Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Jordan, Rachel; Gold, Lisa; Cummins, Carole; Hyde, Chris

doi:10.1136/bmj.324.7340.757

Cited by 77 publications

(40 citation statements)

References 73 publications

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“…To our knowledge, so far, very little information is available about the response to treatment of patients with very high pre-HAART viraemia (>500,000 copies/ ml) [30][31][32][33][34]. The current definition of high viral load is >100,000 copies/ml, and nearly all studies, and guidelines, tend to adapt their analyses and statements to this threshold [2,6,12,[17][18][19][20][21].…”

Section: Discussionmentioning

confidence: 99%

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

et al. 2013

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Background: We tested whether pre-HAART viraemia affects the achievement and maintenance of virological success in HIV-1-infected patients starting modern firstline therapies. Methods: A total of 1,430 patients starting their first HAART (genotype-tailored) in 2008 (median; IQR: 2006-2009) were grouped according to levels of pre-HAART viraemia (≤30,000, 30,001-100,000, 100,001-300,000, 300,001-500,000 and >500,000 copies/ml). The impact of pre-therapy viraemia on the time to virological success (viraemia ≤50 copies/ml) and on the time to virological rebound (first of two consecutive viraemia values >50 copies/ml after virological success) were evaluated by Kaplan-Meier curves and Cox regression analyses. Results: Median pre-HAART viraemia was 5.1 log 10 copies/ml (IQR 4.5-5.5), and 53% of patients had viraemia >100,000 copies/ml. By week 48, the prevalence of patients reaching virological success was >90% in all pre-HAART viraemia ranges, with the only exception of range >500,000 copies/ml (virological success =83%; P<0.001). Higher pre-HAART viraemia was tightly correlated with longer median time to achieve virological success. Cox multivariable estimates confirmed this result: patients with pre-HAART viraemia >500,000 copies/ml showed the lowest hazard of virological undetectability after adjusting for age, gender, pre-HAART CD4 + T-cell count, transmitted drug resistance, calendar year and third drug administered (adjusted hazard ratio [95% CI]: 0.27 [0.21, 0.35]; P<0.001). Pre-HAART viraemia >500,000 copies/ml was also associated with higher probability of virological rebound compared with patients belonging to lower viraemia strata at weeks 4, 12 and 24 (P=0.050). Conclusions: At the time of modern HAART, and even though an average >90% of virological success, high pre-HAART viraemia remains an independent factor associated with delayed and decreased virological success. Patients starting HAART with >500,000 copies/ml represent a significant population that may deserve special attention.HAART has significantly extended the time to development of AIDS and to death in HIV-infected individuals [1,2]. Its efficacy in suppression of plasma HIV-1 RNA to undetectable levels, and in increasing CD4 + T-cell count, is well documented in several clinical trials [3][4][5][6].Despite years of great progress in treating AIDS, however, in some patients starting their first treatment; the effectiveness of HAART is still not sufficient, with consequent virological failures [7][8][9]. These failures can be caused by several factors, such as drug potency, drug

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Section: Discussionmentioning

confidence: 99%

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

et al. 2013

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“…5 This strategy evolved from the recognition that treatment of chronic HIV infection with only one or two ARV drugs may result in rapid treatment failure and the development of resistance to the ARV drugs, which may compromise future therapeutic options. 5,6 About a quarter of patients on ART discontinued the treatment within the first eight months due to treatment failure, adverse drug toxicity or non-compliance with the therapy. 7,8 There is also abundant evidence indicating that treatment success is dependent on adherence to ARV drugs.…”

Section: Introductionmentioning

confidence: 99%

Pharmacoepidemiology of antiretroviral drugs in a teaching hospital in Lagos, Nigeria

Ia¹,

So²,

Olayemi³

et al. 2015

Ghana Medical Journal

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SUMMARYObjective: Prescribing, adherence, and adverse drug events to HAART in a large antiretroviral programme in Lagos was evaluated. Design A retrospective 5 year open cohort study Setting The AIDS Prevention Initiative in Nigeria (APIN) clinic at LUTH is one of the United States Presidential Emergency Plan for AIDS Relief (PEP-FAR) funded centers for HIV relief program in Nigeria Participants The case files of 390 patients on HAART and attending the APIN clinic were reviewed sequel to random selection. Main outcome measures: Demographics of the patients and pattern of antiretroviral (ARV) combination drugs prescribed were extracted from their case files. The details of the adverse drug events (ADEs) were extracted from drug toxicity forms regularly filled for each patient. A Chi-square test with Yates correction was used to determine the association between adherence and therapeutic outcome Results A total of 2944 prescriptions were assessed. Zidovudine + lamivudine + nevirapine (35.87%) and stavudine + lamivudine + nevirapine (35.63%) were the most frequently prescribed combinations. Over 2000 ADEs were reported with cough (13.3%), fever (8.75%) and skin rashes (8.01%) being the most frequently reported. Drug adherence was associated with good therapeutic outcome (χ2 = 115.60, p<0.0001). Conclusions: Zidovudine + lamivudine + nevirapine was the most frequently prescribed ARV combination. Cough was the most frequently reported ADE. Interventions aimed at rational prescribing of ARV drugs and improving adherence to antiretroviral drugs is essential for good therapeutic outcome in the treatment of HIV infection.

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“…This strategy evolved from the recognition that continual treatment of HIV infection with only one or two ARV agents would typically result in rapid treatment failure and development of ARV resistance which may compromise future therapeutic options [4,5].…”

Section: Introductionmentioning

confidence: 99%

Adverse Events in HIV- infected Children on Antiretroviral Therapy at a Teaching Hospital in Lagos, Nigeria: A Retrospective Study

Oshikoya¹

2012

Adv Pharmacoepidem Drug Safety

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Background: Highly active antiretroviral therapy (HAART) program requires adequate monitoring of the potential adverse events to the antiretroviral (ARV) drugs. We investigated the ARV drug combinations prescribed for HIV-infected children and their suspected adverse events.Methods: This is a retrospective and descriptive study involving HIV-infected children less than 15 years old who received treatment at the APIN clinic, Lagos University Teaching Hospital (LUTH) in Nigeria. The case files of 80 patients initiated on HAART, between January 2008 and December 2009, were reviewed. Their demographics, clinical details and medication use, the prescribed HAART regimen, and the suspected clinical and laboratory adverse events were extracted. Results:The patients were female (46; 57.5%) preponderant with a median age of 3 (IQR: 1.1-6.0) years. Zidovudine-lamivudine-nevirapine (AZT-3TC-NVP) combination (74; 92.5%) was the most frequently prescribed first-line regimen. Thirty three patients changed their first-line HAART to abacavir-lamivudine-lopinavir boosted with ritonavir (ABC-3TC-LVP/r) (11; 33.3%), and zidovudine-lamivudine-abacavir-lopinavir boosted with ritonavir (AZT-3TC-ABC-LVP/r) (8; 24.2%) combinations. Of the 80 patients included in the study, 38(47.7%) experienced 142 adverse events. The most frequently experienced clinical adverse events were nevirapine-induced skin rashes (93; 65.5%), vomiting (19; 13.4%), and pallor (12; 8.5%). Macrocytosis (22/72; 30.6%), anaemia (6/72; 8.3%), and thrombocytopenia (2/72; 2.8%) were the commonest haematological adverse events associated with zidovudine. Conclusions:The HAART regimens used for HIV-infected children in this study have a good safety profile. Their few adverse events suggest a need for prospective pharmacovigilance to effectively monitor the toxicities of ARV drugs.

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Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Cited by 77 publications

References 73 publications

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

Pharmacoepidemiology of antiretroviral drugs in a teaching hospital in Lagos, Nigeria

Adverse Events in HIV- infected Children on Antiretroviral Therapy at a Teaching Hospital in Lagos, Nigeria: A Retrospective Study

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