Background: Uncertainty exists about the best treatment for people with HIV-1 who have virological failure with first-line combination antiretroviral therapy of a non-nucleoside analogue (NNRTI) plus two nucleoside or nucleotide analogue reverse transcriptase inhibitors (NtRTI). We compared a second-line regimen combining two new classes of drug with a WHO-recommended regimen.
Methods: We did this 96-week, phase 3b/4, randomised, open-label non-inferiority trial at 37 sites worldwide. Adults with HIV-1 who had confirmed virological failure (plasma viral load >500 copies per mL) after 24 weeks or more of first-line treatment were randomly assigned (1:1) to receive ritonavir-boosted lopinavir plus two or three NtRTIs (control group) or ritonavir-boosted lopinavir plus raltegravir (raltegravir group). The randomisation sequence was computer generated with block randomisation (block size four). Neither participants nor investigators were masked to allocation. The primary endpoint was the proportion of participants with plasma viral load less than 200 copies per mL at 48 weeks in the modified intention-to-treat population, with a non-inferiority margin of 12%. This study is registered with ClinicalTrials.gov, number NCT00931463.
Findings: We enrolled 558 patients, of whom 541 (271 in the control group, 270 in the raltegravir group) were included in the primary analysis. At 48 weeks, 219 (81%) patients in the control group compared with 223 (83%) in the raltegravir group met the primary endpoint (difference 1·8%, 95% CI -4·7 to 8·3), fulfilling the criterion for non-inferiority. 993 adverse events occurred in 271 participants in the control group versus 895 in 270 participants in the raltegravir group, the most common being gastrointestinal.
Interpretation: The raltegravir regimen was no less efficacious than the standard of care and was safe and well tolerated. This simple NtRTI-free treatment strategy might extend the successful public health approach to management of HIV by providing simple, easy to administer, effective, safe, and tolerable second-line combination antiretroviral therapy.
Funding: University of New South Wales, Merck, AbbVie, the Foundation for AIDS Research.
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http://dx.doi.org/10.1016/S0140-6736(13)61164-2 | DOI Listing |
BMC Infect Dis
December 2024
Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy.
Background: Ritonavir-boosted nirmatrelvir (N/r) is an antiviral which targets the main viral protease, administered to prevent the progression of SARS-CoV-2 infection in patients at high risk for severe COVID-19. We present a real-life case-control study evaluating the efficacy of N/r therapy in SARS-CoV-2 omicron variants positive outpatients in Campania region, Italy, with the aim of assessing the occurrence of three outcomes (hospital admission, admission in ICU and death) in cases and controls.
Methods: We enrolled SARS-CoV-2 positive subjects that came to our attention in Early antiviral treatment ambulatory of Infectious Diseases ward of University Federico II of Naples, Italy from January 1st, 2022, to December 31st, 2022, during the first five days from symptoms occurrence.
Vaccines (Basel)
October 2024
National Microbiology Center, Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain.
Background/objectives: The impact of virion maturation on neutralizing antibody responses in HIV treatment is not fully understood. This study examines whether antiretroviral regimens (ART) with boosted protease inhibitors (b-PI), which increase exposure to immature virions, affect neutralization capacity compared to Non-b-PI regimens.
Methods: Neutralization activity was assessed in 45 HIV-infected individuals on b-PI regimens and 56 on Non-b-PI regimens, adjusting for factors like infection duration, ART initiation, and immune markers.
Lancet HIV
June 2024
Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.
Background: Due to the low number of individuals with HIV-2, no randomised trials of HIV-2 treatment have ever been done. We hypothesised that a non-comparative study describing the outcomes of several antiretroviral therapy (ART) regimens in parallel groups would improve understanding of how differences between HIV-1 and HIV-2 might lead to different therapeutic approaches.
Methods: This pilot, phase 2, non-comparative, open-label, randomised controlled trial was done in Burkina Faso, Côte d'Ivoire, Senegal, and Togo.
Lancet HIV
February 2024
AMS-PHPT Research Collaboration, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand. Electronic address:
Background: Existing solid antiretroviral fixed-dose combination formulations are preferred over liquid formulations in children, but their suitability for neonates is unknown. We evaluated the pharmacokinetics and safety of paediatric abacavir-lamivudine fixed-dose dispersible tablets and ritonavir-boosted lopinavir granules in neonates.
Methods: In this open-label, two-stage, single-arm, phase 1/2, pharmacokinetic and safety trial, generic abacavir- lamivudine (120:60 mg) double-scored dispersible tablets and lopinavir boosted with ritonavir (40:10 mg) granules were studied.
J Antimicrob Chemother
February 2024
Department of Infectious Diseases, Fondazione PTV, University of Rome Tor Vergata, Rome, Italy.
Background: Maintenance monotherapy with ritonavir-boosted darunavir has yielded variable outcomes and is not recommended. Trial samples offer valuable opportunities for detailed studies. We analysed samples from a 48 week trial in Cameroon to obtain a detailed characterization of drug resistance.
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