atazanavir/ritonavir / Generic mfg. - LARVOL DELTA

Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum (clinicaltrials.gov) - P=N/A | N=205 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting | N=325 ➔ 205

Enrollment change • Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Weight Change in Trial of Switching From Second-Line bPI to B/F/TAF in a Context of Food Insecurity (CROI 2025) - "At enrollment, 175 (60%) were taking lopinavir/r and 115 (40%) atazanavir/r; 226 (78%) were taking tenofovir disoproxil fumarate, 51 (18%) zidovudine, and 13 (4%) abacavir; all were taking lamivudine or emtricitabine. In contrast, we observed weight loss in the standard of care group, which may have different clinical implications in settings with high rates of food insecurity. Understanding the implications of weight gain after stopping TDF is essential to guide global policies on TDF-sparing regimens."

Clinical

Plasma Concentrations of Lenacapavir in People Living With Multidrug-Resistant HIV: Real-Life Study (CROI 2025) - "Of note, 5 patients presented LEN Cpl above 150 ng/mL, corresponding to PWH with acute or chronic kidney disease and/or receiving ritonavir-boosted atazanavir containing regimens. Conclusions In our population of HTE HIV patients, PWH had adequate LEN Cpl. No drug-drug interaction was reported and tolerance of antiretroviral multitherapy was acceptable."

Clinical • Chronic Kidney Disease • Human Immunodeficiency Virus • Infectious Disease • Nephrology • Renal Disease

Kidney disease among adults on tenofovir-based second-line antiretroviral therapy in Dar es Salaam, Tanzania. (PubMed, South Afr J HIV Med) - "Tenofovir disoproxil fumarate (TDF) can result in proximal tubulopathy and acute tubular injury, whereas atazanavir/ritonavir (ATV/r) can cause interstitial nephritis and renal stones, both of which can lead to chronic kidney disease...Low eGFR (< 90 mL/min per 1.73 m2) was found in 22% of patients, proportionately higher among patients on ATV/r compared to those on a lopinavir/ritonavir (LPV/r) (P < 0.05)...Adults on second-line ART containing TDF were found to have a high prevalence of renal kidney disease in the Tanzanian context. Predictors of kidney disease were older age, proteinuria, and ATV/r-based regimen as compared to LPV/r."

Journal • Chronic Kidney Disease • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease

Intracellular Penetration of Atazanavir, Ritonavir and Dolutegravir With Concomitant Rifampicin: A Dose Escalation Study. (PubMed, Clin Pharmacol Ther) - "Ritonavir-boosted atazanavir is a victim of drug-drug interaction with rifampicin, a key component of antitubercular treatment. Finally, further, increasing the rifampicin dose did not show an additional impact on atazanavir/ritonavir concentrations in PBMC. The study confirms that increasing the ATV/r dose can be an effective strategy for compensating rifampicin effects even at the intracellular level, supporting its use in clinical settings."

Journal • Human Immunodeficiency Virus • Infectious Disease

Atherogenic Index of Plasma and High-Sensitivity C-Reactive Protein Levels Among People Living With HIV on Dolutegravir and Ritonavir-Boosted Atazanavir-Based Antiretroviral Therapy and Their Correlations to CD4 Cell Counts. (PubMed, AIDS Res Treat) - " From the study conducted, it can be concluded that the higher levels of AIP and hsCRP were seen in patients treated by ATV/r than in DTG-based regimens of ART and in PLWH with low CD4 cell counts. Therefore, routine monitoring of both AIP and hsCRP levels was a good marker of HIV disease progression and cardiovascular disease risk assessment in PLWH, particularly in developing countries where CD4 cell count testing is expensive and not easily available."

Journal • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • CD4 • CRP

Antiretroviral therapy in pregnancy in England in 2019‐2022: common regimens and treatment modifications (HIV-Glasgow 2024) - "Among pregnancies conceived on ART, most common (reported in >5%) first regimens were efavirenz (EFV) + tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) (13.5% [267/1974]), rilpivirine (RPV) +TDF+FTC (11.6% [228/1974]), darunavir/ritonavir (DRV/r) +TDF+FTC (8.0% [158/1974]), dolutegravir (DTG) + lamivudine (3TC) + abacavir (ABC) (7.7% [152/1974]), and raltegravir (RAL) +TDF+FTC (6.4% [127/1974]). Where ART was initiated during pregnancy (55.7% [234/420] diagnosed antenatally), median gestational age at start was 15 weeks (IQR 12–19); most common first regimens were RAL+TDF+FTC (17.7% [75/423]), DRV/r+TDF+FTC (15.4% [65/423]), atazanavir/ritonavir (ATV/r) +TDF+FTC (12.5% [53/423]), DTG+3TC+ABC (9.2% [39/423]) and DTG+TDF+FTC (8.3% [35/423])...3TC, lamivudine; ABC, abacavir; ATV/c, atazanavir/cobicistat; ATV/r, atazanavir/ritonavir; BIC, bictegravir; DRV/c, darunavir/cobicistat; DRV/r, darunavir/ritonavir; DTG, dolutegravir; EFV, efavirenz; EVG/c,..."

Human Immunodeficiency Virus • Infectious Disease

Outcomes following prenatal exposure to DTG‐containing antiretroviral therapy regimens: data from the DOLOMITE‐EPPICC study (HIV-Glasgow 2024) - "Our analysis focussed on five DTG-containing regimens: DTG+lamivudine (3TC) +abacavir (ABC), DTG+tenofovir disoproxil fumarate (TDF) +emtricitabine (FTC), DTG+tenofovir alafenamide (TAF) +FTC, DTG+3TC and DTG+rilpivirine (RPV)...The earliest DTG-containing regimen was DTG+3TC+ABC in 468 (56.2%), DTG+TDF+FTC in 132 (15.9%), DTG+TAF+FTC in 23 (2.8%), DTG+3TC/RPV in seven (0.8%) pregnancies. Of the remaining 203 (24.4%) pregnancies with other first DTG-containing regimens, most (78.8% [160/203]) were on regimens containing a drug from an additional anchor class (e.g. darunavir/ritonavir+TDF+FTC+DTG, atazanavir/ritonavir+TDF+FTC+DTG)...aDTG+3TC (n = 3) or DTG+RPV (n = 4)... The birth defect prevalence reported here is consistent with rates reported for DTG-exposed pregnancies in the Antiretroviral Pregnancy Registry (3.96%). Monitoring of use and safety of DTG-containing regimens in pregnancy is ongoing in EPPICC, as sample size for some groups is too small to exclude..."

Human Immunodeficiency Virus • Infectious Disease • Small for Gestational Age

Physiologically based pharmacokinetic modeling of drug-drug interactions between ritonavir-boosted atazanavir and rifampicin in pregnancy. (PubMed, CPT Pharmacometrics Syst Pharmacol) - P=N/A | "Thus, PBPK modeling suggests ATV/r 300/100 mg BD could maintain antiviral efficacy when co-administered with rifampicin 600 mg OD in pregnancy. Clinical studies are warranted to confirm safety and efficacy in pregnancy."

Journal • PK/PD data • CYP3A4

Antiretroviral Therapy with Ritonavir-Boosted Atazanavir- and Lopinavir-Containing Regimens Correlates with Diminished HIV-1 Neutralization. (PubMed, Vaccines (Basel)) - "These findings suggest that exposure to immature virions via b-PI use reduces neutralizing antibody responses, highlighting the importance of virion maturation in antibody induction. ART regimens promoting exposure to mature virions may enhance neutralization, with potential implications for HIV vaccine design. Further research is needed to explore implications for HIV vaccine design, especially using virus-like particles."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Evaluation of Viral Suppression in Paediatric Populations: Implications for the Transition to Dolutegravir-Based Regimens in Cameroon: The CIPHER-ADOLA Study. (PubMed, Biomedicines) - "VS was 85.1% on a DTG-based regimen versus 80.0% on efavirenz/nevirapine and 65.6% on lopinavir/ritonavir or atazanavir/ritonavir. Predictors of non-VS are younger age, non-TDF/3TC- and non-DTG-based regimens. Thus, efforts toward eliminating paediatric AIDS should prioritise the transition to a DTG-based regimen in this new ART era."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Deep learning assessment of senescence-associated nuclear morphologies in mammary tissue from healthy female donors to predict future risk of breast cancer: a retrospective cohort study. (PubMed, Lancet Digit Health) - "Assessment of senescence-associated nuclear morphologies with deep learning allows prediction of future cancer risk from normal breast biopsy samples. The combination of multiple models improved prediction of future breast cancer compared with the current clinical benchmark, the Gail model. Our results suggest an important role for microscope image-based deep learning models in predicting future cancer development. Such models could be incorporated into current breast cancer risk assessment and screening protocols."

Journal • Retrospective data • Breast Cancer • Oncology • Solid Tumor

Serum uric acid and high-sensitivity C-reactive protein levels among people living with HIV on dolutegravir and ritonavir-boosted atazanavir-based antiretroviral therapy: a comparative cross-sectional study. (PubMed, Front Med (Lausanne)) - "It is observed that DTG-based and ATV/r-based ART are associated with hyperuricemia and increased high-sensitivity C-reactive protein levels, respectively. Therefore, it is important to consider and evaluate serum uric acid and high-sensitivity C-reactive protein levels in patients taking DTG and ATV/r-based ART, as well as among those on HAART for years and with a higher waist circumference, so as to detect and prevent early the risk of having CVD."

Journal • Observational data • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • CRP

Increasing levels of protease inhibitor resistance in the South African public sector: implications for salvage treatment in the dolutegravir era (AIDS 2024) - "BACKGROUND: Following WHO recommendation in 2022, many countries implemented tenofovir-lamivudine-dolutegravir (TLD) as the regimen of choice...The overall prevalence of darunavir resistance was higher in ritonavir-boosted lopinavir (LPV/r)-exposed PLWH (13.5%) compared to ritonavir-boosted atazanavir (ATZ/r) exposed PLWH (9.3%, p<0.0001). We observed a notable increase in PI resistance, including resistance to darunavir, in South Africa since 2015. Despite the availability of TLD, performing HIVDR testing, in PLWH failing PI-based regimens, prior to switching to TLD, is recommended to assess the value of darunavir in salvage regimens."

Human Immunodeficiency Virus • Infectious Disease

Switching from a second-line ritonavir-boosted protease inhibitor (PI/r)-based regimen to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF): results of a randomized clinical trial (AIDS 2024) - "At enrollment, 180 (59.8%) were taking lopinavir/r and 121 (40.2%) atazanavir/r; 234 (77.7%) were taking TDF, 54 (17.9%) zidovudine, and 13 (4.34%) abacavir; all were taking lamivudine or emtricitabine. Switching virally suppressed adults on a second-line PI/r regimen to B/F/TAF is non-inferior to continuing PI/r-based ART. Rates of viral suppression were high in both groups."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease

Dolutegravir with recycled nucleoside reverse transcriptase inhibitors maintains better viral suppression than protease inhibitor based antiretroviral therapy over 144 weeks: VISEND Trial (AIDS 2024) - "We randomized adults with viral load (VL) < 1000 copies/mL on tenofovir disoproxil fumarate (TDF), lamivudine (3TC) plus efavirenz (EFV) or nevirapine (NVP) to TDF,3TC,DTG (TLD) or tenofovir alafenamide fumarate (TAF), emtricitabine (FTC), DTG (TAFED) [Arm A]. Participants with VL < 1000 copies/mL were randomized to TLD or TAFED or standard-of-care (SOC) second line comprising Lopinavir/ritonavir (LPV/r) or atazanavir/r (ATV/r), zidovudine (ZDV), 3TC [Arm B]...In those randomised to TDF/3TC/DTG and TAF/FTC/DTG, 61% and 52% had no predicted tenofovir activity respectively; whereas 75% had no predicted lamivudine or emtricitabine activity in both groups... In the VISEND trial, HIV-positive adults with virologic failure to TDF/3TC/NNRTI, had favourable outcomes when switched to DTG with recycled NRTIs compared to those switched to SOC boosted-PI despite high baseline resistance to NRTIs. No emergent INSTI mutations were reported at week 144. We recommend recycling of..."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

Early learnings from Zambia's introduction of darunavir/ritonavir (DRV/r) for second-line HIV treatment (AIDS 2024) - "With national scale-up underway, the programme reflects on early learnings to inform further scale-up within Zambia and the broader region.DESCRIPTION: The first phase of Zambia's 2L DRV/r introduction began in 2022 in 15 sites across 3 provinces, prioritizing recipients of care (ROC) failing dolutegravir-based first-line (1L) regimens. Phase II, starting in early 2023, expanded eligibility to ROC on atazanavir/ritonavir and increased the geographic footprint to 35 sites...Critical components of the successful introduction process included partnerships with communities, through engagement meetings and joint supportive supervision visits and monthly virtual mentoring sessions.LESSONS LEARNED: Data collected during supervision visits and interviews with healthcare workers (HCW) and ROC yielded the following lessons: (1) Quality and ongoing training and mentorship is critical to empower HCW to feel confident making switching decisions for 2L ROC, especially amidst HCW..."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases • Tuberculosis

In utero exposure to atazanavir-based antiretroviral regimens in a mouse model shows differential long-term motor and cognitive deficits dependent on the NRTI-backbone (AIDS 2024) - "Here we present our findings of neurocognitive outcomes in adult mice exposed in utero to ART. Dams were treated with a combination of ritonavir-boosted atazanavir with either abacavir plus lamivudine (ABC/3TC+ATV/r) or tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC+ATV/r), or water as a control, administered daily from day of plug detection to birth. In our murine model, in utero ART exposure had long-term effects on brain development and cognitive and motor outcomes in adulthood. Our data show that neurological outcomes can be influenced by the type of nucleoside reverse transcriptase inhibitor backbone of the regimen and not just the base drug, and display sex differences."

Preclinical • Cognitive Disorders • Human Immunodeficiency Virus • Infectious Disease • BDNF

Population Pharmacokinetic Analysis of Dolutegravir in Treatment-Experienced Adults Living with HIV-1. (PubMed, J Clin Pharmacol) - "The World Health Organization has recommended the use of dolutegravir (DTG) for both first and second-line antiretroviral treatment in both adults and children down to 4 weeks of age. Weight, smoking status, use of metabolic inducers as part of background antiretroviral therapy (ART) classified by their level of induction, use of atazanavir or atazanavir-ritonavir as part of background ART, and albumin level were predictors of CL/F; weight and albumin level were predictors of V/F; and sex and concomitant use of metal cation-containing vitamin/mineral supplements were predictors of relative bioavailability (F). The current model-based analysis suggests that the DTG dose adjustment is not required based on the demographics, laboratory values, smoking status, concomitant use of mild metabolic inducers or inhibitors in the background therapy, or use of metal cation-containing vitamin/mineral supplements because these covariate effects are not predicted to have a clinically..."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Perinatal exposure to atazanavir-based antiretroviral regimens in a mouse model leads to differential long-term motor and cognitive deficits dependent on the NRTI backbone. (PubMed, Front Mol Neurosci) - "Dams were treated with a combination of ritonavir-boosted atazanavir with either abacavir plus lamivudine (ABC/3TC + ATV/r) or tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC + ATV/r), or water as a control, administered daily from day of plug detection to birth. In our model, in utero ART exposure had long-term effects on brain development and cognitive and motor outcomes in adulthood. Our data show that neurological outcomes can be influenced by the type of nucleoside reverse transcriptase inhibitor backbone of the regimen and not just the base drug, and display sex differences."

Journal • Preclinical • Cognitive Disorders • Human Immunodeficiency Virus • Infectious Disease • BDNF

Switching From a Second-Line Boosted PI Regimen to B/F/TAF: Results of a Randomized Clinical Trial (CROI 2024) - "At enrollment, 175 (60%) were taking lopinavir/r and 115 (40%) atazanavir/r; 226 (78%) were taking tenofovir disoproxil fumarate, 51 (18%) zidovudine, and 13 (4%) abacavir; all were taking lamivudine or emtricitabine. Switching virally suppressed adults on a second-line PI/r regimen to B/F/TAF is non-inferior to continuing PI/r-based ART. Rates of viral suppression were high in both groups."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease

Serum Lipid Profiles, Blood Glucose, and High-Sensitivity C-Reactive Protein Levels Among People Living with HIV Taking Dolutegravir and Ritonavir-Boosted Atazanavir-Based Antiretroviral Therapy at Jimma University Medical Center, Southwest Ethiopia, 2021. (PubMed, HIV AIDS (Auckl)) - "When compared to ritonavir-boosted atazanavir-based regimens, dolutegravir had favorable lipid profiles and high-sensitivity C-reactive protein but unfavorable blood glucose levels. Therefore, baseline blood glucose, lipid profiles, and high-sensitivity C-reactive protein levels should be routinely measured in patients on these regimens."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • CD4 • CRP

Body weight and blood pressure changes on dolutegravir-, efavirenz- or atazanavir-based antiretroviral therapy in Zimbabwe: a longitudinal study. (PubMed, J Int AIDS Soc) - "Among PLHIV starting ART or switching to a new regimen, DTG-based ART was associated with larger weight gains and a substantial increase in the prevalence of high blood pressure. Routine weight and blood pressure measurement and interventions to lower blood pressure could benefit PLHIV on DTG-based ART. Further studies are needed to elucidate the mechanisms and reversibility of these changes after discontinuation of DTG."

Journal • Observational data • Cardiovascular • Human Immunodeficiency Virus • Hypertension • Hypotension • Infectious Disease

Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum (clinicaltrials.gov) - P=N/A | N=325 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Oct 2025 ➔ Mar 2026 | Trial primary completion date: Oct 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Open-Label Study Comparing Efficacy and Safety of ATV/RTV+3TC With ATV/RTV+TDF/FTC in HIV-Infected, Treatment Naïve Subjects, Followed by Treatment With ATV/RTV+3TC (clinicaltrials.gov) - P3 | N=3 | Terminated | Sponsor: Bristol-Myers Squibb | Phase classification: P3b ➔ P3

Phase classification • Human Immunodeficiency Virus • Infectious Disease • CD4