Roadmap for Achieving Universal Antiretroviral Treatment.

Modern antiretroviral therapy safely, potently, and durably suppresses human immunodeficiency virus (HIV) that, if left untreated, predictably causes acquired immunodeficiency syndrome (AIDS), which has been responsible for tens of millions of deaths globally since it was described in 1981. In one of the most extraordinary medical success stories in modern times, a combination of pioneering basic science, innovative drug development, and ambitious public health programming resulted in access to lifesaving, safe drugs, taken as an oral tablet daily, for most of the world. However, substantial challenges remain in the fields of prevention, timely access to diagnosis, and treatment, especially in pediatric and adolescent patients. As HIV-positive adults age, treating their comorbidities will require understanding the course of different chronic diseases complicated by HIV-related and antiretroviral toxicities and finding potential treatments. Finally, new long-acting antiretrovirals on the horizon promise exciting new options in both the prevention and treatment fields.

Safety Data Timelines for Pregnant Individuals with HIV on Antiretroviral Therapy.

Antiretrovirals are often approved by the Food and Drug Administration without sufficient safety data regarding their use in pregnancy. To quantify this delay, we calculated the interval from the approval date to their inclusion in the Antiretroviral Pregnancy Registry prospective analysis (≥ 200 first trimester exposures); median delay was six years.

Antiretroviral Drug Exposure and Response in Obese and Morbidly Obese People With Human Immunodeficiency Virus (HIV): A Study Combining Modelling and Swiss HIV Cohort Data.

BACKGROUND: Obesity is increasingly prevalent among people with HIV (PWH) and can possibly result in suboptimal antiretroviral drug (ARV) exposure and response. However, this has not been thoroughly evaluated given that obese PWH are underrepresented in clinical trials. We performed virtual trials using physiologically based pharmacokinetic (PBPK) modelling combined with observed clinical data to provide ARV dosing guidance in obese individuals. METHODS: Each trial included a cohort of virtual adults with a body mass index (BMI) between 18.5 and 60 kg/m2. Therapeutic drug-monitoring data from the Swiss HIV Cohort Study (SHCS) were used to verify the predictive performance of the model. Subsequently, the model was applied to predict the pharmacokinetics of ARVs for different obesity classes. The association between ARV plasma concentrations and virological response was investigated in obese and nonobese individuals. RESULTS: The PBPK model predicted an average reduction in ARV exposure of ∼20% and trough concentrations of ∼6% in obese (BMI ≥30 kg/m2) compared with nonobese (BMI: 18.5-25 kg/m2) individuals, consistent with observed clinical data. Etravirine and rilpivirine were the most impacted, especially in individuals with BMI >40 kg/m2 whose trough concentrations were below the clinical target threshold. Obese PWH in the SHCS did not have a higher rate of unsuppressed viral load than nonobese PWH. CONCLUSIONS: The concentrations of ARVs are modestly reduced in obese individuals, with no negative impact on the virological response. Our data provide reassurance that standard doses of ARVs are suitable in obese PWH, including those who gained substantial weight with some of the first-line ARVs.

Comparison of At-Home Versus In-Clinic Receipt of Long-Acting Injectable Cabotegravir/Rilpivirine.

BACKGROUND: The need for frequent travel to a clinic could impair access to injectable antiretroviral therapy for persons living with human immunodeficiency virus type 1 (HIV-1) infection. We hypothesized that allowing persons receiving treatment with long-acting injectable cabotegravir plus rilpivirine (LA CAB/RPV) to receive and store the medication in their own refrigerator prior to in-home administration by a healthcare provider would be as safe and effective as receiving treatment in a clinic. METHODS: Persons prescribed LA CAB/RPV in the Infectious Diseases clinic at the Medical University of South Carolina were offered enrollment in this non-randomized, observational study between August 2021 and December 2022. After in-clinic receipt of the initial LA CAB/RPV injection, participants chose to receive each subsequent injection over the following 12-months either in clinic or at home. RESULTS: The 33 enrolled participants were primarily Black (64%), male (73%), and had a median age of 46. Three participants stopped LA CAB/RPV and transitioned to oral antiretroviral therapy due to allergy (n = 1), loss of virologic suppression (n = 1), and visit adherence (n = 1) concerns. A comparable number of participants received treatment primarily in clinic (n = 18) relative to at home (n = 15). Injection site pain/soreness was common (52% of injections) but did not differ between groups. There were no differences in safety or efficacy between groups and both groups reported high treatment satisfaction. All participants were virologically suppressed and retained in care at the end of the study. CONCLUSIONS: At-home administration of LA CAB/RPV by a healthcare provider was comparably safe, effective, and associated with high participant satisfaction relative to in-clinic administration.

The HIV-1 gag p6: a promising target for therapeutic intervention.

The p6 domain of the Gag precursors (Gag p6) in human immunodeficiency virus type 1 (HIV-1) plays multifunctional roles in the viral life cycle. It utilizes the endosomal sorting complex required for transport (ESCRT) system to facilitate viral budding and release from the plasma membrane through the interactions with the ESCRT-I component tumor susceptibility gene 101 (TSG101) and with the ALG-2 interacting protein X (ALIX). Moreover, Gag p6 contributes to viral replication by a range of posttranslational modifications such as SUMOylation, ubiquitination and phosphorylation. Additionally, Gag p6 also mediates the incorporation of the accessory protein Vpr into virions, thereby promoting Vpr-induced viral replication. However, less attention is focused on Gag p6 as therapeutic intervention. This review focuses on the structures and diverse functions of Gag p6 in viral replication, host cells, and pathogenesis. Additionally, several challenges were also discussed in studying the structure of Gag p6 and its interactions with partners. Consequently, it concludes that the Gag p6 represents an attractive target for the development of antiretroviral drugs, and efforts to develop p6-targeted antiretrovirals are expected to undergo significant growth in the forthcoming years.

Virtual care pathways for people living with HIV: A mixed-methods systematic review.

BACKGROUND: The COVID-19 pandemic prompted an unprecedented surge in virtual services, necessitating a rapid shift to digital healthcare approaches. This review focuses on evaluating the evidence of virtual care (VC) in delivering HIV care, considering the complex nature of HIV and the need for tailored-approaches, especially for marginalized populations. METHODS: A mixed-methods systematic review was performed with searches on five databases, covering studies from January 1946 to May 2022. Inclusion criteria involved two-way virtual consultations between healthcare workers and people living with HIV (PLHIV), with detailed descriptions and outcomes. Qualitative and quantitative studies were included, and the risk of bias was assessed using the Newcastle-Ottawa score and Stenfors' framework. RESULTS: Among 4143 identified records, 26 studies met the criteria, with various models of care described. The majority of studies were observational, and videoconferencing was the primary mode of virtual consultation employed. Quantitative analysis revealed PLHIV generally accept VC, with high attendance rates (87%). Mean acceptability and satisfaction rates were 80% and 85%, respectively, while 87% achieved HIV viral suppression. The setting and models of VC implementation varied, with some introduced in response to COVID-19 while others were as part of trials. CONCLUSIONS: VC for PLHIV is deemed an acceptable and effective approach and is associated with good virological outcomes. Data on other health outcomes is lacking. The review underscores the importance of diverse models of care, patient choice and comprehensive training initiatives for both staff and patients. Establishing a 'gold standard' for VC models is crucial for ensuring appropriate and effective reviews of PLHIV in virtual settings.

Physiologically-based pharmacokinetic modelling of long-acting injectable cabotegravir and rilpivirine in pregnancy.

AIMS: Long-acting cabotegravir and rilpivirine have been approved to manage HIV in adults, but data regarding safe use in pregnancy are limited. Physiologically-based pharmacokinetic (PBPK) modelling was used to simulate the approved dosing regimens in pregnancy and explore if Ctrough was maintained above cabotegravir and rilpivirine target concentrations (664 and 50 ng/mL, respectively). METHODS: An adult PBPK model was validated using clinical data of cabotegravir and rilpivirine in nonpregnant adults. This was modified by incorporating pregnancy-induced metabolic and physiological changes. The pregnancy PBPK model was validated with data on oral rilpivirine and raltegravir (UGT1A1 probe substrate) in pregnancy. Twelve weeks' disposition of monthly and bimonthly dosing of long-acting cabotegravir and rilpivirine was simulated at different trimesters and foetal exposure was also estimated. RESULTS: Predicted Ctrough at week 12 for monthly long-acting cabotegravir was above 664 ng/mL throughout pregnancy, but below the target in 0.5% of the pregnant population in the third trimester with bimonthly long-acting cabotegravir. Predicted Ctrough at week 12 for monthly and bimonthly long-acting rilpivirine was below 50 ng/mL in at least 40% and over 90% of the pregnant population, respectively, throughout pregnancy. Predicted medians (range) of cord-to-maternal blood ratios were 1.71 (range, 1.55-1.79) for cabotegravir and 0.88 (0.78-0.93) for rilpivirine between weeks 38 and 40. CONCLUSIONS: Model predictions suggest that monthly long-acting cabotegravir could maintain antiviral efficacy throughout pregnancy, but that bimonthly administration may require careful clinical evaluation. Both monthly and bimonthly long-acting rilpivirine may not adequately maintain antiviral efficacy in pregnancy.

Anastrozole as a therapeutic option for gynecomastia in a person receiving antiretroviral therapy: Case report.

A middle-aged Caucasian man living with HIV, clinically stable (viral load <20 copies/mL) on injectable antiretroviral cabotegravir plus rilpivirine every 2 months presented with a 6-month history of bilateral enlargement of the breasts associated with pain. His hormonal profile was normal, and no other underlying cause was identified. He was diagnosed with idiopathic gynecomastia. Tamoxifen is an anti-oestrogen recommended for gynecomastia and has been described in people living with HIV but can potentially induce the activity of cytochrome P450 3A4 (CYP3A4), reducing rilpivirine concentrations, which consequently may cause virological failure and resistance. This is the same for other antiretroviral agents majorly induced by CYP3A4. To date, there have been no reported cases of using anastrozole as a treatment for gynecomastia in people living with HIV or of its co-administration with antiretroviral. We describe the use of an aromatase inhibitor instead of tamoxifen in a person living with HIV, diagnosed with gynecomastia.

Therapeutic drug monitoring and virological response at week 48 in a cohort of HIV-1-infected patients switching to dolutegravir/rilpivirine dual maintenance therapy (ANRS-MIE-BIRIDER study).

AIMS: Dolutegravir (DTG) and rilpivirine (RPV) dual therapy is now recommended as a switch option in virologically suppressed HIV patients. Literature suggests that virological failure with dual therapy could possibly relate to subtherapeutic drug concentrations. In this study, we aimed at describing the DTG and RPV trough plasma concentrations (Cmin) and plasma HIV-1 RNA viral load (VL) during maintenance dual therapy. METHODS: We performed a retrospective analysis of DTG and RPV therapeutic drug monitoring in people living with HIV/AIDS (PLWHA) with dual therapy in 9 French centres. DTG and RPV trough plasma concentrations were estimated using a Bayesian approach to predict Cmin. The relationship between the pharmacokinetics of DTG and RPV and VL > 50 copies (cp)/mL was explored using joint nonlinear mixed models. The frequency of subtherapeutic threshold (DTG Cmin below 640 ng/mL and RPV Cmin below 50 ng/mL) were compared between PLWHA presenting VL > 50 cp/mL or not during the study. RESULTS: At baseline, 209 PLWHA were enrolled in the study. At week 48, 19 people living with HIV/AIDS (9.1%) discontinued their treatment and 15 PLWHA (7.1%) exhibited VL > 50 cp/mL. Six PLWHA out of 15 (40.0%) with VL > 50 cp/mL during the follow-up had at least 1 Cmin below the respective thresholds while only 26/194 patients (13.4%) without virological replication had at least 1 concentration below the threshold (P = .015). CONCLUSION: A majority of PLWHA receiving DTG/RPV maintenance dual therapy demonstrated VL < 50 cp/mL but virological replication was more frequent in people living with HIV/AIDS with subtherapeutic Cmin.

Pharmacokinetics and tolerability of the maturation inhibitor GSK3640254 coadministered with darunavir/ritonavir and/or etravirine in healthy adults.

AIMS: This phase I study investigated potential drug-drug interactions of the maturation inhibitor GSK3640254 (GSK'254) with darunavir/ritonavir (DRV/RTV) and/or etravirine (ETR). METHODS: In this randomized, open-label, single-sequence, multiple-dose study, healthy participants received GSK'254 200 mg once daily alone or coadministered with DRV/RTV 600/100 mg twice daily (BID; n = 19), ETR 200 mg BID (n = 19) or DRV/RTV 600/100 mg + ETR 200 mg BID (n = 16) under fed conditions. Primary endpoints were steady-state area under the plasma concentration-time curve from time 0 to the end of the dosing interval (AUC0-τ ) and maximum observed concentration (Cmax ). Secondary endpoints included trough concentration (Cτ ), safety and tolerability. Pharmacokinetic parameters were calculated using standard noncompartmental analysis, and geometric least-squares mean ratios were derived from linear mixed-effects models. RESULTS: GSK'254 AUC0-τ (geometric least-squares mean ratio [90% confidence interval], 1.14 [1.00-1.29]), Cmax (1.07 [0.92-1.24]) and Cτ (1.17 [1.01-1.35]) were similar when administered alone and with DRV/RTV. Etravirine coadministration decreased GSK'254 AUC0-τ (0.53 [0.48-0.59]), Cmax (0.60 [0.53-0.68]) and Cτ (0.51 [0.39-0.66]). Similar reductions were not observed with GSK'254 + DRV/RTV + ETR (AUC0-τ , 0.94 [0.82-1.09]; Cmax , 0.89 [0.75-1.07]; Cτ , 1.02 [0.89-1.18]). GSK'254 had no meaningful effect on DRV/RTV or ETR concentrations. All reported adverse events (AEs) were grade 1; 3 led to withdrawal and resolved (rash, asymptomatic electrocardiogram T-wave inversion, periorbital oedema). Most common AEs were diarrhoea (n = 9) and headache (n = 7). No deaths or serious AEs occurred. CONCLUSION: GSK'254 pharmacokinetics was not meaningfully affected by DRV/RTV or DRV/RTV + ETR, but were reduced with only ETR; no new tolerability concerns were observed.

Drug-drug interactions between gender-affirming hormone therapy and antiretrovirals for treatment/prevention of HIV.

Transgender persons face a greater burden of HIV compared to cisgender counterparts. Concerns around drug-drug interactions (DDIs) have been cited as reasons for lower engagement in HIV care and lower pre-exposure prophylaxis (PrEP) uptake among transgender populations. It is therefore imperative for hormone therapy, PrEP and antiretroviral therapy providers to understand the DDI potential between these therapies. Studies of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) PrEP with feminizing hormone therapies (FHTs) show reduced plasma tenofovir concentrations, but intracellular concentrations of tenofovir-diphosphate are not reduced. Efficacy of PrEP is expected to be maintained despite this interaction. Masculinizing hormone therapies have no effect on tenofovir concentrations but may increase FTC to a nonclinically relevant extent. No interactions between FHT and cabotegravir or tenofovir alafenamide have been demonstrated. Administration of TDF/FTC PrEP has no effect on hormone levels in transmen or transwomen. PrEP is expected to be effective and safe in transpersons and should be provided to high-risk individuals regardless of gender affirming hormone use. Enzyme inducing/inhibiting antiretroviral therapy may decrease or increase, respectively, the concentrations of FHT and masculinizing hormone therapy. Unboosted integrase inhibitors or enzyme neutral non-nucleoside reverse transcriptase inhibitors are not expected to affect and are not affected by gender affirming hormones and can be considered in transmen and transwomen. Overlapping toxicities including weight gain, dyslipidaemia, cardiovascular disease and bone density effects should be considered, and antiretroviral modifications can be made to minimize toxicities. Interactions between supportive care medications should be assessed to avoid chelation interactions and hyperkalaemia.

Sub- and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study.

AIMS: Interindividual variations in efavirenz (EFV) plasma concentrations are extensive, but paediatric data on its consequences for viral control are scarce. The aim of this study was to explore the role of genetic variation in achieving therapeutic efavirenz plasma concentrations in a cohort of Ugandan children and the linkage between genetic CYP2B6 variants, EFV plasma variability, viral resistance and viral outcome. METHODS: Ninety-nine treatment-naïve children, aged 3-12 years and living with HIV, were followed for 24 weeks after ART initiation assessing mid-dose efavirenz plasma concentrations, HIV RNA, HIV drug resistance and adherence. Polymorphisms in genes coding for drug-metabolizing enzymes were genotyped. Efavirenz concentrations were determined by liquid chromatography coupled with high-resolution tandem mass spectrometry. Metabolizer phenotype was predicted from composite genotypes of CYP2B6 (c.516G>T and c.983 T>C). A mixed effects restricted maximum likelihood regression model was used to identify important factors for efavirenz exposure. RESULTS: Efavirenz plasma concentrations were below the therapeutic interval (1000-4000 mg/mL) in 12-17% and above in 21-24% of measurements. Eight children had persisting subtherapeutic concentrations, five of which failed virologically and three acquired at least one new resistant mutation. Multivariate modelling explained 70% of interindividual variation in plasma concentration, with treatment duration, adherence, CYP2B6c.136A>G, and metabolizer phenotype as independent predictors of EFV concentration. In univariate analysis, metabolizer phenotype explained 50% of interindividual variation. CONCLUSIONS: Metabolizer phenotype explained 50% of interindividual variation in efavirenz plasma concentration. Autoinduction was not confirmed and >33% of the concentrations were outside the therapeutic interval. Subtherapeutic concentrations worsened virological resistance and outcomes. Genotype-based dosing may help avert both sub- and supratherapeutic efavirenz plasma concentrations in Ugandan children.

Antiretroviral Treatment Gaps and Adherence Among People with HIV in the U.S. Medicare Program.

Approximately one-quarter of people with HIV (PWH) in the U.S. receive coverage through the Medicare program; however, no prior real-world study has examined antiretroviral therapy (ART) gaps and adherence and associated factors in this population. This retrospective cohort analysis used 2013-2018 national Medicare fee-for-service claims data to identify all PWH initiated on a new ART regimen including protease inhibitors [PI], non-nucleoside reverse transcriptase inhibitors [NNRTIs], or integrase strand transfer inhibitors [INSTIs] between 1/1/2014 and 12/31/2017. Study outcomes included ART adherence (based on proportion of days covered [PDC]), continuous treatment gaps ranging from 1 to 6 days to ≥ 180 days, and discontinuation (continuous gap ≥ 90 days) in the 12-month follow-up period. Multivariable regressions were used to assess factors associated with ART adherence and discontinuation. The final sample included 48,627 PWH (mean age: 54.5 years, 74.4% male, 47.5% White, 89.8% disabled). Approximately 53.0% of PWH had a PDC ≥ 0.95, 30.2% had a PDC between 0.70 and < 0.95, and 16.8% had PDC < 0.70. Treatment gaps of at least ≥ 7-days (55.2%) and ≥ 30-days (26.2%) were common and 10.1% PWH discontinued treatment. Younger age, female sex, Black race, higher comorbidity score, mental health conditions, and substance use disorder were associated with higher odds of lower adherence and discontinuation (all p-values < 0.05). In conclusion, suboptimal adherence and treatment gaps in ART use were commonly observed among PWH in Medicare. Interventions and policies to mitigate barriers to adherence are urgently needed in this population to both improve their survival and increase the potential for ending the HIV epidemic in the US.

Ensuring People Living with HIV Inform the Future of HIV Treatment in Low- and Middle-Income Countries: A Scoping Review and Recommendations for a Community-Led Research Agenda.

The HIV treatment landscape in low- and middle-income countries (LMICs) is rapidly evolving, exemplified by the expansion of differentiated service delivery (DSD) during the coronavirus disease (COVID-19) pandemic. Long-acting products represent a new frontier that will require a significant redesign of health systems. It is critical to understand service delivery and product preferences of people living with HIV (PLHIV) and ensure evidence generation is guided by community priorities. We conducted a scoping review to identify gaps among preference studies and inform future research. Peer-reviewed articles published from January 2014-May 2022 reporting acceptability or preference data from PLHIV or caregivers for one or more service delivery or product attribute were eligible. Service delivery studies were restricted to LMIC populations while product studies had no geographical restrictions. Based on gaps identified, we consulted advocates to develop community-led research agenda recommendations. Of 6,493 studies identified, 225 studies on service delivery attributes and 47 studies on product preferences were eligible. The most frequently studied delivery models were integration (n = 59) and technology-based interventions (n = 55). Among product literature, only 15 studies included LMIC populations. Consultation with advocates highlighted the need for research on long-acting products, including among pediatric, pregnant, and breastfeeding PLHIV, PLHIV on second-line regimens, and key populations. Consultation also emphasized the need to understand preferences on clinic visit frequency, side effects, and choice. While the preference literature has expanded, gaps remain around long-acting regimens and their delivery. To fill these gaps, the research agenda must be guided by the priorities of communities of PLHIV.

Depression is associated with poor self-reported adherence to antiretroviral therapy among people living with HIV attending an HIV clinic in the UK: results from a cross-sectional study.

Contemporary evidence is needed to assess whether the prevalence of depression remains high among people living with HIV in the United Kingdom despite recent efforts to improve patients' mental health, and if depression is negatively associated with individuals' adherence to antiretroviral therapy. In a secondary analysis of a cross-sectional clinic-based survey of alcohol consumption and associated health behaviour among people living with HIV in London, of the 221 respondents, 106 (48%) had poor self-reported adherence to antiretroviral therapy (CASE Index) and 69 (31%) screened positive for depression (PHQ-9). Poor self-reported adherence to ART was 72% higher among participants who screened positive for depression in comparison with participants who screened negative. Respondents who were younger, unemployed, and reported problematic drug use were more likely to screen positive for depression. Screening and management of depression as a part of routine HIV care may support adherence to antiretroviral therapy.

A Narrative Review of Novel Agents for Managing Heavily Treatment-Experienced People Living With HIV.

Objective: The objective of this review is to compare ibalizumab, fostemsavir, and lenacapavir, present the clinical trials evaluating each agent, and provide guidance on their use in highly-treatment experienced (HTE) population living with HIV (PWH). Data sources: A search of PubMed and clinicaltrials.gov was conducted using the search terms: ibalizumab, fostemsavir, and lenacapavir. Study selection and data extraction: English-language, clinical publications were included. Data synthesis: Ibalizumab, fostemsavir, and lenacapavir, are each first-in-class agents, that have major differences in mechanism of action, route and frequency of administration, pharmacokinetic parameters, including elimination half-life, potential for drug-drug interactions, safety profiles, and cost. Each has been shown, when combined with an optimized background regimen (OBR) with at least one other active agent, to achieve virologic suppression in HTE-PWH. Conclusion: In HTE-patients, adding ibalizumab, fostemsavir, and/or lenacapavir to at least one other active agent can lead to virologic suppression in this difficult to treat population. Monotherapy with any of these agents is not recommended and will lead to a high likelihood of drug resistance. Selection of which agent(s) to include with an OBR will depend on other patient factors including concomitant medications, acceptance of formulations (oral vs. subcutaneous vs. intravenous infusion), and potential access (both insurance-based and transportation). Adherence to all agents in the regimen is paramount to successful outcomes.

Cost-effectiveness of the prevention of parent-to-child transmission guidelines of HIV in India.

Background: One of the modes of transmission of HIV infection in India is from mother-to-child. In 2014, Prevention of Parent-to-child Transmission (PPTCT) guidelines of HIV in India were implemented which included shifting from Option A to Option B and B+. The aim of the present study was to evaluate health and cost related outcomes after implementation of these new guidelines. Methods: A decision analytical model was used to compare the PPTCT Option A with the new WHO Option of B and B+. Transmissions in serodiscordant couples and infants at 18 months were considered as health outcomes. The estimation of the cost for PPTCT services and HIV treatment was done using Costing Tool for Elimination Initiatives (CTEI) developed by National Center for Global Health and Medicine (NCGM). Results: The reduction in transmission rates in HIV infants was 33%. In serodiscordant couples the reduction in risk of HIV transmission from Option A to Option B and B+ was 72% and 87%, respectively. The incremental cost-effectiveness ratio (ICER) per quality adjusted life years (QALY) gained by averting infant infection, and for both infant and partner was US$ 238 and US$ 181 for Option B and US$ 1265 and US$ 947 for Option B+, respectively. Conclusion: It was found that Options B and B+ are more cost-effective as compared to option A. This effectiveness further increases when prevention of partner infections in Option B and B+ is taken into account.

Outcomes of Bariatric Surgery in People With Human Immunodeficiency Virus: A Retrospective Analysis From the ATHENA Cohort.

BACKGROUND: The implications of bariatric surgery (BS) on virologic and metabolic outcomes in people with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) are unknown. METHODS: Here, we report a retrospective analysis up to 18 months post-BS in PWH from the AIDS Therapy evaluation in The Netherlands (ATHENA) cohort with data from all dutch HIV treating Centers. Primary end points were a confirmed virologic failure (2 consecutive HIV-RNA measurements >200 copies/mL) and the percentage of patients who achieved >20% total body weight loss up to 18 months post-BS. Switches from baseline ART and trough plasma concentrations of antiretrovirals were also reported post-BS. Metabolic parameters and medication usage were compared pre- and post-BS. RESULTS: Fifty-one patients were included. One case of confirmed virologic failure and 3 cases with viral blips were detected in this cohort up to 18 months post-BS. Eighty-five percent of patients achieved >20% total body weight loss at 18 months post-BS, with a mean difference from baseline (95% confidence interval) of -33.5% (-37.7% to -29.3%). Trough plasma concentrations of measured antiretroviral agents were all above minimum effective concentrations, except for 1 sample of darunavir. Lipid profiles, but not serum creatinine and blood pressure, improved significantly (P < .01) post-BS. Total medications and obesity-related comedications declined from 203 to 103 and from 62 to 25, respectively, at 18 months post-BS. CONCLUSIONS: BS was an effective intervention for weight loss and lipid control in PWH using ART in this cohort with no clear link to poor virologic outcomes.

Medicaid Spending on Antiretrovirals From 2007 Through 2019.

BACKGROUND: Antiretroviral (ARV) medications to treat human immunodeficiency virus (HIV) are a major contributor to Medicaid prescription drug spending. Despite having been used for over 3 decades, the first generic ARVs only recently became available, and many newer versions continue to be sold at high prices despite within-class competition. We estimated Medicaid spending on ARVs from 2007 through 2019. METHODS: Using public Medicaid State Drug Utilization data, we identified trends in ARV spending and use from 2007 through 2019. We estimated net spending and average prices (spending per 30-day supply), accounting for statutory Medicaid rebates, including a 15%-23% base rebate plus additional rebates if a drug's price increased faster than inflation. RESULTS: Among 48 ARVs, estimated net Medicaid spending from 2007 through 2019 was $25 billion for 17 million 30-day supplies. Annual use increased 118%, from 0.7 million 30-day supplies in 2007 to 1.6 million in 2019. During this time, estimated annual net spending increased 178%, from $1.1 billion to $3.0 billion, and average net prices increased 28%, from $1432 to $1830 per 30-day supply. CONCLUSIONS: Annual Medicaid net spending on ARVs nearly tripled from 2007 to 2019, due to a combination of expanded use and rising prices. Medicaid did not extract expected benefits from its mandatory inflationary rebates because they were offset by use of newer, more expensive ARVs. To better control spending related to products with incremental innovation, the US government should be authorized to assure that launch prices for new drugs are aligned with the added benefit they offer over existing therapies.

Contribution of Low CD4 Cell Counts and High Human Immunodeficiency Virus (HIV) Viral Load to the Efficacy of Preferred First-Line Antiretroviral Regimens for Treating HIV Infection: A Systematic Review and Meta-Analysis.

We assessed whether low CD4 count and high viral load (VL) affect the response to currently preferred ART. We performed a systematic review of randomized, controlled clinical trials that analyzed preferred first-line ART and a subgroup analysis by CD4 count (≤ or >200 CD4/µL) or VL (≤ or >100 000 copies/mL). We computed the odds ratio (OR) of treatment failure (TF) for each subgroup and individual treatment arm. Patients with ≤200 CD4 cells or VL ≥100 000 copies/mL showed an increased likelihood of TF at 48 weeks: OR, 1.94; 95% confidence interval (CI): 1.45-2.61 and OR, 1.75; 95% CI: 1.30-2.35, respectively. A similar increase in the risk of TF was observed at 96 weeks. There was no significant heterogeneity regarding integrase strand transfer inhibitor or nucleoside reverse transcriptase inhibitor backbone. Our results show that CD4 <200 cells/µL and VL ≥100,000 copies/mL impair ART efficacy in all preferred regimens.