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lamivudine + zidovudine + abacavir (abacavir + Combivir / Combivir + abacavir / Trizivir)

✓ Approved

Shire · · Small Molecule

What is lamivudine + zidovudine + abacavir?

lamivudine + zidovudine + abacavir is a small molecule developed by Shire. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand Namesabacavir + Combivir, Combivir + abacavir, Trizivir
CompanyShire
Drug ClassSmall Molecule
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Shire

Mechanism of Action

Molecular Targets

lamivudine + zidovudine + abacavir acts on 1 molecular target:

gag-pol, HIV-1 (gag-pol)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

lamivudine + zidovudine + abacavir is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Infections and infestationsAcquired immunodeficiency syndrome✓ Approved

Related Research Articles

PubMedReproductive sciences (Thousand Oaks, Calif.)2026-10-09

TLD-Based Antiretroviral Therapy Compromises Ovarian Function and Reserve: Evidence from Experimental and Clinical Studies.

Ugwu Martha M, Bakare Airat A AA, Nafiu Tawakalitu T, Dosumu Olufunke O OO et al.

Combination antiretroviral therapy (cART) has improved human immunodeficiency virus (HIV) management, but long-term use is associated with reproductive dysfunction. This study investigated TLD (Tenofovir, Lamivudine and Dolutegravir)-based cART effects on ovarian function using animal models and exploratory clinical investigations in women living with HIV. In the animal study, female Wistar rats were randomized into control, TLD-based cART (22 mg/kg), and dolutegravir alone (2.5 mg/kg) groups, administered orally for 28 days. Estrous cycle, histology, oxidative stress, reproductive hormones, and ova count were assessed. Both TLD-based cART and dolutegravir significantly prolonged diestrus (p = 0.0083 and p = 0.0007, respectively) and reduced metestrus (p = 0.0057 and p = 0.0083, respectively). Treated groups showed significantly reduced ova counts (p = 0.0002 and 0.0003, respectively). Histology revealed structural alterations of the ovary, including atretic follicles, distorted stroma, and sparse theca cells. Additionally, treated groups showed increased malondialdehyde (p = 0.0421) and decreased glutathione (p = 0.0046) and catalase activities (p = 0.0411), indicating oxidative stress. Serum follicle-stimulating and luteinizing hormones were significantly reduced in both treated groups (FSH: p < 0.0001 and p = 0.0002; LH: p < 0.0001 and p = 0.0108, respectively). In the clinical investigation, serum anti-Müllerian hormone (AMH) levels were evaluated in HIV-positive women (n = 20) receiving TLD-based cART. Ten participants (50%) had AMH in low/very low categories ( < 1.0 ng/mL), while 11 (55%) had AMH below the normal reference range ( < 1.5 ng/mL). Menstrual interval and dysmenorrhea showed no significant changes. These preliminary findings suggest Dolutegravir and TLD-based cART may negatively affect female reproductive function by altering ovarian structure, hormonal balance, and ovarian reserve, potentially predisposing women living with HIV to fertility complications.

PMID 42850552
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PubMedDrug design, development and therapy2026-10-06

Novel Hybrid Scaffold of Pyrazole, Thiazole, and [1,2,3]triazole: Eco-Friendly Synthesis by DABCO, Anti-HIV-1 RT, and In Silico Studies.

Al-Saleem Muneera S M MSM, Elhenawy Ahmed A AA, Al Sharif Ohoud F OF, Riyadh Sayed M SM et al.

The emergence of drug-resistant HIV-1 strains and limitations of current reverse transcriptase (RT) inhibitors support the development of structurally novel antiviral scaffolds. Hybrid azole systems may provide complementary interactions within the HIV-1 RT binding pocket.Purpose: To synthesize novel pyrazole-thiazole-[1,2,3]triazole hybrids using an eco-friendly DABCO-mediated approach and evaluate their anti-HIV-1 RT activity and structure-activity relationships using experimental and computational methods. Fourteen hybrid compounds were synthesized from hydrazone-1-carbothioamide 3 through cyclo-condensation with hydrazonoyl chlorides 4a-j or 5a-d using DABCO, affording arylazo-thiazoles 6a-j and hydrazono-thiazol-4(5H)-ones 7a-d. Structures were characterized by IR, 1H-NMR, 13C-NMR, and mass spectrometry. Molecular docking against HIV-1 RT (PDB: 3V81) was used to prioritize candidates, and six compounds were evaluated using an ELISA-based RT inhibition assay with zidovudine as reference. DFT, molecular electrostatic potential, and intramolecular charge-transfer analyses were also performed. The target compounds were obtained in 90-95% yields. The six tested derivatives showed IC50 values of 0.192-1.693 μg/mL. Compound 7a was the most active (IC50 = 0.192 ± 0.008 μg/mL), with activity comparable to zidovudine (0.201 ± 0.009 μg/mL; p = 0.74), and showed the most favorable docking energy (-6.37 kcal/mol) with a key Lys65 hydrogen bond. The hydrazono-thiazolone series 7 generally outperformed series 6. DFT analysis associated higher hardness and wider HOMO-LUMO gaps with improved activity. Compound 7a represents a promising HIV-1 RT inhibitor lead, supported by consistent enzymatic, docking, and electronic-structure findings. Further cytotoxicity and cell-based antiviral studies are required to establish its selectivity and preclinical potential.

PMID 42834992
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PubMedJournal of hazardous materials2026-10-06

Stage-resolved attenuation of pharmaceutical mixture risk in a full-scale lagoon-wetland wastewater treatment system.

Gomes Marcelo Pedrosa MP, Marques Raizza Zorman RZ, de Paula Marques Nicole Geraldine NG, Leite Bárbara Zanicotti BZ et al.

Wastewater treatment performance is commonly evaluated based on contaminant removal, although environmental protection ultimately depends on reducing the cumulative ecological risk imposed by complex pharmaceutical mixtures. Here, we investigated the barrier-specific attenuation of estrogens, antidepressants, and antiretrovirals in a full-scale lagoon treatment system coupled to a pilot-scale constructed wetland by integrating repeated-measures ANOVA, barrier-specific log removal values (LRV), deterministic ecological risk assessment, and probabilistic mixture modeling using species sensitivity distributions (SSDs), and multisubstance potentially affected fraction (msPAF). Mean influent concentrations were 31.07 μg L⁻¹ for lamivudine and 322.75, 119.52, and 33.73 ng L⁻¹ for estrone, 17β-estradiol, and estriol, respectively. Pharmaceutical attenuation differed markedly among treatment barriers, with limited removal under anaerobic conditions and substantially greater attenuation during oxidative treatment and tertiary polishing. The constructed wetland provided the greatest incremental ecological protection, accounting for approximately 91.4% of the total cumulative deterministic ecological risk attenuation. Deterministic ecological risk identified efavirenz as the dominant contributor to cumulative long-term ecological risk, accounting for approximately 99.9% of the cumulative long-term deterministic risk throughout the wastewater treatment train. The short-term probabilistic mixture risk declined progressively from 0.651 in the influent to 0.602 after secondary treatment and was modeled as zero following tertiary wetland polishing. These findings demonstrate that wastewater treatment performance is more appropriately evaluated through barrier-specific ecological risk attenuation than concentration removal alone and highlight nature-based tertiary treatment as a highly effective strategy for mitigating pharmaceutical risks before environmental discharge.

PMID 42837922
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PubMedInfection2026-10-04

Integrated analysis of HIV-1 drug resistance across reverse transcriptase, protease and integrase in india: gene-region-corrected prevalence and threshold-specific scoring from public sequence data.

Das Amlan A, Patel Bhoomika B, Topiwala Alfeena A, Yadav Priyanshi P et al.

India carries the third-largest HIV-1 burden globally. The 2021 national transition to Tenofovir/Lamivudine/Dolutegravir (TLD) makes Integrase Strand Transfer Inhibitor resistance surveillance an urgent programmatic priority, yet no prior Indian study has simultaneously characterised all three pol gene regions using gene-region-corrected denominators or multi-threshold algorithmic scoring. We retrieved 4,375 HIV-1 subtype C pol sequences from LANL and NCBI GenBank (November 2024). Gene-region-specific denominators were applied (RT, n = 2,879; Protease, n = 2,373; Integrase, n = 1,084). Mutations were classified per 2022 IAS-USA criteria; drug-level resistance was scored across four Stanford HIVdb v9.4 thresholds with Benjamini-Hochberg FDR correction. Mutation co-occurrence was assessed across 231 pairs simultaneously. NNRTI resistance was 36.7% (95% CI: 35.0-38.5%), NRTI resistance 25.4%, and dual-class resistance 23.0%; predominant mutations were M184V (19.2%), K103N (11.9%), and Y181C (8.7%). Composite HIVdb scoring detected TDF resistance in 12.1% (≥ Level 3) - four-fold higher than K65R-based counting alone (3.0%) - reflecting Thymidine Analogue Mutation cross-resistance. Nevirapine, Efavirenz, and Protease Inhibitor major resistance were 32.9%, 31.7%, and 4.0%, respectively. INSTI major resistance was 1.6% (95% CI: 0.9-2.4%); Q148H/K/R was entirely absent, and Dolutegravir/Bictegravir resistance was 0% at ≥Level 3. L74M prevalence was 11.3% (9.5-13.3%). Threshold sensitivity reached 9.4-fold for etravirine; co-occurrence analysis identified K65R+V106M enrichment (8.4-fold, FDR q < 0.001). Among publicly available Indian sequences enriched for treatment-failure submissions, the complete absence of Q148-pathway mutations provides a bounded baseline among available pre-/early-TLD integrase sequences. The four-fold TDF resistance underestimation by conventional mutation counting and up to 9.4-fold threshold-dependent prevalence variation support composite algorithm-scored, threshold-specified reporting as a standard for database-level HIV drug resistance analyses.

PMID 42828625
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PubMedClinical pharmacology and therapeutics2026-10-03

Evaluating Vaginal Microbiome Effects on Antiretroviral Exposure in the Female Genital Tract Using Pharmacometric and Machine Learning Approaches.

Yan Diqin D, Collins Lindsey B LB, Staley Christopher C, Matovu Flavia Kiweewa FK et al.

Antiretroviral pre-exposure prophylaxis (PrEP) is less effective in women than expected, partly because drug exposure within the female genital tract is variable and may be influenced by the vaginal microbiome. We developed an integrated pharmacometrics and machine learning framework to evaluate associations between vaginal microbiome composition and cervical antiretroviral exposure in women with human immunodeficiency virus (HIV) receiving tenofovir (TFV)-, lamivudine (3TC)-, or emtricitabine (FTC)-containing regimens. Pharmacokinetic and microbiome data were obtained from two single-center studies in Uganda and the United States. Published population pharmacokinetic models were used to estimate individual parameters by maximum a posteriori Bayesian estimation and to simulate plasma and cervical tissue exposure metrics under sexual-activity-driven dosing that were not studied in these trials. Microbiome diversity was assessed using alpha and beta diversity analyses. Associations between microbial genera and cervical drug exposure were evaluated using correlation analysis, differential abundance testing, and three machine learning approaches: LASSO, random forest, and XGBoost. Overall vaginal microbiome diversity was not associated with cervical exposure to TFV, 3TC, or FTC. In contrast, specific taxa-level associations with cervical drug exposure were identified. For TFV, Gemella was positively associated with cervical TFV-diphosphate exposure, whereas Megasphaera and Falsiporphyromonas were negatively associated across multiple models. For 3TC, Dialister, Prevotella, Atopobium, Streptobacillus, and Gardnerella were repeatedly identified. For FTC, Bifidobacteriaceae was consistently selected, with Lachnospiraceae and Prevotellaceae also implicated. This pharmacometrics-machine learning framework identified specific vaginal taxa associated with cervical antiretroviral exposure, supporting the future development of microbiome-based biomarkers and precision PrEP strategies for women.

PMID 42827404
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PubMedAnnales pharmaceutiques francaises2026-10-01

In vitro and In vivo Evaluation of Freeze-Dried Vaginal Bigel of Dolutegravir and Lamivudine for HIV Pre-Exposure Prophylaxis.

Bhattacharyya Sayani S, Maddi Eswar Gupta EG

HIV remains a major global health concern, disproportionately affecting women. Use of conventional vaginal gels for prophylactic use is limited due to rapid clearance, poor retention and leakage. This study aims to develop and evaluate a novel mucoadhesive vaginal bigel delivering a fixed-dose combination of dolutegravir and lamivudine for enhanced prophylactic efficacy and user compliance. Bigels were formulated using hydrogel composed of gelatin-HPMC-hyaluronic acid and organogel of glyceryl monostearate in olive oil. Lamivudine was incorporated into the hydrogel phase, and dolutegravir was loaded into the organogel. Four formulations were prepared and were assessed for rheological properties and drug content. The best formulations were freeze-dried and evaluated for mucoadhesion, drug release in simulated vaginal and seminal fluids, cytotoxicity, apoptosis, and in vivo pharmacokinetics in rabbits. The best formulations demonstrated pseudoplastic viscoelastic behavior, high drug content (>80%), and sustained mucoadhesive retention for 24 h. Drug release exhibited biphasic kinetics, with rapid lamivudine release followed by sustained dolutegravir release. In vitro cell line studies showed enhanced apoptosis in HeLa cells with minimal toxicity in normal epithelial cells. In vivo pharmacokinetics confirmed prolonged vaginal drug levels above IC₅₀ thresholds, absence of mucosal irritation and subtherapeutic systemic exposure. Therefore, mucoadhesive freeze-dried bigels can provide a safe, effective, and patient-friendly platform for vaginal HIV pre-exposure prophylaxis, addressing key limitations of conventional gels and supporting user compliance.

PMID 42822646
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