Switching Antiretroviral Therapy Research Articles

Treatment patterns and preferences of people living with HIV starting or switching antiretroviral therapy: Real-world evidence from Portugal.

There is a lack of up-to-date real-life evidence on antiretroviral therapy (ART) strategies among people living with HIV (PLWH) in Portugal. This study aimed to describe the treatment strategy used in PLWH either initiating or switching ART. Non-interventional, cross-sectional, multicenter study carried out between December 2019 and October 2021 in Portugal. A total of 237 PLWH were included in this study, 171 of whom were ART-experienced and 66 were ART-naïve. The study showed that triple regimens were the most common ART strategy and integrase strand transfer inhibitors-based therapy was the most frequently used therapeutic class in both ART-naïve and ART-experienced PLWH. Nevertheless, about a third of PLWH who started a triple regimen transitioned to a dual regimen. Patient-reported outcomes revealed high HIV literacy and similar ART preferences in both groups. This real-world study showed that triple regimens were the most widely used ART strategy, even after the European AIDS Clinical Society guidelines introduced the recommendation of a dual regimen for naïve patients. The cohorts of this study presented a high level of HIV literacy at the time of inclusion. Our findings highlighted that taking pills only once a day is considered a very important feature for most patients.

Cerebrospinal Fluid Viral Escape on Highly Active Antiretroviral Therapy: Analysis from Single Tertiary Care Centre.

HIV-infected individuals receiving regular antiretroviral therapy (ART) can present with a high viral load in cerebrospinal fluid (CSF) at times when it is suppressed in blood. This study presents data of HIV-infected patients who had undetectable or low plasma viral load in blood but presented with neurological signs and symptoms and were diagnosed to have CSF HIV viral escape. Records were reviewed for clinical manifestations, details of opportunistic or coinfection, and HIV viral copies in plasma and CSF at time of diagnosis of CSF escape. A total of 10,200 HIV-infected individuals were registered in HIV care till December 31, 2021. Nineteen individuals (14 virologically confirmed and 5 clinically) were diagnosed with high viral copies in CSF from June 2014 to December 2021. Mean age was 41.5 ± 9.2 (median, 39.5; range, 30-62) years. Average duration of antiretroviral treatment received at the time of diagnosis of CSF escape was 10.1 years. Median plasma HIV-viral copies were 2,469.8 (undetectable to 29,418) and in CSF were 12,773.7 (n = 14, range, 1,340-48,530) copies/mL. HIV viral copies in CSF were significantly higher than in plasma at the time of presentation (p = .003). ART regimen switch was done after identification of HIV CSF escape. Seventeen patients were alive with a regular follow-up of average 35 (range 7-66) months. All had documented clinical improvement with reversal of neurological impairment after ART switch. There was one death and one lost to follow-up. Early identification and timely intervention in CSF viral escape could revert severe neurological impairment and improves treatment outcome.

Navigating the Antiretroviral Therapy Switch Conundrum: Unveiling the Dilemma of Drug Resistance and Disease Progression in HIV/AIDS.

There is a need to establish consensus for harmonization in antiretroviral (ARV) therapy (ART) switch treatment strategy and address the dilemma that exists in terms of subpar immune response to therapy or an immunologic deterioration while on therapy. The purpose of thisreview is to identifythe factors that contribute to ARV treatment failure, such as insufficient dosage, drug interactions, poor adherence, drug resistance, and poor medication absorption. It is crucial to adopt a more efficient strategy to address this challenging dilemma. After ARV treatment failure, the aim of therapy is virologic suppression, which targets plasma viral load below the limits of detection as assessed by very sensitive tests with lower limits of quantification of 20 to 75 RNA copies/ml. The therapeutic objectives when complete virologic suppression is not possible, should be to maintain or restore immunologic function, stop the progression of the clinical illness, and minimize the emergence of new drug resistance that could further restrict the options for ARV drugs. Treatment history and drug-resistance testing, including the findings of previous and ongoing resistance tests, should be considered while selecting ARV regimens. Hence, the treatment approach post-ARV failure can be personalized based on clinical, immunologic, virologic, or as a mix of the three domains on a case-to-case basis. The evaluation of projected ARV activity should be based on treatment history and previous resistance test findings.

AGING WITH HIV: ASSOCIATION OF ART REGIMEN AND ADHERENCE TO VIRAL SUPPRESSION

Abstract Adherence to antiretroviral therapy (ART) is essential to effective management of HIV among an increasing population of older adults. Newer ART regimens are more “forgiving” of poor adherence allowing for viral suppression at lower adherence levels (i.e., < 90%). This is especially promising for some older adults who may struggle with adherence due to high rates of multimorbidity and polypharmacy. We aimed to determine how ART forgiveness varies depending on ART type and adherence. Data came from 2017-2019 claims and clinical records of 1,044 HIV-positive members of a Medicaid managed care plan who were 50 to 65 years of age. Pharmacy fill data were examined on a quarterly basis to characterize ART medications using latent class analysis (LCA), which captures the complexity of real-world ART usage (i.e., multiple medications, ART switching). LCA yielded five distinct ART utilization patterns over three years, mostly characterized by recent medications and formulations of ART, though they varied in number of tablets and in medication class (e.g., boosted protease inhibitors). Logistic regression models adjusting for demographics and health-related covariates revealed that ART medication patterns did not consistently differ in odds of maintaining viral suppression across adherence levels (< 50%, 50% to < 80%, 80% to < 85%, 85% to < 90%, and >=90%). In contrast, other factors, including nadir CD4 count and behavioral health conditions, were related to viral suppression across models. This highlights the importance of life-course illness trajectories when considering disease management and treatment strategies for older adults living with HIV, especially those with difficulty maintaining near-perfect adherence.

Pharmacogenetics of weight gain following switch from efavirenz- to integrase inhibitor-containing regimens.

Excessive weight gain affects some persons with HIV after switching to integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART). We studied associations between CYP2B6 genotype and weight gain after ART switch among ACTG A5001 and A5322 participants. Eligible participants switched from efavirenz- to INSTI-containing ART, had genotype data, and had weight data at least once from 4 weeks to 2 years post-switch. Multivariable linear mixed effects models adjusted for race/ethnicity, CD4, age, BMI and INSTI type assessed relationships between CYP2B6 genotype and estimated differences in weight change. A total of 159 eligible participants switched ART from 2007 to 2019, of whom 138 had plasma HIV-1 RNA < 200 copies/mL (65 CYP2B6 normal, 56 intermediate, 17 poor metabolizers). Among participants with switch HIV-1 RNA < 200 copies/mL, weight increased in all 3 CYP2B6 groups. The rate of weight gain was greater in CYP2B6 poor than in CYP2B6 normal metabolizers overall, and within 9 subgroups (male, female, White, Black, Hispanic, dolutegravir, elvitegravir, raltegravir, and TDF in the pre-switch regimen); only in Hispanic and elvitegravir subgroups were these associations statistically significant ( P < 0.05). Compared to normal metabolizers, CYP2B6 intermediate status was not consistently associated with weight gain. CYP2B6 poor metabolizer genotype was associated with greater weight gain after switch from efavirenz- to INSTI-containing ART, but results were inconsistent. Weight gain in this setting is likely complex and multifactorial.

Successful Multidrug-Resistant Tuberculosis Treatment Without HIV Viral Suppression: A Missed Opportunity.

Coinfection with multidrug-resistant tuberculosis (MDR-TB) and HIV is common, but few published studies examine how undergoing MDR-TB treatment affects HIV disease indicators. Using data from a nested, retrospective cohort of people with HIV (PWH) and successful MDR-TB treatment outcomes, we built multivariable regression models to explore correlates of HIV viral suppression at MDR-TB treatment completion. Among 531 PWH successfully treated for MDR-TB, mean age was 37.4 years (SD 10.2, interquartile range 30-43), 270 (50.8%) were male, 395 (74.4%) were virally suppressed at MDR-TB outcome, and 259 (48.8%) took bedaquiline. Older age (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI]: 1.01 to 1.06) increased odds of viral suppression, while having a prior TB episode (aOR 0.45, 95% CI: 0.31 to 0.64), having a detectable viral load at MDR-TB treatment initiation (aOR 0.17, 95% CI: 0.09 to 0.30), living in a township (aOR 0.49, 95% CI: 0.28 to 0.87), and being changed from efavirenz-based antiretroviral therapy (ART) to a protease inhibitor due to bedaquiline usage (aOR 0.19, 95% CI: 0.04 to 0.82) or not having an ART change while on bedaquiline (aOR 0.29, 95% CI: 0.11 to 0.75) lowered odds of viral suppression. Changing from efavirenz to nevirapine due to bedaquiline usage did not significantly affect odds of viral suppression (aOR 0.41, 95% CI: 0.16 to 1.04). Increased pill burden and adverse treatment effects did not significantly affect HIV viral suppression while switching ART to a protease inhibitor to accommodate bedaquiline or not changing ART while taking bedaquiline did, suggesting that PWH and MDR-TB may benefit from additional support if they must switch ART.

Hepatitis B infection or reactivation after switch to two-drug antiretroviral therapy: A case series, literature review, and management discussion.

Two-drug antiretroviral therapy (ART) without hepatitis B virus (HBV) activity is prescribed for persons with HIV as simplified or salvage therapy. While two-drug regimens are not recommended for persons with chronic HBV infection, guidelines do not address use in those with HBV susceptibility and/or core antibody reactivity. We present a case series of individuals with HBV infection or reactivation following switch to two-drug, non-HBV-active ART. HIV primary care clinics of an academic medical center in New York, NY. Case surveillance was conducted to identify persons with HBV surface antigenemia and viremia following two-drug ART switch. Clinical characteristics and outcomes were ascertained through chart review. Four individuals with HBV infection or reactivation after ART switch were identified. Two had HBV susceptibility, one had core antibody reactivity, and one had surface antigen reactivity pre-switch. All eligible persons had received HBV vaccination, two with low-level antibody response and one with persistent nonresponse. Two presented with fulminant hepatitis, one requiring liver transplantation. Two-drug ART switch may pose risk of HBV infection or reactivation. We propose careful patient selection and monitoring through the following: 1) Assessment of HBV serologies before switch and periodically thereafter, 2) Vaccination and confirmation of immunity before switch, 3) Risk stratification and counseling about HBV reactivation for those with core antibody, 4) Preemptive HBV DNA monitoring for those at risk of reactivation, 5) Continuation of HBV-active prophylaxis when above measures are not feasible, 6) Continuation of HBV-active therapy and surveillance for chronic HBV infection.

Knowledge and perceptions about Dolutegravir and Dolutegravir counselling: a qualitative study among women living with HIV

IntroductionIn 2018, the Malawi Ministry of Health adopted the recommendation to switch first-line antiretroviral therapy (ART) from an efavirenz (EFV)-based to a dolutegravir (DTG)-based regimen. Little is known about patients’ experience during this transition. We conducted a qualitative study to explore DTG-related counselling challenges among providers of HIV care and factors influencing regimen switching or non-switching among women living with HIV in Lilongwe, Malawi.MethodsBetween February-July 2020, we recruited participants who took part in DTG counselling on reasons to switch, side effects, and benefits from two government health facilities providing HIV care: Area 18 health centre and Bwaila district hospital in Lilongwe, Malawi. We purposively sampled and interviewed 8 women living with HIV who remained on an EFV-based regimen after counselling, 10 women who switched to a DTG-based regimen, and 10 HIV care providers who provided counselling about ART switching. In-depth interviews were used to explore patient’s perceptions of DTG, factors affecting the decision to switch, and both patient and provider experience with counselling. Interview data was coded for themes using inductive and deductive codes. Interviews were conducted until thematic saturation was achieved. Data matrices were used for analysis and thematic extraction.ResultsMost women in both groups were well versed on DTG’s potential side effects and felt well counselled on the benefits of switching, such as quicker viral load suppression. Many women associated DTG with birth defects and expressed concern. However, the primary reason for not switching was concern with how the new medication would be tolerated, especially when they were satisfied with their current regimen. Almost all providers expressed difficulty providing DTG counselling. Primary reasons included feeling inadequately trained and/or not having resources to use during counselling, such as diagrams or brochures.ConclusionDTG counselling was well accepted by women; however, some felt that their concerns were not fully addressed. Providers reflected this sentiment in that they did not feel adequately trained or well-equipped to provide adequate counselling. Training on counselling for new ART regimens should be intensified and utilize patient-centered educational materials to address the concerns raised by both patients and health care providers.

Laboratory Based Surveillance of HIV-1 Acquired Drug Resistance in Cameroon: Implications for Use of Tenofovir-Lamivudine-Dolutegravir (TLD) as Second- or Third-Line Regimens.

Increased HIV drug resistance (HIVDR) with antiretroviral therapy (ART) rollout may jeopardize therapeutic options, especially in this era of transition to fixed-dose tenofovir-lamivudine-dolutegravir (TLD). We studied acquired HIVDR (ADR) patterns and describe potentially active drugs after first- and second-line failure in resource-limited settings (RLS) like Cameroon. A laboratory-based study with 759 patients (≥15 years) experiencing virological failure was carried out at the Chantal Biya International Reference Centre (CIRCB), Yaoundé, Cameroon. Socio-demographic, therapeutic and immunovirological data from patient records were analysed according to HIV-1 genotypic profiles. Median (IQR) ART-duration was 63 (50-308) months. Median CD4 and viremia were 153 (IQR:50-308) cells/mm3 and 138,666 (IQR:28,979-533,066) copies/mL, respectively. Overall ADR was high (93.4% first-line; 92.9%-second-line). TDF, potentially active in 35.7% of participants after first-line and 45.1% after second-line, suggested sub-optimal TLD-efficacy in second-line (64.3%) and third-line (54.9%). All PI/r preserved high efficacy after first-line failure while only DRV/r preserved high-level efficacy (87.9%) after second-line failure. In this resource-limited setting (RLS), ADR is high in ART-failing patients. PI/r strategies remain potent backbones for second-line ART, while only DRV/r remains very potent despite second-line failure. Though TLD use would be preferable, blind use for second- and third-line regimens may be sub-optimal (functional monotherapy with dolutegravir) with high risk of further failure, thus suggesting strategies for selective ART switch to TLD in failing patients in RLS.

Reasons for antiretroviral switching in Colombia: A retrospective cohort study.

Long-term use of antiretroviral therapy (ART) for HIV infection might lead to the necessity of switching regimens. We aimed to analyze the reasons for the ART switch, the time-to-switch of ART, and its associated factors in a Colombian cohort. We conducted a retrospective cohort in 20 HIV clinics, including participants ≥18years old with confirmed HIV infection who underwent an ART switch from January 2017 to December 2019 with at least 6 months of follow-up. A time-to-event analysis and an exploratory Cox model were performed. 796 participants switched ART during the study period. The leading cause of ART switch was drug intolerance (n = 449; 56.4%) with a median time-to-switch of 12.2months. The longest median time-to-switch was due to regimen simplification (42.4months). People ≥50years old (HR = 0.6; 95% CI (0.5-0.7) and CDC stage 3 at diagnosis (HR = 0.8; 95% CI (0.6-0.9) had less hazard for switching ART over time. In this Colombian cohort, drug intolerance was the main cause of the ART switch, and the time-to-switch is shorter than reports from other countries. In Colombia, it is crucial to apply current recommendations for ART initiation to choose regimens with a better tolerability profile.

Treatment success of rescue regimens after dual therapy failure in people living with HIV in a real-life setting

Few data on the management of two-drug regimen (2DR) failure in people living with human immunodeficiency virus (PLWH) are available. Retrospective study on treatment-experienced PLWH on a 2DR, who underwent virological failure [(VF) two consecutive viral loads (VLs) ≥50 copies/mL, a single VL ≥1000 copies/mL, or an antiretroviral therapy (ART) switch after a single VL ≥50 copies/mL with previous blips] or discontinuation for toxicity (baseline). We included integrase strand transfer inhibitor (INSTI)-based [one INSTI plus one nucleoside reverse transcriptase inhibitor (NRTI) (n=78) or one non-NRTI (n=20)] or boosted protease inhibitor (PI/b)-based [one PI/b plus one NRTI (n=116) or one INSTI (n=12)] 2DRs. Probabilities of treatment success (TS), VF, and discontinuation for any other cause of rescue regimens were estimated by Kaplan-Meier curves. A stepwise Cox model was performed to assess predictors of TS. Overall, 226 PLWH were evaluated: at baseline, 144 individuals discontinued 2DR for toxicity and 82 had VF [median viremia 81 (63-212) copies/mL]; 171 switched therapy (49.7% to a triple-regimen, 40.9% to a different 2DR), while 55 (exclusively among those with VF) maintained their failing regimens. The probabilities of 12- and 24-month TS were 75.6% and 64.7%, respectively. Higher TS probabilities were observed in individuals who switched ART at 2DR failure (p=0.003) and in PLWH who discontinued 2DR for toxicity (p=0.008). A therapy switch was the only predictor of TS (p=0.002). Overall probability of success of rescue regimens introduced after 2DR failure is good; an immediate ART switch is associated with higher efficacy, so this approach should be encouraged.

Impact of weight gain with dolutegravir on antiretroviral adherence and viral suppression in four African countries.

We hypothesized that total body weight (TBW) gain after switching antiretroviral therapy (ART) regimen to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) may negatively impact ART adherence and viral load (VL) and therefore sought to examine these associations. The ongoing African Cohort Study (AFRICOS) enrols people with HIV at 12 facilities in Kenya, Nigeria, Tanzania and Uganda supported by The US President's Emergency Plan for AIDS Relief. Among ART-experienced participants who switched to TLD, we used multivariable multinomial logistic regression to examine associations between pre-/post-TLD changes in percentage TBW (≥5% gain, <5% change, ≥5% loss) and changes in self-reported ART adherence (0, 1-2, ≥3 days missed doses in past 30 days) and VL [(<50 copies/mL (undetectable), 50-999 copies/mL (detectable, but suppressed), ≥1000 copies/mL (unsuppressed)]. Among 1508 participants, median time from starting TLD to follow-up was 9 months (interquartile range: 7-11). Overall, 438 (29.1%) participants experienced a TBW gain ≥5%, which was more common among females than among males (32.2% vs 25.2%, p = 0.005) and participants switching from efavirenz [32.0% vs nevirapine (19.9%) and boosted protease inhibitor (20.0%); p < 0.001]. Compared with a TBW change <5% [950 (63.0%) participants], TBW gain ≥5% was not significantly associated with more days with missed ART doses [adjusted odds ratio (aOR) = 0.77, 95% confidence interval (CI): 0.48-1.23] or VL becoming detectable and/or unsuppressed (aOR = 0.69, 95% CI: 0.41-1.16). Although a substantial proportion of participants experienced weight gain after switching to TLD, we did not identify a significant impact on adherence or virological outcomes.

Antiretroviral therapy and weight gain in antiretroviral treatment-experienced HIV patients: A review.

The risk of developing non-AIDS events (NAEs) remains higher in persons living with HIV-1 (PLWH) compared to the general population despite progress made in the treatment by antiretroviral (ARV). Particular attention is therefore given to the management of risk factors associated with NAEs during the follow-up of PLWH, including overweight. Factors associated with weight gain in PLWH are multifactorial and include demographics, HIV disease-related, lifestyle, cultural, and antiretroviral therapy (ART)-associated factors. All these confounding factors make it difficult to interpret the potential link between ARVs and weight gain. In antiretroviral treatment- experienced PLWH, confounding factors such as the return to normal health or the advanced stage of disease can be ruled out compared to naïve patients which somewhat facilitates the interpretation of weight gain. Weight gain after ART switch is modest, not generally a big concern in clinical practice in this population and correlated more strongly with baseline regimen, especially after the stop of TDF or EFV, than with sex-, race-, or HIV-related factors. It remains uncertain whether this is due to the loss of a weight suppressive effect of prior regimens with older agent such as TDF or EFV or a weight gain effect of the newer regimens especially TAF and/or INSTI, or both. The mechanisms linked to weight gain attributed to the new ARVs as well as its possible reversibility are not yet elucidated. Clinicians who switched ARV regimen of experienced PLWH should be aware of this side effect and of this potentially consequences on the global health.

HIV virologic response, patterns of drug resistance mutations and correlates among adolescents and young adults: A cross-sectional study in Tanzania.

The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania. Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design. Dried blood spot (DBS) samples were collected and samples with a viral load (VL) ≥1000 copies/mL underwent genotyping for the HIV-1 pol gene. Stanford HIV database algorithm predicted acquired DRMs, Fisher's exact test and multivariable logistic regression assessed factors associated with DRMs and VS, respectively. We analyzed data of 578 AYA on antiretroviral therapy (ART) for 9-15 and ≥ 36 months; among them, 91.5% and 88.2% had VS (VL<1000copies/mL) at early and late time points, respectively. Genotyping of 64 participants (11.2%) who had VL ≥1000 copies/ml detected 71.9% of any DRM. Clinically relevant DRMs were K103N, M184V, M41L, T215Y/F, L210W/L, K70R, D67N, L89V/T, G118R, E138K, T66A, T97A and unexpectedly absent K65R. Participants on a protease inhibitor (PI) based regimen were twice as likely to not achieve VS compared to those on integrase strand transfer inhibitors (INSTI). The initial VL done 6 months after ART initiation of ≥1000copies/mL was the primary factor associated with detecting DRMs (p = .019). VS amongst AYA is lower than the third UNAIDs target. Additionally, a high prevalence of ADR and high levels of circulating clinically relevant DRMs may compromise the long-term VS in AYA. Furthermore, the first VL result of ≥1000copies/ml after ART initiation is a significant risk factor for developing DRMs. Thus, strict VL monitoring for early identification of treatment failure and genotypic testing during any ART switch is recommended to improve treatment outcomes for AYA.

1582. Real-World Use of Long-Acting Cabotegravir + Rilpivirine in the US: Effectiveness in the First Year

Abstract Background The first long-acting (LA) antiretroviral therapy (ART) regimen, cabotegravir+rilpivirine (CAB+RPV) injection, was approved by the FDA in January 2021 for ART-experienced, people with HIV (PWH) with undetectable viral load (VL&amp;lt; 50 copies/mL). We assessed clinical effectiveness of CAB+RPV LA in the first year of use in the United States (US). Methods Using electronic health record data from the OPERA® cohort, all ART-experienced adults who received ≥1 CAB+RPV LA prescriptions for the first time between 21Jan2021 and 28Feb2022 were followed until 13Mar2022. Discontinuation was defined as an ART switch or &amp;gt; 2 consecutive missed doses. VL were monitored from first injection until end of follow-up or discontinuation. Confirmed virologic failure was defined as 2 consecutive VLs &amp;gt; 200 copies/mL or 1 VL &amp;gt; 200 copies/mL + discontinuation. Results were stratified by VL at first prescription (i.e., suppressed: &amp;lt; 200 copies/mL; viremic: ≥ 200 copies/mL). Results Of 994 PWH prescribed CAB+RPV, all were ART-experienced and 85% had undetectable VL (&amp;lt; 50 copies/mL), 90% were suppressed (&amp;lt; 200 copies/mL), and the remainder had VL ≥200/mL (6%) or missing baseline VL (4%). Of those prescribed, 344 (38%) received CAB+RPV LA injections over a median 53 (IQR: 35, 79) days; 14% were women, 36% were Black, 29% were Hispanic, 25% had a BMI of ≥30, and the median age was 40 (IQR: 32, 53) years (Table 1). At the end of observation, 62% had not yet received CAB+RPV injections as they were in the process of approval, were on oral lead-in, or had been denied. At study end, 310 (90%) of the 344 remained on CAB+RPV LA with median follow-up of 3.4 (2.2, 6.1) months. Among those with VLs after first injection, the last VL was &amp;lt; 200 copies/mL in 99% and &amp;lt; 50 copies/mL in 94% (Table 2); all follow-up VLs were &amp;lt; 200 copies/mL in 97%, and &amp;lt; 50 copies/mL in 88%. Thirty viremic PWH received CAB+RPV LA injections (Table) with a median VL at first prescription of 4.2 (IQR: 3.2, 4.9) log copies/mL. Five or fewer PWH experienced confirmed virologic failure in each of the suppressed and viremic groups. Conclusion In this real-world cohort of PWH who received CAB+RPV LA injections in the US, observations from the first year suggest that this regimen is effective among virologically suppressed individuals. Disclosures Michael G. Sension, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Honoraria Ricky K. Hsu, MD, Gilead: Honoraria|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck &amp; Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck &amp; Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employment Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds Andrew Zolopa, MD, ViiV Healthcare: full time employee|ViiV Healthcare: Stocks/Bonds Jean A. van Wyk, MB,ChB; MFPM, ViiV Healthcare Limited: I am an employee of ViiV Healthcare|ViiV Healthcare Limited: Stocks/Bonds Gregory P. Fusco, MD, MPH, AIDS Healthcare Foundation: Client of employer|EMD: Grant/Research Support|Gilead Sciences: Client of employer|Janssen: Client of employer|Merck &amp; Co.: Client of employer|Theratechnologies: Client of employer|ViiV Healthcare: Client of employer.

1256. Antiretroviral Switching in Colombia: A Retrospective Cohort Study.

Abstract Background Antiretroviral therapy (ART) for the human immunodeficiency virus (HIV) has improved life expectancy in people living with HIV/AIDS (PLWHA). Between 2.4% and 50% of PLWHA who initiate ART require a regimen switch within the first year. This variable range depends on local treatment guidelines, available ART, and the prevalence of resistance. We aimed to analyze the causes of ART Switch, time to ART switch and its associated factors in a Colombian Cohort. 1. a. Kaplan Meier Curves and Log-Rank test for time to antiretroviral therapy switch by sex in a cohort of people living with HIV in Colombia 2017-2019. Log-rank test, p: 0.0091. b. Kaplan Meier Curves and Log-Rank test for time to antiretroviral therapy switch by age in a cohort of people living with HIV in Colombia 2017-2019. Log rank test, p: &amp;lt;0.0001. c. Kaplan Meier Curves and Log-Rank test for time to antiretroviral therapy switch by CDC Stage in a cohort of people living with HIV in Colombia 2017-2019. Log rank test, p: 0.006. d. Kaplan Meier Curves and Log-Rank test for time to antiretroviral therapy switch by CD4 cell count in a cohort of people living with HIV in Colombia 2017-2019. Log rank test, p: 0.096 Methods We conducted a retrospective cohort study in 20 different HIV clinics including patients ≥18 years with confirmed HIV who underwent ART switching from 2017 to 2019 and with at least 6 months of follow up in their HIV Clinic. A time to event analysis and an exploratory Cox model were performed. Also, we conducted a logistic regression for comparing people with only one switch versus those who had 2 or more switches. Results 796 patients switched ART during the study period. Most of the patients were man (77.1%) and younger than 50 years (71.6%). The main cause of ART switch was tolerability (56.4%) followed by virologic failure (17.2%). Tolerability had a median time to switch of 12.2 months being the shortest, whereas the longest median time to switch was due to simplification (42.4 months). The Kaplan Meier curve and log-rank test for time to antiretroviral therapy switch by age, sex, CD4 count, and CDC stage are shown in Figure 1. In the Cox model we found that people with 50 years or older (HR= 0.6; 95% CI (0.5-0.7) and CDC stage 3 (HR= 0.8; 95% CI (0.6-0.9) had less hazard for switching ART over time. When comparing patients with only one ART switch versus those who had two or more ART switches, we found that having dyslipidemia increased the odds of switching ART more than one time (aOR=1.6; 95%CI (1.1-2.4). As opposed to having CD4 counts greater than 200 cell/mL which decreases the odds of having more than one ART switch. (aOR= 0.5; 95%CI (0.2-0.9) Table 1. Conclusion In this Colombian cohort, tolerability was the main cause of ART switch and the time to change the first ART is shorter than reports in other countries. Dyslipidemia and having CD4 counts smaller than 200 cells/mL increased the odds for requiring two or more changes. In Colombia is crucial to apply current recommendations of ART initiation in order to choose regimens with a better tolerability profile. Disclosures Sandra Valderrama, Infectologa, MSD: Advisor/Consultant.

Epidemiology, comorbidities at diagnosis and outcomes associated with HIV late diagnosis from 2010 to 2019 in a Belgian reference centre: A retrospective study.

Our objective was to investigate the demographic factors, comorbidities, and outcomes of patients with a late diagnosis (LD) of HIV in a Belgian HIV reference centre. All patients with HIV who presented for care between 2010 and 2019 were included. They were excluded if time between diagnosis and presentation or first CD4 count exceeded 6months or if they had previously received antiretroviral therapy (ART). LD was defined as a CD4 cell count ≤350/mm3 or an AIDS-defining event at diagnosis. Data were retrospectively collected and included data on demographic variables, cardiovascular risk factors, comorbidities at diagnosis, first prescribed ART, and outcomes. Logistic regression was used to determine factors associated with LD. Of 1078 patients, 427 (39.6%) were LD. In multivariable analysis, the following factors were associated with LD: non-homosexual transmission route, being born in Sub-Saharan Africa (SSA), and age ≥35 years. Prevalence at diagnosis of malignancies, diabetes, and cardiovascular diseases did not differ between non-LD and LD, whereas renal impairment was more frequent in LD. In univariable analysis, high-density lipoprotein (HDL) cholesterol <40 mg/dL and estimated glomerular filtration rate <60 ml/min were associated with LD; in multivariable analysis, only HDL cholesterol <40 mg/dL was associated. Patients with LD experienced more adverse events leading to a switch in ART, virological failure, and death during follow-up. LD remains common in our centre, especially in non-homosexual patients and those born in SSA. Although not associated with an important burden of comorbidities at diagnosis, it still results in poorer outcomes, emphasizing the need to expand coverage and access to HIV testing.

Changes in Quality of Sleep, Mood, and Other Neuropsychiatric Symptoms After Switching Dolutegravir/Lamivudine/Abacavir to Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Randomized Study of People With Human Immunodeficiency Virus With Poor Sleep Quality: GESIDA 10418.

BackgroundAlthough switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality.MethodsThis is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives.ResultsWe included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS.ConclusionsIn patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.

Retrospective Review of ART Regimens in HIV-Positive to HIV-Positive Kidney Transplant Recipients

IntroductionThe management of complex interactions between antiretroviral therapy (ART) and calcineurin inhibitor (CNI) immunosuppression regimens in HIV-positive to HIV-positive renal transplant recipients can be challenging. Literature describing ART regimens and indications for regimen switching in these patients is limited.MethodsThis retrospective review included 53 HIV-positive to HIV-positive renal transplant recipients. Data on ART regimens, reasons for ART switching, and timing of switches were described from day of transplant to study endpoint (end of study date, death, or graft failure). The association between rejection and ART regimen (protease inhibitor [PI] -based vs. non-PI-based regimen) was analyzed using negative binomial regression.ResultsThere were a total of 46 switches in 31 of 53 patients (58%). Protocol switches (n = 17 of 46, 37%) accounted for most switches, of which the majority were from non-nucleoside reverse transcriptase inhibitors (NNRTIs) to PIs. Other common reasons for switching include cytochrome P450 enzyme induction from efavirenz (EFV) (9 of 46, 20%), tenofovir disoproxil fumarate (TDF) nephrotoxicity (8 of 46, 17%) or side effects (6 of 46, 13%). Of the 46 switches, nearly half (n = 21, 46%) occurred during the transplant admission period, and approximately two-thirds (n = 28, 62%) were during the first year post-transplantation. There was an association between rejection and being maintained on a PI-based regimen (incidence rate ratio 2.77 (95% confidence interval 1.03–7.48), P = 0.044).ConclusionDespite frequent switching of ART regimens, HIV viral loads remained supressed and graft function remained stable in most HIV-positive kidney transplant recipients in our cohort. There was however a concerning signal for increased rejection rates in those on a PI-based regimen.

Real-world use and outcomes of dolutegravir-containing antiretroviral therapy in HIV and tuberculosis co-infection: a site survey and cohort study in sub-Saharan Africa.

IntroductionDolutegravir is being scaled up globally as part of antiretroviral therapy (ART), but for people with HIV and tuberculosis co‐infection, its use is complicated by a drug–drug interaction with rifampicin requiring an additional daily dose of dolutegravir. This represents a disadvantage over efavirenz, which does not have a major drug–drug interaction with rifampicin. We sought to describe HIV clinic practices for prescribing concomitant dolutegravir and rifampicin, and characterize virologic outcomes among patients with tuberculosis co‐infection receiving dolutegravir or efavirenz.MethodsWithin the four sub‐Saharan Africa regions of the International epidemiology Databases to Evaluate AIDS consortium, we conducted a site survey (2021) and a cohort study (2015–2021). The cohort study used routine clinical data and included patients newly initiating or already receiving dolutegravir or efavirenz at the time of tuberculosis diagnosis. Patients were followed from tuberculosis diagnosis until viral suppression (<1000 copies/ml), a competing event (switching ART regimen; loss to program/death) or administrative censoring at 12 months.ResultsIn the survey, 86 of 90 (96%) HIV clinics in 18 countries reported prescribing dolutegravir to patients who were receiving rifampicin as part of tuberculosis treatment, with 77 (90%) reporting that they use twice‐daily dosing of dolutegravir, of which 74 (96%) reported having 50 mg tablets available to accommodate twice‐daily dosing. The cohort study included 3563 patients in 11 countries, with 67% newly or recently initiating ART. Among patients receiving dolutegravir (n = 465), the cumulative incidence of viral suppression was 58.9% (95% confidence interval [CI]: 54.3–63.3%), switching ART regimen was 4.1% (95% CI: 2.6–6.2%) and loss to program/death was 23.4% (95% CI: 19.7–27.4%). Patients receiving dolutegravir had improved viral suppression compared with patients receiving efavirenz who had a tuberculosis diagnosis before site dolutegravir availability (adjusted subdistribution hazard ratio [aSHR]: 1.47, 95% CI: 1.28–1.68) and after site dolutegravir availability (aSHR 1.28, 95% CI: 1.08–1.51).ConclusionsAt a programmatic level, dolutegravir was being widely prescribed in sub‐Saharan Africa for people with HIV and tuberculosis co‐infection with a dose adjustment for the drug–drug interaction with rifampicin. Despite this more complex regimen, our cohort study revealed that dolutegravir did not negatively impact viral suppression.