower rates at the start of pregnancy and 6 months postpartum. The objective of this study was to compare virologic suppression rates in women pre-pregnancy, intrapartum, and postpartum at a clinic serving a marginalized community and to identify factors associated with virologic controlThis study was a single-center, retrospective chart review including pregnant patients receiving care at a hospital-based, NJ Ryan-White funded clinic between 2015-2022. The primary endpoint was to determine whether there is a difference in the proportion of patients with virologic suppression at the start of pregnancy, at delivery, and 6 months postpartumAt the first visit, 64.4% of mothers were virologically suppressed. Our study found that the proportion of women remaining virologically suppressed was lower at 6 months postpartum compared to the time of delivery , regardless of virologic suppression at the first visit. Older age at pregnancy was associated with improved virologic suppression at 6 months postpartum . However, perinatal HIV acquisition, as compared to heterosexual acquisition, was correlated with increased virologic failure at 6 months postpartum .Although a high percentage of patients were controlled at delivery, the drop in virologic suppression postpartum highlights the need for additional efforts to support the mother and child during that time. While further research is warranted to identify further confounders that may impact virologic control and other barriers to care, the healthcare team should work together holistically on frequent outreach and follow up during the entire pregnancy.All Authors: No reported disclosures


Limited data suggest intensive care unit (ICU) outcomes have improved in people with HIV (PWH). We describe trends in in-ICU/in-hospital mortality among PWH following admission to ICU in a single UK-based HIV referral centre, from 1 January 2000 to 31 December 2019.+ T-cell count and diagnosis of HIV at/within the past 3 months.Modelling of associations between ICU admission and calendar year of admission was done using logistic regression with adjustment for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, CD4+ T-cell count were 19 [14–25] and 122 cells/μl [30–297], respectively; HIV-1 viral load was ≤50 copies/ml in 46%. The most common ICU admission diagnosis was lower respiratory tract infection (30%). In-ICU and in-hospital, mortality were 29 and 38.5%, respectively. The odds of in-ICU mortality decreased over the 20-year period by 11% per year [odds ratio (OR): 0.89 : 0.84–0.94)] with in-hospital mortality decreasing by 14% per year [0.86 (0.82–0.91)]. After adjusting for patient demographics and clinical factors, both estimates were attenuated, however, the odds of in-hospital mortality continued to decline over time .Among 221 PWH ] age 45 years [38–53]) admitted to ICU, median [IQR] APACHE II score and CD4Short-term mortality of critically ill PWH admitted to ICU has continued to decline in the ART era. This may result from changing indications for ICU admission, advances in critical care and improvements in HIV-related immune status. The prognosis for people with HIV (PWH) has improved markedly since the introduction of effective combination antiretroviral therapy (ART) in the 1990s, although contemporary data describing this positive trend over time are limited . Further+ T-cell count <200 cells/μl, newly diagnosed HIV-1 infection, lack of receipt of ART, respiratory failure, renal failure and the need for mechanical ventilation  age at admission over the study period, increasing from 40 years [35–46] in 2000–2003 to 49 years [40–57] in 2016–2019 . There was also evidence of an increasing linear trend in the percentage of patients that had an undetectable viral load (≤50 copies/ml), with higher percentages observed in the later year groups, increasing from 16.7% in 2000–2003 to 52.5% in 2016–2019 (P-trend = 0.02). In contrast, there was strong evidence of a decreasing linear trend in the median APACHE II score, with lower scores in the later year groups, decreasing from 29 [IQR 23–31] in 2000–2003 to 15 [IQR 10–20] in 2016–2019 (P-trend < 0.001) (Table There was evidence of an increasing linear trend in the median CD4P-trend = 0.85). Median time since HIV diagnosis was also variable over the study period, but tended to increase in the latter years, with the shortest median time interval since HIV diagnosis observed in 2004–2007 (28 months [IQR 1–97]) and longest in 2012–2015 (116 months [IQR 3–207]); and there was little evidence of an increasing linear trend (P = 0.06). There was strong evidence of a notable decreasing linear trend in the percentage of patients with advanced HIV between 2000–2003 (95.2%) and 2004–2007 (76.7%), and although variable, this percentage tended to be lower more recently (P-trend = 0.006). One hundred and fifty (71.8%) patients had an ART start date and/or were assumed to be on ART, and this was relatively stable over the study period with no evidence of a linear trend (P-trend = 0.78). Median duration of ART receipt among patients with an ART start date was 74 months [IQR 21–168] overall, and there was strong evidence of an increasing linear trend in the median time interval over the study period with the longest median time interval observed in 2016–2019 at 152 months [IQR 61–223] (P-trend < 0.001) (Table The percentage of those ‘newly diagnosed’ with HIV (i.e. diagnosed with HIV-1 infection within 3 months of ICU admission) was quite variable over the study period, with no evidence of a linear trend, where the highest proportion was observed in 2004–2007 (35.7%) and lowest in 2008–2011 (11.1%)  and 38.5% (85), respectively, with both outcomes declining over the study period ; log2 transformed, per doubling). Patient's age, sex, HIV stage, whether they were receiving ART, respiratory failure and renal failure were not associated with in-ICU mortality. The odds of in-ICU mortality significantly decreased over the 20-year period, with an estimated decrease of 11% per year (cOR: 0.89 (95% CI: 0.84–0.94)). After adjusting for patient demographics and clinical factors, the estimated decreasing trend in in-ICU mortality was attenuated to 3% per year [adjusted OR (aOR): 0.97 (95% CI: 0.90–1.05)] and was no longer statistically significant : 1.15 : 1.10–1.21); per unit increase] and CD4+ T-cell count . Patient's age, sex, HIV stage, whether they were receiving ART, respiratory failure and renal failure were not associated with in-hospital mortality. The odds of in-hospital mortality significantly decreased over the 20-year period, with an estimated decrease of 14% per year [cOR: 0.86 (95% CI: 0.82–0.91)]. After adjusting for patient demographics and clinical factors, the estimated decreasing trend was slightly attenuated to 10% per year [aOR: 0.90 (95% CI: 0.84–0.97)] and remained statistically significant ; per unit increase] and CD4To our knowledge, this is one of very few contemporary, large retrospective studies in a well resourced setting to span a 20-year period of ICU patient care for PWH in the ART era. Our analyses indicate strong evidence of sustained decreases in both in-ICU and in-hospital mortality over the 20-year study period of 11 and 14% per year, respectively, in univariable analyses. After adjustment for patient demographics and clinical factors, the estimated reduction in in-hospital mortality diminished slightly to 10% per year and remained statistically significant. However, the estimated decrease in in-ICU mortality was attenuated and no longer statistically significant, suggesting that the trends seen largely reflect the positive impact on mortality of changes in some of these demographic and clinical factors. The improvement in short-term mortality observed in our study is consistent with trends observed in other studies conducted in the ART era .Pneumocystis jirovecii pneumonia (PCP), bacterial pneumonia and pulmonary tuberculosis, but these events represented a decreasing proportion of the overall ICU caseload, where the proportion of LRTI accounted for by PCP also fell markedly over time. A similar trend was also observed for respiratory failure, which was the most frequently documented organ failure requiring ICU-level support. Changes in both these parameters reflect the progressive increase in diversity of the overall caseload of PWH being admitted to ICU, where AIDS-defining illnesses decreased in proportion over time, while the frequency of exacerbations of co-morbidities, malignancy-related complications, surgical admissions and diagnoses unrelated to HIV, increased. Whilst historically, the association of respiratory failure with in-ICU and in-hospital mortality in PWH has been well established, this finding is less prevalent in more recent studies [The overall decrease in median APACHE II score over time suggests a reduction in severity of illness at the point of ICU admission. The primary medical diagnosis for ICU admission was LRTI (30.3%), which was mainly due to  studies –11,18–20 studies ,13,26,33The recognition and management of sepsis has also improved markedly over the study period, since the inception of the Surviving Sepsis campaign in 2002 to the latest iteration of sepsis management guidelines, which emphasize the importance of prompt delivery of effective antimicrobial therapy, intravenous fluid resuscitation, monitoring of vital signs and early escalation of patients in septic shock to higher level care where needed ,27. This+ T-cell count, and thus, a lower proportion of patients with CD4+ T-cell count <200 cells/μl. The proportion of PWH receiving ART has markedly increased, influenced by a drive to achieve the UNAIDS 90–90–90 target as well as the paradigm shift brought about by the recommendation of universal treatment for all PWH in 2014 [The trend of both reducing severity of acute illness and state of immunosuppression can also be explained in part by advances in the clinical management of HIV-1 infection. Our findings demonstrate an increase in the number of patients admitted to the ICU who were virally suppressed on ART, and a reduction in HIV-related immunosuppression over time, consistent with previous studies. This was reflected by a greater proportion of patients with an undetectable viral load in later years, as well as a higher median CD4 in 2014 ,39. The  in 2014 ,19.+ T-cell count <350 cells/μl or having an AIDS-defining illness regardless of CD4+ T-cell count at the time of HIV diagnosis, has been shown to be associated with increased short-term mortality due to a higher incidence of advanced HIV-related events, and is an acknowledged risk factor for in-ICU mortality [Late HIV diagnosis, defined as CD4ortality –46. We hortality . This haWe acknowledge several limitations to our study. First, this was a single-centre, retrospective study in an HIV-referral centre in central London, which limits our ability to generalize our findings. Second, the retrospective nature of our study meant that we encountered incomplete data collection from patient records from the early part of the study. We were unable to capture the ethnicity and the risk factor for HIV acquisition for study participants. Unfortunately these data were not routinely captured for the majority of the study period by National Health Service hospitals including our own, though UK data suggest this is improving over time . Third, Future research regarding ICU outcomes for PWH who are admitted to ICU should include prospective validation of the APACHE II, III and IV scores in the era of ART. Further, while short-term outcomes from ICU admission are well described, there is a paucity of literature on longer-term outcomes; for example, at one year. Finally, studies should directly compare short-term and long-term outcomes in PWH with outcomes in the HIV-uninfected general population.In conclusion, we describe improving short-term outcomes including in-ICU and in-hospital mortality, in PWH admitted to ICU over a 20-year study period. This may be due to factors including advances in critical care, decreasing trends in severity of acute illness and decreasing levels of HIV-related immunosuppression observed over time.The authors are grateful for the contributions of the Royal Free ICU Data Management Team including Dr Mark de Neef, Dr Nazri Unni and Peggy Tsang. The authors are also grateful for the contributions of the HIV Data Management Team, led by Alan Hunter.Author contributions: R.F.M., B.A. and C.S. conceptualized the study. T.K., M.S., O.D., S.R. and R.F.M. curated the database. N.B. performed the statistical analyses under the supervision of C.S. T.K., N.B., C.S. and R.F.M. analysed the data, with critical input from O.D., M.S., S.R., A.A., M.C.L., S.B. and B.A. T.K., N.B., C.S. and R.F.M. wrote the first draft of the manuscript. All authors contributed to writing of subsequent drafts and reviewed and approved the final manuscript. T.K. and R.F.M. verified the underlying data and jointly act as guarantors.Funding disclosure: There was no funding received for this work to discloseThere are no conflicts of interest.Meetings: Limited, preliminary data from this study were presented at the British HIV Association Conference, Manchester, UK (19–21 April 2022): Abstract O07.


Suppressed patients with drug-resistant HIV-1 require effective and simple antiretroviral therapy to maintain treatment adherence and viral suppression.This randomized, open-label, noninferiority, multicenter pilot study involved HIV-infected adults who met the following criteria: confirmed HIV-1 RNA <50 copies/mL for ≥6 months preceding the study randomization, treatment with at least 3 antiretroviral drugs, and a history of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to darunavir (DRV) and integrase inhibitors. Participants were randomized 1:1 to switch to dolutegravir  plus DRV boosted with cobicistat  or continue with their baseline regimen (standard-of-care [SOC] group). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at week 48 relative to time to loss of virologic response, with a noninferiority margin set at −12.5%. Virologic failure was defined as confirmed HIV-1 RNA ≥50 copies/mL or a single determination of HIV-1 RNA >50 copies/mL followed by antiretroviral therapy discontinuation.P = .159) with an estimated difference of −8.7 . Only 2 (4.5%) in the SOC group experienced virologic failure, and 3 participants from the 2D group experienced adverse events leading to treatment discontinuation.Forty-five participants were assigned to the 2D group and 44 to the SOC group. Time to loss of virologic response showed no difference in the proportion maintaining HIV-1 RNA <50 copies/mL at week 48: 39 of 45  in the 2D group vs 42 of 44  in the SOC group . Simple, effective, and well-tolerated antiretroviral therapy (ART) combinations are needed to maintain lifelong HIV-1 suppression in patients with high therapeutic experience and multidrug resistant HIV-1. These individuals often achieve virus suppression through complex ART combinations, which are difficult to maintain in the long run due to pill fatigue and poor treatment adherence. Dual ART based on boosted protease inhibitors plus integrase strand transfer inhibitors (INSTIs) has been evaluated in clinical trials as a second-line salvage strategy in those with HIV harboring drug resistance mutations (DRMs) [Darunavir (DRV) boosted with ritonavir (DRV/r) or cobicistat (DRV/c) and dolutegravir (DTG) can be given once daily, are well tolerated, and have a high genetic barrier to resistance. DRV and DTG have demonstrated antiviral efficacy in patients with limited therapeutic options .DTG's major and minor metabolic pathways are UDP-glucuronosyltransferase 1A1 and cytochrome 3A4, respectively. Since ritonavir is a UDP-glucuronosyltransferase inducer, coadministration of DTG with ritonavir can decrease trough concentrations of DTG by nearly 40%, which may lead to inappropriately low concentrations of DTG in some patients. By contrast, cobicistat does not induce glucuronidation , and DTGHere, we evaluated the efficacy and safety of DTG plus DRV/c as a once-daily maintenance strategy vs continuing the previous ART in patients who were highly treatment experienced with HIV-1 resistant to drugs but not INSTIs or DRV.This was an open-label, randomized, noninferiority, and multicenter pilot clinical trial to evaluate the efficacy of DTG plus DRV/c as a once-daily simplification strategy as compared with the continuation of the current ART in maintaining virologic suppression (RNA HIV-1 <50 copies/mL) in participants who were highly ART experienced and harboring archived DRM against at least 2 antiretroviral classes.Study participants were randomized 1:1 to receive dual therapy based on DTG (50 mg) plus DRV/c (800/150 mg) once daily (the 2D arm) or a continuation of their current stable and standard-of-care (SOC) ART (the control arm). The randomization list was created by using a uniform distribution and assigning a range of values to each group. The assignment was made by REDCap's randomization module. The study duration was 52 weeks, which included a 4-week screening period plus a 48-week follow-up period.The study was approved by the Ethics Committee of the Hospital Universitari Germans Trias i Pujol (AC-18-074-HGT-CEIM) and by the Spanish Regulatory Authorities, and it was conducted according to the stipulations of the Declaration of Helsinki  and local personal data protection law (LOPD 15/1999). All patients provided their written informed consent for participation. The study is registered at ClinicalTrials.gov (NCT03683524).https://hivdb.stanford.edu). However, their virus had to remain fully susceptible to DRV (Stanford DB score <15) and lack all the following INSTI-associated DRMs: T66A/I/K, L74M, E92G/Q, G118R, T97A, F121Y, E138A/K/T, G140A/C/S, Y143A/C/G/R/H/S, S147G, Q148H/K/R, N155H, S230R, and R263K. Participants were considered not eligible if they had a history of poor adherence or virologic failure while receiving integrase inhibitors; had concomitant treatments with potential drug interactions with DRV/c or DTG; were hepatitis B surface antigen positive; or had unstable liver disease, severe hepatic impairment (Child-Pugh class C), or hepatitis C coinfection that would require therapy during the study.Eligible participants were HIV-infected adults treated with at least 3 antiretroviral drugs  and with confirmation of suppressed HIV-1 RNA <50 copies/mL during at least 6 months preceding randomization. Patients had to have historical genotypic evidence of DRM against ≥2 antiretroviral classes according to the Stanford DB . Secondary endpoints included the proportion of participants with HIV-1 RNA <50 copies/mL at week 48 per the Food and Drug Administration (FDA) snapshot algorithm; the percentage developing ART-associated adverse events leading to treatment discontinuation; changes in CD4g for 15 minutes) and stored at −20 °C until analysis. DTG and DRV concentrations in plasma were determined with ultrahigh-performance liquid chromatography with tandem mass spectrometry according to a validated method [ART adherence was calculated as follows: (number of capsules taken / number of capsules prescribed) × 100. Concentrations of DTG and DRV/c in plasma were determined at week 4 in all patients from the 2D arm and in participants experiencing virologic failure. To this end, blood samples for DTG, DRV, and cobicistat were collected in 5-mL tubes containing potassium and EDTA. Plasma was isolated by centrifugation  in the group treated with DTG plus DRV/c and in the SOC arm with a noninferiority limit of −12.5%. A final sample size of 102 participants (51 per arm) was planned to account for a 5% discontinuation rate during the study follow-up. However, patient inclusion had to be stopped after 109 weeks because there were no more eligible patients in the participating centers. There were no more eligible patients mainly because of participation in other clinical and observational studies, treatment with dual therapies different from the one being studied, the presence of mutations in the protease conferring resistance to DRV (≥15 points according to the Stanford DB), genotypic confirmation or suspicion of resistance to integrase inhibitors, and finally the onset of the SARS-CoV-2 pandemic.Virologic failure was defined as detection of HIV-1 RNA ≥50 copies/mL at 2 consecutive visits measured within 2 to 4 weeks or as a single determination of HIV-1 RNA ≥50 copies/mL followed by premature treatment discontinuation. A genotyping test was performed at virologic failure confirmation. If adverse events resulted in treatment discontinuation or dropout, they were treated as virologic failure for efficacy assessment. The Kaplan-Meier estimation was used to describe TLOVR analysis for all participants and by treatment arm.t test, nonpaired, or paired) or nonparametric tests  were used to compare continuous variables, depending on their distribution and the nature of the comparison (paired or independent).Data from archived genotyping tests, viral tropism, and previous exposure to antiretroviral drugs were collected from electronic history records in the different participating centers. Demographics and clinical parameters were summarized with mean (SD), median (IQR), or frequency (percentage), as appropriate. Frequency distributions for categorical variables were compared with chi-square or Fisher exact tests. Parametric tests (Z statistic for the difference (DTG plus DRV/c – SOC) of the proportion of participants with HIV-1 RNA <50 copies/mL, and its 95% CI was calculated. Noninferiority was concluded if the upper limit of the 2-sided 95% CI was <−12.5%.For the primary efficacy analysis, the noninferiority hypothesis test was based on a 2-sided 95% CI computed with a continuity-corrected The proportion with HIV-1 RNA <50 copies/mL at week 48 according to the FDA snapshot was evaluated. In the FDA snapshot analysis, participants were classified according to 3 outcomes: Responders: HIV-1 RNA <50 copies/mL at week 48 Nonresponders: HIV-1 RNA ≥50 copies/mL at week 48—participants with virologic failure or blips (in window) or participants who discontinued the study drug because of adverse events, death, or other reasons before week 48 with last available HIV-1 RNA ≥50 copies/mL No virologic data: participants who discontinued the study drug before week 48 for reasons other than low efficacy, including adverse event and death with last available HIV-1 RNA <50 copies/mL, and participants who were still taking the study drug but for whom HIV-1 RNA data were missing at week 48P value of the snapshot analysis were calculated by a dichotomized response: HIV-1 RNA <50 copies/mL at week 48 vs HIV-1 RNA ≥50 copies/mL and no virologic data at week 48.The difference in response rates and P < .05.Statistical analysis was performed with SPSS version 15.0 (IBM) and R . Differences were considered statistically significant at Between December 2018 and January 2021, 96 participants were randomized from 12 HIV care centers across Spain. One individual in each group withdrew his or her informed consent before baseline. In addition, 3 participants in the 2D group and 2 in the SOC group were excluded before baseline due to protocol violation. These 7 patients did not receive the study treatment. Therefore, the efficacy analysis set and safety analysis set included 89 participants: 45 in the 2D group and 44 in the SOC group .Demographics and clinical characteristics were well balanced between groups at baseline . The medP = .159). The estimated difference in the proportion of virologic failure between the experimental group and the control was −8.7 . Noninferiority could not be demonstrated, as the upper confidence interval of the difference exceeds the noninferiority limit of −12.5%. Similarly, the FDA snapshot analysis (n = 89) showed no differences in the proportion of patients maintaining virologic suppression in both arms (P = .147). Three (6.7%) and 5 (11.4%) participants in the 2D and SOC groups, respectively, experienced blips during the follow-up period (P = .480).No virologic failures occurred in the 2D group. In contrast, 2 (4.5%) met the criteria for confirmed virologic failure at weeks 12 and 24 in the SOC group. Information about the 2 participants who experienced virologic failure is detailed in the P = .334). The median (IQR) change from baseline in CD4+ cell count at week 48 was −1.0 cells/mm3 (−2.9 to 0.5) in the 2D arm and 0.4 cells/mm3 (−2.7 to 2.8) in the SOC arm (P = .130). Regarding the lipid profile, the median change in total cholesterol from baseline was −0.8 mg/dL (−19.3 to 26.0) in the 2D group and 3.00 mg/dL (−10.0 to 15.5) in the SOC group (P = .970).There were no differences between groups in mean ART adherence at 48 weeks , respectively. Triglyceride levels did not show significant changes, with a median change of −7.0 mg/dL (−35.3 to 60.0) in the 2D group and 10.0 mg/dL (−17.3 to 40.6) in the SOC group (P = .570). In addition, the number of patients taking lipid-lowering drugs increased from 12 to 13 in the 2D group and from 14 to 16 in the SOC group. Similarly, creatinine plasma levels and estimated glomerular filtration rate remained stable during the study period without significant differences between groups (Median changes in low- and high-density lipoprotein cholesterol were 0.0 mg/dL (−26.6 to 24.0) and −1.1 mg/dL (−6.4 to 4.4) in the 2D group and −2.3 mg/dL (−19.0 to 16.0) and −2.0 mg/dL (−5.4 to 2.8) in the SOC group (n groups .P = .002) were documented  of 45 patients in 2D group and 32 (72.7%) of 44 in SOC group had at least 1 adverse event. A total of 111 adverse events in the 2D arm and 81 in the SOC arm  [50 for wild type HIV in all but 1 case [Trough concentrations (20–28 hours after dosing) in plasma were available for all 45 selected participants allocated to the 2D arm . Mean (Stration)  in all ct 1 case . No adheThis study shows that dual therapy with DRV/c plus DTG maintains viral suppression in patients who are well suppressed, adherent to ART, and highly experienced and are harboring archived DRM against at least 2 antiretroviral classes but fully active DRV and INSTIs. This regimen may be a valid option for simplifying ART in highly experienced patients with suppressive but complex ART regimens that could cause pill fatigue and adherence concerns, as well as individuals taking drugs that may have reduced long-term effectiveness due to the presence of archived DRMs, regardless of the regimen's complexity.In our study, there were no significant differences in virologic efficacy in the TLOVR or FDA snapshot analyses. While there were 2 virologic failures in the SOC arm, none was observed in the 2D arm. This is consistent with previous studies of protease inhibitors plus integrase inhibitors or lamivudine as first-line or simplification therapy , 15. UnlThe efficacy of DTG and DRV has been well demonstrated in randomized clinical trials in early and advanced salvage ART, as well as a simplification in highly experienced patients harboring DRM , 17. UntBefore randomization, 57% and 76% of the 2D arm and SOC arm were taking integrase inhibitors, respectively. In addition, 71% of patients in the SOC group were undergoing treatment with protease inhibitors, mainly DRV, while 73% of patients in the 2D group were taking boosted DRV before randomization. This could be the main reason why we did not observe significant differences between groups in the fasting lipid profile, plasmatic creatinine levels, and glomerular filtration rate, despite the use of cobicistat and DTG. Additionally, no additive effect was observed in these renal parameters due to the combined use of DTG and cobicistat in the same regimen, nor were any cases observed of dual-therapy discontinuation for worsening renal function or in the fasting lipid profile. These findings are concordant with clinical and observational studies in which DTG and DRV/c individually or in combination have been shown to be safe and well tolerated , 22.There were a high proportions of participants taking boosted DRV and INSTIs before randomization in the 2D group, including 44% with DRV/c, 29% with DRV/r, and 38% with DTG. Notably, there were more overall and drug-related adverse events in the 2D group, although they were mainly grade I and II. These safety results, however, should be interpreted with caution due to the open label design. Yet, they are not surprising, since the change to a new treatment regimen is usually associated with a higher risk of experiencing adverse events or tolerance problems. Nonetheless, it is worth noting that adverse events leading to treatment discontinuation were infrequent. Only 3 participants undergoing dual therapy with DTG plus DRV/c discontinued their ART due to arthralgia, diarrhea, and rash. In these cases, the switch to DRV/c plus DTG involved some ART changes. The patient experiencing arthralgia started both drugs for the first time. In the case of the one who discontinued due to diarrhea, ritonavir was replaced with cobicistat as the booster for DRV. For the individual who experienced rash, abacavir/lamivudine was substituted with DTG. These are well-known adverse events related to these drugs , and une90 for DTG [50 for DRV [Our study has a number of limitations. The enrolment of patients had to be stopped due to the lack of eligible participants. Therefore, the study was underpowered to detect 90% efficacy and demonstrate the noninferiority of DTG plus DRV/c dual therapy vs maintenance of ART. In addition, the study may have introduced selection biases based on its open design and the fact that good ART adherence prior to study initiation was assumed but not measured; as such, safety and efficacy results must be interpreted with caution. Nevertheless, to our knowledge, this is the first randomized study to compare a dual therapy made up of DTG and DRV/c as a simplification strategy in patients infected with HIV who had high ART experience and resistance to at least 2 classes of antiretroviral drugs but with DTG and DRV still fully active. In addition, the study provides some insights into the main safety and pharmacokinetic issues. Similar to observations in healthy volunteers , our dat for DTG  and IC50 for DRV  in all p for DRV .In summary, while noninferiority could not be demonstrated and no specific advantage in terms of tolerance was observed, dual therapy with DTG plus DRV/c appeared to be a safe approach. It may maintain viral suppression without the development of virologic failures or unexpected adverse events in patients highly experienced with resistance to at least 2 antiretroviral classes, as long as they retain DRV- and INSTI-susceptible HIV-1. To minimize the risk of virologic failure, proper selection of candidates for simplification with this once-daily strategy is mandatory.Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.ofad542_Supplementary_DataClick here for additional data file.