abacavir/lamivudine/lopinavir/ritonavir (ABC/3TC/LPV/r) / Cipla, DNDi - LARVOL DELTA

Infants With HIV Starting ART Within 4 Months of Age Can Achieve Sustained Undetectable HIV-1 DNA (CROI 2025) - "They all received PMTCT and treatment with the standard of care schedule at their country, which was abacavir, lamivudine and lopinavir/ritonavir. Conclusions Children with ART started within 4 months of life and immediately after diagnosis as per standard of care in SSA can achieve sustained undetectable HIV-1 DNA, VL and high CD4, similar to children treated in the first 48 hours of life. Children with these features may have a greater likelihood of ART-free viral control and represent ideal candidates for future analytical treatment interruption trials targeting HIV cure."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease • CD4

Pediatric Dolutegravir Optimization: 18 month follow up of viral load suppression (AIDS 2024) - "Majority (99%) were transitioned from ABC/3TC/LPV/r to a pDTG based regimen, 251 to ABC/3TC/LPV/r and 4 to AZT/3TC/LPV/r based on genotype results. Many children have benefited from the introduction of pDTG, however improvement in viral suppression observed was not statistically significant. Some of our youngest clients still struggle with adherence despite improved formulations. Focus must still be on improving this group through innovative programming."

Clinical • Pediatrics

CMV RETINITIS IN ADVANCED HIV DISEASE - THE IMPORTANCE OF FUNDUS EXAMINATION. (ESPID 2024) - "She was found to have maternally transmitted HIV 1 and initiated on ART with Abacavir + Lamivudine + Lopinavir/ ritonavir...IV Piperacillin – Tazobactum and Metronidazole were given for 3 weeks and later switched to oral Amoxiciliin - clavulanate...She was initiated on IV Ganciclovir and later switched to oral Valganciclovir for a total of 3 months with complete resolution of the retinitis, liver abscesses, weight gain and rise in CD4 count to 119 cells/cumm. Learning Points/Discussion . Unmasking CMV IRIS can present after initiation of ART emphasizing the importance for fundus examination."

Metastases • Candidiasis • Cognitive Disorders • Genetic Disorders • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Ocular Inflammation • Ophthalmology • Pain • Pneumonia • Respiratory Diseases • Retinal Disorders • CD4

1 in 5 Sub-Saharan Infants Switches From Undetectable to Detectable HIV Viral Load During Follow-Up (CROI 2024) - "The most common starting ART regimen was Lamivudine + Abacavir + Lopinavir/ritonavir in 140/215 (65%), 10% switched to DTG in 2021. Undetectable VL increased across time, but oscillations between undetectable and detectable VL in the long term were frequent. This underscores the need for further investigations to assess the potential clinical implications of these fluctuations on patient outcomes and the size of the viral reservoir."

Human Immunodeficiency Virus • Infectious Disease

Improved virologic suppression in children living with HIV under the age of 5 in Tanzania after the initiation of a viremia clinic and pediatric dolutegravir (IAS-HIV 2023) - "Per national guidelines, the first-line ART regimen for children <20kg was abacavir-lamivudine-lopinavir/ritonavir (ABC-3TC-LPV/r) and dolutegravir (DTG) 50mg could be used if =20kg. Despite historical challenges in <5, we saw sustained improvements in VS rates that improved after the initiation of a Viremia Clinic and pediatric DTG. Moreover, clinic-wide rates of VS have begun to improve, though less dramatically than in <5."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Viral load suppression in children living with HIV after pediatric dolutegravir optimization in Eswatini (IAS-HIV 2023) - "Before optimization, 95% were on ABC/3TC/LPV/r (212/224); after optimization, 97% were on ABC/3TC/DTG (219/224). Children have benefited from introduction of pDTG. All children have seen improved viral suppression , but the 12-23 months age group and new initiations still struggle to meet national targets. Pending viral load data will continue to be tracked and evidence generated will be shared over the coming years."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Dolutegravir in our youngest cohort: follow-up of genotype led antiretroviral optimization in unsuppressed children (IAS-HIV 2023) - " Thirty clients on first line ABC-3TC-LPV/r (abacavir, lamivudine, lopinavir/ritonavir) with viral loads > 1,000 copies/mL were genotyped. Our cohort demonstrates high re-suppression rates with the introduction of pDTG despite still struggling to reach national suppression targets. However, high level ABC resistance does exist in this young cohort, confirming that in resource limited settings without genotype guidance, some children are being placed on regimens that are not fully active. It is unknown if this is a safe and durable strategy."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Acceptability of a new 4-in-1 Abacavir/Lamivudine/Lopinavir/Ritonavir paediatric fixed-dose combination: the caregiver-child dyads' perspective. (PubMed, Ther Adv Infect Dis) - P1/2 | "These findings informed further practical recommendations. Clinical trial number: NCT03836833."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Pharmacokinetics and Dose Optimization Strategies of Para-Aminosalicylic Acid in Children with Rifampicin-Resistant Tuberculosis. (PubMed, Antimicrob Agents Chemother) - "Increased PAS clearance was observed in both pharmacokinetic profiles from the only patient receiving efavirenz. No effect of renal function, sex, ethnicity, nutritional status, HIV status, antiretrovirals (lamivudine, abacavir, and lopinavir-ritonavir), or RR-TB drugs was detected...A transit compartment adequately describes absorption for the slow-release PAS formulation. Children should be dosed at the higher range of current WHO-recommended PAS doses and in a once-daily dose to optimize treatment."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Pharmacokinetics and safety of the abacavir/lamivudine/lopinavir/ritonavir fixed-dose granule formulation (4-in-1) in neonates: PETITE study. (PubMed, J Acquir Immune Defic Syndr) - "The high mg/kg abacavir and lamivudine doses and AUCs were safe, and the formulation well tolerated; however, lopinavir/ritonavir exposures were extremely low, preventing its use in neonates. Alternative paediatric solid antiretroviral formulations must be studied in neonates."

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

[VIRTUAL] Pharmacokinetics, safety and acceptability of a single dose of abacavir/lamivudine/lopinavir/ritonavir (4-in-1) fixed-dose granule formulation in neonates: PETITE study (IAS-HIV 2021) - "The high mg/kg ABC and 3TC doses imposed by the 4-in-1 in neonates were safe following a single dose, but LPV/r exposures were extremely low. Significant LPV/r dose increases would be required to achieve therapeutic LPV exposures, unduly increasing ABC/3TC exposures, and thereby preventing use of the 4-in-1 in neonates. Other pediatric solid formulations of LPV/r and ABC/3TC that allow different drug ratios should be studied in neonates."

Clinical • Late-breaking abstract • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

A new strawberry-flavoured HIV treatment for children could improve adherence (Health-e) - "A new paediatric HIV treatment could be a breakthrough for parents struggling to administer medication for their young children. The treatment, created by Cipla, in partnership with Drugs for Neglected Diseases Initiative (DNDi), could improve children’s adherence to antiretroviral treatment. The drug is a fixed-dose four-in-one combination of abacavir, lamivudine, lopinavir, ritonavir for infants and children under the age of three....The South African Health Products Regulatory Authority has also approved the medication, says Cipla....'The treatment is specially made for children aged 0–14 years living with HIV with little or no access to treatment'..."

Launch non-US • Non-US regulatory • Human Immunodeficiency Virus

[VIRTUAL] Small Airway Disease and Brochodilator Response in Children with HIV in Sub Saharan Africa (ATS-I 2020) - "The study participants were on a combination of either Abacavir, Lamivudine, Lopinavir Ritonavir, Zidovudine or Nevirapine. The mean z scores for all acceptable spirometry were: %FEV/FVC 82%; FEV: pre BDR zFEV1 -2.27, postBDR zFEV1 -2.03; % change postBDR 4.28%; least changes in FVC: pre BDR zFVC -1,92 post BDR zFVC -1,88; % change post BDR 0.62%; with significant changes in FEF 25-75: pre BDR zFEF 25-75 -1.63; post BDR zFEF 25-75 -1,14; % change post BDR 21.07% CONCLUSIONS. Spirometric values of FEF 25-75 BDR is useful to diagnose SAD in children and helps identify children that require long term follow-up of their lung function."

Clinical • Asthma • Chronic Obstructive Pulmonary Disease • Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases

Drug resistance mutations among South African children living with HIV on WHO-recommended ART regimens. (PubMed, Clin Infect Dis) - "High levels of NNRTI and NRTI DRMs among CLHIV receiving ABC/3TC/LPV/r suggests a lasting impact of failed PMTCT interventions on DRMs. However, drug susceptibility analysis, reveals that CLHIV with detectable viremia on ABC/3TC/LPV/r are more likely to have maintained at least two effective agents on their current HIV regimen than those on ABC/3TC/EFV."

Clinical • Journal • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

[VIRTUAL] The clinical and economic impact of genotypic resistance testing after virologic failure on first-line tenofovir-lamivudine-dolutegravir in South Africa (AIDS 2020) - " We used the CEPAC-International model to compare four strategies among adults with VF on TLD after EAC: 1) “GRT” to distinguish people with susceptible virus (VFS) who continue TLD from people with dolutegravir-resistant virus (VFR), who switch to second-line ART (LPV/r+AZT/3TC); 2) “Immediate switch” to second-line; 3) “EAC+,” additional EAC while continuing TLD with switch to second-line for anyone with persistent VF at 6 m; 4) “TLD,” remaining on TLD indefinitely. A strategy offering genotypic resistance testing after virologic failure on TLD resulted in the best clinical outcomes at lower cost than EAC+ or Immediate switch and was cost-effective versus TLD at lower genotype cost (≤$60) or ≥ 5% dolutegravir resistance. Scaling up capacity for genotype in resource-limited settings is a rational addition to TLD rollout."

Clinical • HEOR • Infectious Disease

Small Airway Disease and Brochodialator Response in Children with HIV in Sub Saharan Africa (ATS 2020) - "The study participants were on a combination of either Abacavir, Lamivudine, Lopinavir Ritonavir, Zidovudine or Nevirapine. The mean z scores for all acceptable spirometry were: %FEV/FVC 82%; FEV: pre BDR zFEV1 -2.27, postBDR zFEV1 -2.03; % change postBDR 4.28%; least changes in FVC: pre BDR zFVC -1,92 post BDR zFVC -1,88; % change post BDR 0.62%; with significant changes in FEF 25-75: pre BDR zFEF 25-75 -1.63; post BDR zFEF 25-75 -1,14; % change post BDR 21.07%CONCLUSIONS.Spirometric values of FEF 25-75 BDR is useful to diagnose SAD in children and helps identify children that require long term follow-up of their lung function."

Clinical

Second-line antiretroviral therapy failure and characterization of HIV-1 drug resistance patterns in children in Mali. (PubMed, Arch Pediatr) - "This study demonstrated that LPV/r remains active in most patients after second-line ART failure. In children whose second-line ART fails, particular attention should be paid to their ART and adherence history when considering the next treatment option."

Clinical • Journal