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AIDS and Behavior May 2023Multiple factors may affect combined antiretroviral therapy (cART). We investigated the impact of food, beverages, dietary supplements, and alcohol on the... (Meta-Analysis)
Meta-Analysis Review
Multiple factors may affect combined antiretroviral therapy (cART). We investigated the impact of food, beverages, dietary supplements, and alcohol on the pharmacokinetic and pharmacodynamic parameters of 33 antiretroviral drugs. Systematic review in adherence to PRISMA guidelines was performed, with 109 reports of 120 studies included. For each drug, meta-analyses or qualitative analyses were conducted. We have found clinically significant interactions with food for more than half of antiretroviral agents. The following drugs should be taken with or immediately after the meal: tenofovir disoproxil, etravirine, rilpivirine, dolutegravir, elvitegravir, atazanavir, darunavir, lopinavir, nelfinavir, ritonavir, saquinavir. Didanosine, zalcitabine, zidovudine, efavirenz, amprenavir, fosamprenavir, and indinavir should be taken on an empty stomach for maximum patient benefit. Antiretroviral agents not mentioned above can be administered regardless of food. There is insufficient evidence available to make recommendations about consuming juice or alcohol with antiretroviral drugs. Resolving drug-food interactions may contribute to maximized cART effectiveness and safety.
Topics: Humans; HIV Infections; Ritonavir; Ethanol; Anti-Retroviral Agents; Beverages; Dietary Supplements; Anti-HIV Agents
PubMed: 36318429
DOI: 10.1007/s10461-022-03880-6 -
Annals of Medicine and Surgery (2012) Dec 2023The risk of falls in people living with HIV (PLHIVs) on antiretroviral therapy (ART) has received little attention in the literature. The aim of the meta-analysis is to... (Review)
Review
OBJECTIVE
The risk of falls in people living with HIV (PLHIVs) on antiretroviral therapy (ART) has received little attention in the literature. The aim of the meta-analysis is to quantify the association between fall risk and various categories of drugs used in ART.
MATERIAL AND METHODS
PubMed, Google Scholar, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched from inception to January 2023. Any observational study or controlled trial that reported on the relationship of at least one antiretroviral drug with falls in PLHIVs was included. Data on the frequency of single fallers, multiple fallers (≥2 falls), and non-fallers were extracted and studied for each drug and drug category. The pooled results were reported as an odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
A total of five observational studies (51 675 participants) were included out of 414 articles obtained through a literature review. Stavudine use was found to be associated with an increased risk of single falls in PLHIVs (OR: 1.69, 95% CI: 1.08-2.66, =0.02). However, efavirenz (OR: 0.82, 95% CI=0.76-0.89, <0.001) and zidovudine (OR: 0.82, 95% CI=0.77-0.92, <0.001) were found protective against the single falls. Didanosine had no significant association with fall risk (OR: 1.23, 95% CI: 0.78-1.93, =0.37). Likewise, protease inhibitors, integrase inhibitors, nucleoside reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors were discovered to have no significant association with fall risk.
CONCLUSION
Most drug categories of ART have no significant association with the risk of falls in PLHIVs. However, certain drugs, such as didanosine and stavudine, which have the inherent effect of causing balance deficits and neuropathy, should be used cautiously.
PubMed: 38098550
DOI: 10.1097/MS9.0000000000001411 -
World Journal of Hepatology Jan 2014To investigate the diagnosis, pathogenesis, natural history, and management of nodular regenerative hyperplasia (NRH) in patients with human immunodeficiency virus (HIV). (Review)
Review
AIM
To investigate the diagnosis, pathogenesis, natural history, and management of nodular regenerative hyperplasia (NRH) in patients with human immunodeficiency virus (HIV).
METHODS
We performed a systematic review of the medical literature regarding NRH in patients with HIV. Inclusion criteria include reports with biopsy proven NRH. We studied the clinical features of NRH, in particular, related to its presenting manifestation and laboratory values. Combinations of the following keywords were implemented: "nodular regenerative hyperplasia", "human immunodeficiency virus", "noncirrhotic portal hypertension", "idiopathic portal hypertension", "cryptogenic liver disease", "highly active antiretroviral therapy" and "didanosine". The bibliographies of these studies were subsequently searched for any additional relevant publications.
RESULTS
The clinical presentation of patients with NRH varies from patients being completely asymptomatic to the development of portal hypertension - namely esophageal variceal bleeding and ascites. Liver associated enzymes are generally normal and synthetic function well preserved. There is a strong association between the occurrence of NRH and the use of antiviral therapies such as didanosine. The management of NRH revolves around treating the manifestations of portal hypertension. The prognosis of NRH is generally good since liver function is preserved. A high index of suspicion is required to make a identify NRH.
CONCLUSION
The appropriate management of HIV-infected persons with suspected NRH is yet to be outlined. However, NRH is a clinically subtle condition that is difficult to diagnose, and it is important to be able to manage it according to the best available evidence.
PubMed: 24653794
DOI: 10.4254/wjh.v6.i1.55 -
Einstein (Sao Paulo, Brazil) 2014In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when... (Review)
Review
In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug-induced pancreatitis should always be considered in the diagnosis of patients with abdominal pain and elevated pancreatic enzymes.
Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Comorbidity; Female; Humans; Male; Pancreatitis; Risk Factors
PubMed: 24728257
DOI: 10.1590/s1679-45082014rw2561 -
The Cochrane Database of Systematic... 2000Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC). (Review)
Review
BACKGROUND
Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC).
OBJECTIVES
To assess the effects of zidovudine (AZT), zidovudine plus didanosine (ddI) and zidovudine plus zalcitabine (ddC) on HIV disease progression and survival.
SEARCH STRATEGY
Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts.
SELECTION CRITERIA
Randomised controlled trials comparing any two of AZT plus ddI, AZT plus ddC or AZT alone in participants with or without AIDS which collected information on deaths and new AIDS events.
DATA COLLECTION AND ANALYSIS
Individual patient data with, wherever possible, follow-up obtained beyond that previously published were obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials.
MAIN RESULTS
Six trials were included in the meta-analysis. During a median follow-up of 29 months, 2904 individuals progressed, of whom 1850 died. The addition of ddI to AZT delayed both progression (RR 0.74; 95% CI 0.67 to 0.82, P<0.0001) and death (RR 0.72; 95% CI 0.64 to 0.82, P<0.0001). Likewise, the addition of ddC to AZT also delayed progression (RR 0. 86; 95% CI 0.78 to 0.94, P=0.001) and death (RR 0.87; 95% CI 0.77 to 0.98, P=0.02). After 3 years the estimated percentages alive and without a new AIDS event were 53% for AZT+ddI, 49% for AZT+ddC and 44% for AZT alone; the percentages alive were 68%, 63% and 59% respectively. Five of the six trials involved randomised comparisons of AZT+ddI versus AZT+ddC: in these, the AZT+ddI regimen had greater effects on disease progression (P=0.004) and death (P=0.009).
REVIEWER'S CONCLUSIONS
The use of ddI and, to a lesser extent, ddC delayed both HIV disease progression and death, at least when added to AZT.
Topics: Adult; Anti-HIV Agents; Didanosine; Drug Administration Schedule; Drug Therapy, Combination; HIV Infections; Humans; Zalcitabine; Zidovudine
PubMed: 10796851
DOI: 10.1002/14651858.CD002038 -
Sexually Transmitted Infections Aug 2003To describe the clinical, epidemiological, and biochemical characteristics of published cases of lactic acidosis (LA) and to generate hypotheses concerning risk factors... (Review)
Review
OBJECTIVE
To describe the clinical, epidemiological, and biochemical characteristics of published cases of lactic acidosis (LA) and to generate hypotheses concerning risk factors associated with this complication.
METHODS
Systematic review of cases reported in the medical literature.
RESULTS
217 published cases were identified, 90 of which fulfilled the study definition and had sufficient individual data on potential risk factors to be included. The 90 patients had a mean age of 40.1 years (range 16-69) and 53% were female. All 90 patients were taking nucleoside reverse transcriptase inhibitors (NRTI) at the time of the episode. Among the 83 patients with details of their antiretroviral therapy (ART) regimen 51 patients were taking stavudine, 29 zidovudine, 27 didanosine, and 25 lamivudine. Around 50% of the patients had abdominal pain, nausea, or vomiting. Hepatic steatosis was consistently reported (53/90) and in 36 (68%) there was histological evidence. The case fatality rate was 48%. Six cases were rechallenged with NRTI and three developed a further LA episode. Using data on the numbers of HIV infected individuals receiving care in the United States, we estimate that the risk of LA could be 2.5 times higher for women than men.
CONCLUSIONS
NRTI use and female sex appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include duration of NRTI therapy, specific drug use, and genetic predisposition. A case-control study is needed to better define risk factors for severe LA.
Topics: Acidosis, Lactic; Adolescent; Adult; Aged; Anti-HIV Agents; Female; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Reverse Transcriptase Inhibitors; Risk Factors
PubMed: 12902594
DOI: 10.1136/sti.79.4.340 -
Clinical Infectious Diseases : An... Nov 2014Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality through sustained suppression of human... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality through sustained suppression of human immunodeficiency virus (HIV) replication and reconstitution of the immune response. Settings like China that experienced rapid HAART rollout and relatively limited drug selection face considerable challenges in controlling HIV drug resistance (DR).
METHODS
We conducted a systematic review and meta-analysis to describe trends in emergent HIV DR to first-line HAART among Chinese HIV-infected patients, as reflected in the point prevalence of HIV DR at key points and fixed intervals after treatment initiation, using data from cohort studies and cross-sectional studies respectively.
RESULTS
Pooled prevalence of HIV DR from longitudinal cohorts studies was 10.79% (95% confidence interval [CI], 5.85%-19.07%) after 12 months of HAART and 80.58% (95% CI, 76.6%-84.02%) after 72 months of HAART. The HIV DR prevalence from cross-sectional studies was measured in treatment intervals; during the 0-12-month HAART treatment interval, the pooled prevalence of HIV DR was 11.1% (95% CI, 7.49%-16.14%), which increased to 22.92% at 61-72 months (95% CI, 9.45%-45.86%). Stratified analyses showed that patients receiving a didanosine-based regimen had higher HIV DR prevalence than those not taking didanosine (15.82% vs 4.97%). Patients infected through former plasma donation and those receiving AIDS treatment at village clinics had higher HIV DR prevalence than those infected through sexual transmission or treated at a county-level hospital.
CONCLUSIONS
Our findings indicate higher prevalence of HIV DR for patients with longer cumulative HAART exposure, highlighting important subgroups for future HIV DR surveillance and control.
Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Asian People; China; Drug Resistance, Viral; HIV Infections; HIV-1; Humans; Prevalence
PubMed: 25053721
DOI: 10.1093/cid/ciu590 -
International Journal of Infectious... 2001Effective antiretroviral therapy remains beyond the reach of most human immunodeficiency virus (HIV)-infected persons living in the third world because of its tremendous... (Review)
Review
Effective antiretroviral therapy remains beyond the reach of most human immunodeficiency virus (HIV)-infected persons living in the third world because of its tremendous cost. The cancer drug, hydroxyurea, inhibits HIV-1 replication in vitro and, when combined with didanosine (ddI), results in significant antiretroviral synergy. In vivo, hydroxyurea specifically targets quiescent lymphocytes and macrophages, important cellular reservoirs for HIV-1, and the combination of ddI plus hydroxyurea effectively reduces plasma HIV-1 RNA levels. Combination ddI-hydroxyurea costs about one-eighth as much as currently recommended triple drug combinations, and several countries in Africa are exploring the feasibility of widescale use of ddI-hydroxyurea for their HIV-infected populations. Intrigued by its potential relevance for Africa, the authors reviewed the literature on the in vitro and clinical efficacy of ddI plus hydroxyurea against HIV. The combination of ddI plus hydroxyurea is an effective and potentially more affordable regimen for HIV-infected persons living in poorer countries.
Topics: Africa; Anti-HIV Agents; CD4 Lymphocyte Count; Didanosine; Drug Therapy, Combination; HIV Infections; Humans; Hydroxyurea; MEDLINE; Treatment Outcome; Viral Load; Zidovudine
PubMed: 11285159
DOI: 10.1016/s1201-9712(01)90048-7 -
The Canadian Journal of Hospital... Sep 2009Area under the concentration-time curve (AUC) is a pharmacokinetic parameter that represents overall exposure to a drug. For selected anti-infective agents,...
BACKGROUND
Area under the concentration-time curve (AUC) is a pharmacokinetic parameter that represents overall exposure to a drug. For selected anti-infective agents, pharmacokinetic-pharmacodynamic parameters, such as AUC/MIC (where MIC is the minimal inhibitory concentration), have been correlated with outcome in a few studies. A limited-sampling strategy may be used to estimate pharmacokinetic parameters such as AUC, without the frequent, costly, and inconvenient blood sampling that would be required to directly calculate the AUC.
OBJECTIVE
To discuss, by means of a systematic review, the strengths, limitations, and clinical implications of published studies involving a limited-sampling strategy for anti-infective agents and to propose improvements in methodology for future studies.
METHODS
The PubMed and EMBASE databases were searched using the terms "anti-infective agents", "limited sampling", "optimal sampling", "sparse sampling", "AUC monitoring", "abbreviated AUC", "abbreviated sampling", and "Bayesian". The reference lists of retrieved articles were searched manually. Included studies were classified according to modified criteria from the US Preventive Services Task Force.
RESULTS
Twenty studies met the inclusion criteria. Six of the studies (involving didanosine, zidovudine, nevirapine, ciprofloxacin, efavirenz, and nelfinavir) were classified as providing level I evidence, 4 studies (involving vancomycin, didanosine, lamivudine, and lopinavir-ritonavir) provided level II-1 evidence, 2 studies (involving saquinavir and ceftazidime) provided level II-2 evidence, and 8 studies (involving ciprofloxacin, nelfinavir, vancomycin, ceftazidime, ganciclovir, pyrazinamide, meropenem, and alpha interferon) provided level III evidence. All of the studies providing level I evidence used prospectively collected data and proper validation procedures with separate, randomly selected index and validation groups. However, most of the included studies did not provide an adequate description of the methods or the characteristics of included patients, which limited their generalizability.
CONCLUSIONS
Many limited-sampling strategies have been developed for anti-infective agents that do not have a clearly established link between AUC and clinical outcomes in humans. Future studies should first determine if there is an association between AUC monitoring and clinical outcomes. Thereafter, it may be worthwhile to prospectively develop and validate a limited-sampling strategy for the particular anti-infective agent in a similar population.
PubMed: 22478922
DOI: 10.4212/cjhp.v62i5.827