Immunological and virological response to fostemsavir in routine US clinical care: An OPERA cohort study.

OBJECTIVES: Fostemsavir is a novel attachment inhibitor used with other antiretrovirals in heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. Real-world immunological and virological responses were assessed in individuals starting fostemsavir in the OPERA cohort. METHODS: Among adults with HIV-1 starting fostemsavir between 2 July 2020 and 1 September 2022, 6-month and 12-month changes in CD4 T-cell count and CD4%, and maintenance/achievement of viral load (VL) <50 copies/mL were described and stratified by baseline VL (suppressed: <50 copies/mL; viraemic: ≥50 copies/mL) and CD4 count (high: ≥350 cells/µL; low: <350 cells/µL). RESULTS: Of 182 individuals starting fostemsavir, 64% were viraemic (34% low CD4, 30% high CD4) and 36% were suppressed (16% low CD4, 20% high CD4). The suppressed/low CD4 group had the largest median increases in CD4 count (6-month: 30 cells/µL [interquartile range {IQR} 9-66], 12-month: 66 cells/µL [IQR 17-125]), and CD4% (6-month: 1.0% [IQR -0.3-2.8], 12-month: 1.9% [IQR 1.3-3.9]). Regardless of baseline VL, those with a high baseline CD4 count experienced a greater variability in immunological response than those with low CD4 counts (12-month standard deviation range 172-231 cells/µL vs. 69-90 cells/µL). VL <50 copies/mL was maintained in most suppressed individuals; nearly half of the viraemic/high CD4 group and a third of the viraemic/low CD4 group achieved a VL <50 copies/mL at either timepoint. CONCLUSIONS: After 6 or 12 months of fostemsavir use, virological response was low in viraemic individuals, although most suppressed individuals did maintain suppression. While immunological response varied across individuals, virologically suppressed HTE individuals with low CD4 counts may benefit from immunological improvements with fostemsavir.

Immune response to ART initiation in advanced HIV infection.

OBJECTIVES: Our objective was to compare the immunological responses to commonly used antiretroviral therapy (ART) regimens among people with advanced HIV in the USA and to assess virological outcomes and regimen persistence. METHODS: This study included ART-naïve adults with advanced HIV infection (CD4 cell count <200 cells/µL) initiating ART with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), boosted darunavir (bDRV), dolutegravir (DTG), or elvitegravir (EVG/c)-containing regimens between 1 January 2018 and 31 December 2020 in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. Cox proportional hazards models and linear mixed models with random intercept were fit with inverse probability of treatment weighting. RESULTS: Overall, 1349 people with advanced HIV (816 B/F/TAF, 253 DTG, 146 EVG/c, 134 bDRV) were followed for a median of 22 months. Compared with B/F/TAF, a lower likelihood of achieving a CD4 cell count ≥200 cells/µL was observed with bDRV (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.60-0.96), DTG (HR 0.82; 95% CI 0.69-0.98), and EVG/c (HR 0.73; 95% CI 0.57-0.93). All groups had a similar pattern of CD4:CD8 ratio changes: a rapid increase in the first 6 months (ranging from +0.15 to +0.16 units), followed by a slower increase thereafter. Only 40 individuals (4%) achieved CD4:CD8 ratio normalization (≥1). B/F/TAF was associated with a faster time to virological suppression (viral load <200 copies/mL) and a slower time to discontinuation compared with other regimens. CONCLUSIONS: Among people with advanced HIV infection, B/F/TAF initiation was associated with faster CD4 cell count recovery and favourable virological outcomes compared with bDRV-, DTG-, and EVG/c-based regimens, although no difference was observed in CD4:CD8 ratio changes over time across regimens.

Heavily treatment-experienced people living with HIV in the OPERA® cohort: population characteristics and clinical outcomes.

BACKGROUND: Multi-class resistance, intolerance, and drug-drug interactions can result in unique antiretroviral (ART) combinations for heavily treatment-experienced (HTE) people living with HIV (PLWH). We aimed to compare clinical outcomes between HTE and non-HTE PLWH. METHODS: Eligible ART-experienced PLWH in care in the OPERA® Cohort were identified in a cross-sectional manner on December 31, 2016 and observed from the date of initiation of the ART regimen taken on December 31, 2016 until loss to follow up, death, study end (December 31, 2018), or becoming HTE (non-HTE group only). In the absence of resistance data, HTE was defined based on the ART regimens used (i.e., exposed to ≥ 3 core agent classes or regimen suggestive of HTE). Time to virologic undetectability, failure, and immunologic preservation were assessed using Kaplan-Meier methods; cumulative probabilities were compared between the two groups. Regimen changes, incident morbidities, and death were described. RESULTS: A total of 24,183 PLWH (2277 HTE PLWH, 21,906 non-HTE) were followed for a median of 28 months (IQR 21, 38). Viremic HTE PLWH (viral load [VL] ≥ 50 copies/mL) were less likely to achieve undetectability (VL < 50 copies/mL; 24-month cumulative probability: 80% [95% Confidence Interval 77-82]) than their non-HTE counterparts (85% [84-86]). No difference was observed in the probability of maintaining VLs < 200 copies/mL over the first 48 months after achieving suppression (< 50 copies/mL). HTE PLWH were less likely than non-HTE PLWH to maintain CD4 cell counts ≥ 200 cells/µL (24-month cumulative probability: 95% HTE [91-93]; 97% non-HTE [97-97]), and more likely to change regimens (45% HTE; 41% non-HTE). Incident non-AIDS defining event (ADE) morbidities were common in both populations, though more likely among HTE PLWH (45%) than non-HTE PLWH (35%). Incident ADE morbidities and deaths were uncommon among HTE (ADEs 5%; deaths 2%) and non-HTE (ADEs 2%; deaths 1%) PLWH. CONCLUSIONS: HTE PLWH were at greater risk of unfavorable treatment outcomes than non-HTE PLWH, suggesting additional therapeutic options are needed for this vulnerable population.

HLA-B*57:01 screening and hypersensitivity reaction to abacavir between 1999 and 2016 in the OPERA® observational database: a cohort study.

BACKGROUND: HLA-B*57:01 screening was added to clinical care guidelines in 2008 to reduce the risk of hypersensitivity reaction from abacavir. The uptake of HLA-B*57:01 screening and incidence of hypersensitivity reaction were assessed in a prospective clinical cohort in the United States to evaluate the effectiveness of this intervention. METHODS: We included all patients initiating an abacavir-containing regimen for the first time in the pre-HLA-B*57:01 screening period (January 1, 1999 to June 14, 2008) or the post-HLA-B*57:01 screening period (June 15, 2008 to January 1, 2016). Yearly incidence of both HLA-B*57:01 screening and physician panel-adjudicated hypersensitivity reactions were calculated and compared. RESULTS: Of the 9619 patients eligible for the study, 33% initiated abacavir in the pre-screening period and 67% in the post-screening period. Incidence of HLA-B*57:01 screening prior to abacavir initiation increased from 43% in 2009 to 84% in 2015. The incidence of definite or probable hypersensitivity reactions decreased from 1.3% in the pre-screening period to 0.8% in 2009 and further to 0.2% in 2015 in the post-screening period. CONCLUSIONS: Frequency of HLA-B*57:01 screening increased steadily since its first inclusion in treatment guidelines in the United States. This increase in screening was accompanied by a decreasing incidence of definite or probable hypersensitivity reactions over the same period. However, a considerable proportion of patients initiating abacavir were not screened, representing a failed opportunity to prevent hypersensitivity reactions. Where HLA-B*57:01 screening is standard of care, patients should be confirmed negative for this allele before starting abacavir treatment.

Withdrawal of artificial nutrition and hydration in neonatal intensive care: parents' and healthcare practitioners' views.

Withdrawing Artificial Nutrition and Hydration (WANH) in the neonatal intensive care units (NICUs) has long been controversial. In France, the practice has become a legal option since 2005. But even though, the question remains as to what the stakeholders' experience is, and whether they consider it ethically appropriate. In order to contribute to the debate, we initiated a study in 2009 to evaluate parental and health care professionals (HCP) perspectives, after they experienced WAHN for a newborn. The study included 25 cases from 5 different clinical neonatology departments. We interviewed both the parents and some of the HCP who cared for the baby, at least 6 months after this latter deceased. We proceeded through in-depth individual qualitative interviews. Content was analyzed for themes and patterns that emerged from the data. Some parents expressed that WANH offered an opportunity to the family to spend a few demedicalized days with the baby before she dies, without any tubes and machines, and to be well supported by the HCP during this palliative stage. But others evaluated the practice in retrospect as a terrible ordeal. All said that, at least, the time of waiting for death to ensue should not last too long. After a few days, it becomes unbearable because of the transformation of the baby's appearance and because they, as parents, began to wonder if she was not dying from starvation rather than from her initial disease. An important proportion of HCP also expressed some kind of ethical unease. This was due to the psychological violence involved in the decision for a human being to stop feeding a little one, and also to the difficulty to deal with the fundamental intention behind the decision of WANH: indeed, could it be claim that it does not presuppose the intention of provoking the infant's death? The discussion focuses on the point to know if WANH can be considered as a source of progress from an ethical point of view, particularly in comparison with earlier practices-that in France could involve active euthanasia by lethal injection. We argue that when HCP are merely focused on avoiding that WAHN could be construed as a way of intending to hasten the baby's death, the practice is at risk to be implemented in a way that becomes ethically counterproductive. Focusing on this intention easily distract the clinical teams from what should be their ultimate concern, namely the baby's comfort during the dying process, as well as the support owned to her parents. To conclude, we suggest that the ethical priorities, when WANH is decided, should be the support due to the patient and her family on the one hand, and, on the other hand to implement it in such a way that at least the baby seems to have died of her initial disease and never of starvation. This means that HCP have a duty to control the timing of death, even though this might be incompatible with the worry to avoid the intention of hastening the baby's death.

Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C-Coinfected Persons.

BACKGROUND: Liver diseases progress faster in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV-coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). METHODS: Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction-positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. RESULTS: A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, -3%, 19%) or NNRTI users (3% per 5 years, 95% CI, -7%, 12%). CONCLUSIONS: Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV-coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used.

The "Commitment Model" for Clinical Ethics Consultations: Society's Involvement in the Solution of Individual Cases.

Several approaches to clinical ethics consultation (CEC) exist in medical practice and are widely discussed in the clinical ethics literature; different models of CECs are classified according to their methods, goals, and consultant's attitude. Although the "facilitation" model has been endorsed by the American Society for Bioethics and Humanities (ASBH) and is described in an influential manual, alternative approaches, such as advocacy, moral expertise, mediation, and engagement are practiced and defended in the clinical ethics field. Our Clinical Ethics Center in Paris was founded in 2002 in the wake of the Patients' Rights Act, and to date it is the largest center that provides consultation services in France. In this article we shall describe and defend our own approach to clinical ethics consultation, which we call the "Commitment Model," in comparison with other existing models. Indeed commitment implies, among other meanings, continuity through time, a series of coherent actions, and the realization of important social goals. By drawing on a recent consultation case, we shall describe the main steps of our consultation procedure: interviews with major stakeholders, including patients and proxies; case conferences; and follow up. We shall show why we have chosen the term "commitment" to represent our approach at three different but interrelated levels: commitment towards patients, within the case conference group, and towards society as a whole.

The French bioethics public consultation and the anonymity doctrine: empirical ethics and normative assumptions.

The French bioethics laws of 1994 contain the principles of the anonymity and non commodification of all donations of body parts and products including gametes in medically assisted reproduction. The two revisions of the law, in 2004 and 2011 have upheld the rule. In view of the latest revision process, the French government organized a large public consultation in 2009 ("Etats généraux de la bioéthique"). Within the event a "consensus conference" was held in Rennes about different aspects of assisted reproduction (access, anonymity, gratuity and surrogacy). In what follows we shall first describe the anonymity clause for gamete donations in the French law and the debates surrounding it. We shall then analyse the procedure used for the 2009 public consultation and the related consensus conference, as well as its upshot concerning the anonymity doctrine. In this respect we shall compare the citizens' own recommendations on the gamete anonymity issue and its translation in the consultation's final report drafted by a philosopher mandated by the organizing committee. Whereas the final report cited some fundamental ethical arguments as reason for upholding the provisions of the law-most notably the refusal of the 'all biological' approach to reproductive issues-citizens were more careful and tentative in their position although they also concluded that for pragmatic reasons the anonymity rule should continue to hold. We shall argue that the conservative upshot of the public consultation is due to some main underlying presuppositions concerning the citizens' role and expertise as well as to the specific design of the consensus conference. Our conclusion will be that public consultations and consensus conferences can only serve as an empirical support for devising suitable bioethics norms by using second-order normative assumptions.

Personal identity as a form of freedom.

A commentary on "The Ethics of Anonymous Gamete Donation: Is There a Right to Know One's Genetic Origins?" by Inmaculada de Melo-Martín, in the March-April 2014 issue.

Improving Adherence to the Target Window for Cabotegravir + Rilpivirine Long-Acting Injections Through the CHORUS™ App and Web Portal: A Cluster Randomized Trial.

BACKGROUND: We evaluated the impact of the CHORUS™ app on adherence to the cabotegravir and rilpivirine long-acting injectable (CAB + RPV LAI) monthly injections schedule. METHODS: Healthcare centers (HCCs) were randomized to access CHORUS™ CAB + RPV LAI features (intervention) or not (control) from 01OCT2021-31JAN2022. Target window adherence (maintenance injections ≤7 days before/after target day) was assessed with multivariate logistic regression (generalized estimating equations). RESULTS: CAB + RPV LAI was administered to 188 and 79 individuals at intervention and control HCCs, respectively. Intervention was not associated with improved target window adherence (adjusted odds ratio: 0.61 [95% CI: 0.30-1.25]). However, app use was associated with increased odds of adherence compared to no app use among all intervention HCCs (2.98 [1.26-7.06]) and at smaller HCCs (3.58 [1.31-9.80]). CONCLUSIONS: While access to CHORUS™ CAB + RPV LAI features did not improve target window adherence, app use did, especially at smaller HCCs which may not have established LAI management procedures. TRIAL REGISTRATION: https://clinicaltrials.gov/show/NCT04863261.

Evaluation of a mobile app and web portal to help with the timely injections of cabotegravir + rilpivirine long-acting injectionsCabotegravir + rilpivirine long-acting injectable (CAB+RPV LAI) is the first long-acting regimen for HIV treatment, which was approved in the US in 2021. CAB+RPV LAI should be administered ≤7 days before/after the target date. We conducted a trial to evaluate the impact of the CHORUS™ app and web portal on the timing of monthly CAB+RPV injections. The intervention clinics had access to features designed to help with CAB+RPV LAI management, including flagging delayed/missed injections and appointment scheduling status. Control clinics did not have access to these features and managed CAB+RPV LAI administration on their own. Access to the app and web portal features for intervention clinics had no impact on timing of injections compared to control clinics. However, intervention clinics who actively used the app were close to three times more likely to give injections on-time than intervention clinics who did not use the app. The effect of app use was seen specifically among smaller clinics caring for <1000 people with HIV: smaller clinics that actively used the app were 3.58 times more likely to give injections on-time than those who did not use the app. In conclusion, while access to CHORUS™ CAB+RPV LAI features in the app and the web portal did not improve the likelihood of on time injections, actively using the app did make a difference, especially at smaller clinics which may not have established injection management procedures.

Switching to Dolutegravir/Lamivudine Two-Drug Regimen: Durability and Virologic Outcomes by Age, Sex, and Race in Routine US Clinical Care.

Purpose: Two-drug regimens (2DR) may address drug-drug interactions and toxicity concerns. Dolutegravir/lamivudine (DTG/3TC) 2DR was approved in the US for both treatment-naïve and treatment-experienced individuals with a viral load <50 copies/mL. This study describes real-world DTG/3TC 2DR treatment outcomes among treatment-experienced individuals, stratified by age, sex, and race. Methods: From the OPERA® cohort, people with HIV with a viral load <50 copies/mL who switched from a commonly used three-drug regimen to DTG/3TC 2DR as per the label between April 8, 2019 and April 30, 2021 were included. Incidence rates (Poisson regression) for loss of virologic control (first viral load ≥50 copies/mL), confirmed virologic failure (2 viral loads ≥200 copies/mL or discontinuation after 1 viral load ≥200 copies/mL), and DTG/3TC 2DR discontinuation were estimated overall and stratified by age, sex, and race. Results: The 787 individuals included were followed for a median of 13.6 months (IQR: 8.2, 22.3). Confirmed virologic failure occurred in ≤5 individuals. Loss of virologic control occurred at a rate of 14.0 per 100 person-years (95% CI: 11.7, 16.8). DTG/3TC 2DR discontinuation occurred at a rate of 17.5 per 100 person-years (95% CI: 15.0, 20.3); 4% discontinued for treatment-related reasons (viremia, adverse diagnosis, side effect, lab abnormality). For all outcomes, incidence rates were comparable across strata of age, sex, and race. Conclusion: This descriptive study demonstrates that DTG/3TC 2DR is an effective and well-tolerated treatment option for people with HIV with a viral load <50 copies/mL at switch, regardless of their age, sex, or race.

Incident HIV-Associated Wasting/Low Weight Is Associated with Nearly Doubled Mortality Risk in the Modern ART Era.

HIV-associated wasting (HIVAW) is an underappreciated AIDS-defining illness, despite highly effective antiretroviral therapy (ART). We (a) assessed the association between incident HIVAW/low weight and all-cause mortality and (b) described virologic outcomes after people with HIV (PWH) experienced HIVAW/low weight while on ART. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort, PWH without prior HIVAW/low weight who were active in care in 2016-2020 were followed through the first of the following censoring events: death, loss to follow-up, or study end (October 31, 2021). HIVAW/low weight was a diagnosis of wasting or low body mass index (BMI)/underweight or a BMI measurement <20 kg/m2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent HIVAW/low weight and mortality were estimated with extended Cox regression models. Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of HIVAW/low weight and 1,354 (2%) deaths among 62,314 PWH. PWH who experienced HIVAW/low weight had a significantly higher risk of death than those who did not (HR: 1.96; 95% CI: 1.68, 2.27) after adjusting for age, race, ethnicity, and changes in viral load (VL) and Veterans Aging Cohort Study Mortality Index scores over follow-up. Among 4,572 PWH on ART at HIVAW/low weight, 68% were suppressed (VL of <200 copies/mL); subsequent virologic failure was uncommon (7%). Among viremic PWH, 70% and 60% achieved suppression and undetectability (VL of <50 copies/mL), respectively, over follow-up. HIVAW remains a challenge for some PWH. Particular attention needs to be paid to HIVAW/low weight and virologic control to restore health and potentially reduce the risk of death.

[Extension of the Use of Gametes in Intra-Conjugal (EUGIC): How to use trans woman' spermatozoa?] / Extension de l'Utilisation de Gamètes en IntraConjugal (EUGIC): quel usage des spermatozoïdes d'une femme trans?

- Objective: The French Law relating to Bioethics allows access to medically assisted reproduction for lesbian couples and single women and has expanded the possibilities for self-preservation of gametes. The question now arises of new uses of gametes of the couple, within couples of two cis women, one cis woman and one transgender woman, or two transgender individuals. The acronym EUGIC (Extension of the Use of Gametes in IntraCouple) allows these new situations to be grouped together, particularly if gametes have already been previously cryopreserved, thus avoiding the need for gamete donation. - Methods: Analysis of the different situations of sperm use from a trans woman using gametes available within the couple rather than gamete donation. - Results: The inconsistency in the use of sperm from a trans woman, the situations already encountered by professionals, the prospects for filiation for a trans woman as well as the issues related to the interest of the unborn child are discussed. - Conclusion-: French law does not fully address the use of a trans woman's spermatozoa to meet the new EUGIC requirements and leads to complex situations for healthcare professionals.

Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis.

BACKGROUND: Marijuana smoking is common and believed to relieve many symptoms, but daily use has been associated with liver fibrosis in cross-sectional studies. We aimed to estimate the effect of marijuana smoking on liver disease progression in a Canadian prospective multicenter cohort of human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected persons. METHODS: Data were analyzed for 690 HCV polymerase chain reaction positive (PCR-positive) individuals without significant fibrosis or end-stage liver disease (ESLD) at baseline. Time-updated Cox Proportional Hazards models were used to assess the association between the average number of joints smoked/week and progression to significant liver fibrosis (APRI ≥ 1.5), cirrhosis (APRI ≥ 2) or ESLD. RESULTS: At baseline, 53% had smoked marijuana in the past 6 months, consuming a median of 7 joints/week (IQR, 1-21); 40% smoked daily. There was no evidence that marijuana smoking accelerates progression to significant liver fibrosis (APRI ≥ 1.5) or cirrhosis (APRI ≥ 2; hazard ratio [HR]: 1.02 [0.93-1.12] and 0.99 [0.88-1.12], respectively). Each 10 additional joints/week smoked slightly increased the risk of progression to a clinical diagnosis of cirrhosis and ESLD combined (HR, 1.13 [1.01-1.28]). However, when exposure was lagged to 6-12 months before the diagnosis, marijuana was no longer associated with clinical disease progression (HR, 1.10 [0.95-1.26]). CONCLUSIONS: In this prospective analysis we found no evidence for an association between marijuana smoking and significant liver fibrosis progression in HIV/HCV coinfection. A slight increase in the hazard of cirrhosis and ESLD with higher intensity of marijuana smoking was attenuated after lagging marijuana exposure, suggesting that reverse causation due to self-medication could explain previous results.

Gamete donation in France: the future of the anonymity doctrine.

In France, since the approval of the first bioethics laws in 1994, the principle of the anonymity of sperm donors has prevailed. This choice is regularly challenged, namely by children who have been conceived under these conditions and have now reached adulthood. In this paper, we will briefly describe the reasons that led practitioners of assisted reproduction to endorse the anonymity principle in 1994. Secondly, we will elaborate on the reasons why this principle is becoming so controversial today. Finally, we shall examine two possible outcomes of the debate, highlighting their respective legitimacy as well as their consequences, as far as the rights of children, the notion of the family, and medical practice are concerned.

Definition, Burden, and Predictors of HIV-Associated Wasting and Low Weight in the OPERA Cohort.

We aimed to describe the prevalence, incidence, and predictors of HIV-associated wasting (HIVAW)/low weight among people with HIV (PWH) in the United States. We conducted an observational, clinical cohort analysis, utilizing prospectively collected electronic health record data obtained from the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort. HIVAW/low weight included a wasting or low body-mass index (BMI)/underweight diagnosis (ICD codes and title search) or BMI <20 kg/m2. Prevalence was estimated among adult PWH in care from 2012 to 2015 and 2016 to 2020. Incidence from January 1, 2016, to October 31, 2021, was estimated using univariate Poisson regression among eligible PWH without prior HIVAW/low weight. Demographic and clinical predictors of incident HIVAW/low weight were included in multivariable logistic regression models, stratified by antiretroviral therapy (ART) experience. The period prevalence of HIVAW/low weight was 12% in both 2012-2015 and 2016-2020. Among 67,119 PWH without any prior HIVAW/low weight, 7% experienced incident HIVAW/low weight a median 64 months from HIV diagnosis. In multivariable regression models, similar predictor patterns were observed among ART-naïve and ART-experienced PWH without any prior HIVAW/low weight: lower odds of HIVAW/low weight with older age, female sex, Black race, and Hispanic ethnicity and higher odds with Medicaid. Notably, there was a dose-response relationship between increasing Veterans Aging Cohort Study Mortality Index scores and incident HIVAW/low weight in both groups. Wasting/low weight remains a challenge for PWH and may be underappreciated by providers. Advanced HIV and comorbidities significantly predict incident HIVAW/low weight. Increasing awareness of HIVAW, especially among frailer PWH, could improve the care of affected PWH.

Cabotegravir + Rilpivirine Long-Acting Injections for HIV Treatment in the US: Real World Data from the OPERA Cohort.

INTRODUCTION: The first complete long-acting antiretroviral therapy (ART) regimen, cabotegravir + rilpivirine long-acting (CAB + RPV LA) injectable, was approved in the US for HIV-1 treatment in individuals on a stable antiretroviral regimen with a viral load < 50 copies/mL, no treatment failure history, and no resistance to either cabotegravir or rilpivirine. We describe injection schedule adherence and virologic effectiveness of CAB + RPV LA in routine clinical care in the US. METHODS: From the OPERA® cohort, all adults with HIV who received their first CAB + RPV LA injection and ≥ 1 continuation injections between 21 January 2021 and 15 March 2022 were included. The injection target date was updated monthly and set to the same date of the month as the previous injection. Continuation injections administered within 7 days before or after the target date were considered on time, as per the label. Virologic undetectability (viral load < 50 copies/mL), suppression (viral load < 200 copies/mL), and confirmed virologic failure (2 consecutive viral loads ≥ 200 copies/mL or 1 viral load ≥ 200 copies/mL followed by discontinuation) were described among individuals with a viral load < 50 copies/mL at initiation and ≥ 1 follow-up viral load. RESULTS: Among 321 individuals on CAB + RPV LA, 90% of the continuation injections were administered on time (within ± 7 days of the target date). Of the 237 individuals with a viral load < 50 copies/mL at initiation and ≥ 1 follow-up viral load, nearly all were undetectable (95%) or suppressed (99%) at their last viral load measurement, 96% maintained virologic suppression with all measured viral loads < 200 copies/mL, and four confirmed virologic failures were observed. Injection delays were infrequent, and did not affect virologic outcomes over the short term. CONCLUSION: In this large US cohort, most monthly CAB + RPV LA injections were administered on time and high levels of virologic control were achieved. These results suggest that CAB + RPB LA injectable can be administered effectively during routine clinical care.

Excessive Weight Gain: Current Antiretroviral Agents in Virologically Suppressed People with HIV.

An observational cohort study was conducted with data from the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort to investigate weight gain among virologically suppressed people with HIV (PWH) switching to regimens containing tenofovir alafenamide/emtricitabine/(TAF/FTC). Virologically suppressed, antiretroviral therapy (ART)-experienced PWH switching to TAF/FTC with darunavir/cobicistat (DRV/c), elvitegravir/cobicistat (EVG/c), dolutegravir (DTG), or bictegravir (BIC) were selected. Cox proportional hazards models were used to assess the risk of excessive weight gain (i.e., ≥5% gain within 28 weeks or ≥10% within 54 weeks), by regimen. A linear mixed effects model with random intercept and restricted cubic splines on time was used to assess continuous changes in weight. Confounding was controlled for with both inverse probability of treatment weighting and traditional covariate adjustment. Among 5,536 PWH, 18% gained ≥5% of their weight within 28 weeks, and 9% gained ≥10% within 54 weeks. There were no differences in the risk of excessive weight gain by regimen, although there was a nonstatistically significant 20% increase in the risk of gaining ≥10% within 54 weeks with all regimens compared to DRV/c. Throughout follow-up, the mean predicted weight remained fairly constant, with no notable differentiation between regimens. Expected weight gains ranged from +0.2 to +0.3 kg at 6 months and from +0.5 to +0.6 kg at 24 months. In conclusion, in this study of virologically suppressed, ART-experienced PWH switching to regimens containing TAF/FTC and DRV/c, EVG/c, DTG, or BIC, up to 18% experienced excessive levels of weight gain. However, no statistically significant difference was observed across regimens.

Lipid Changes After Switch From TDF to TAF in the OPERA Cohort: LDL Cholesterol and Triglycerides.

BACKGROUND: Increases in lipids have been observed in people with HIV (PWH) switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We assessed changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) following a switch from TDF to TAF. METHODS: Adults with ≥1 lipid measure before and after switch from TDF to TAF were identified in the OPERA cohort. Multivariable linear regression using generalized estimating equations was used to estimate predicted changes in lipids over time on TAF, modeled flexibly with linear splines. RESULTS: A total of 6451 PWH switched from TDF to TAF, of whom 4328 maintained all other agents. LDL-C increased significantly by 1.40 mg/dL/mo over the first 3 months on TAF, by 0.33 mg/dL/mo between 3 and 9 months and then plateauing beyond 9 months. TG increased significantly by 3.52 mg/dL/mo over the first 3 months of TAF, by 0.91 mg/mL/mo between 3 and 9 months and by 0.72 mg/mL/mo between 9 and 16 months, but decreased thereafter. Similar patterns were observed in analyses restricted to PWH who switched from TDF to TAF but maintained all other agents. CONCLUSIONS: TDF-to-TAF switch was associated with LDL-C and TG increases over the first 9 to 16 months on TAF. The dynamic patterns observed cannot be attributed to changes in other agents.

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

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