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.

Previous studies have reported an association of proton pump inhibitor (PPI) use and decreased sustained viral response rate (SVR) in patients taking ledipasvir/sofosbuvir (LDV/SOF). The relationship between PPI usage and SVR is less clear in patients with HIV/HCV coinfection, where concomitant antiretrovirals may result in more complex drug interactions. This retrospective study evaluates the effects of acid suppression medications (PPI or H₂ -receptor antagonist [H₂ B]) use and SVR rates in patients with HIV/HCV or HCV and taking LDV/SOF in a large multicentre veteran cohort. Patients in the Veterans Affairs Health Care System who received LDV/SOF ± ribavirin from 10/10/2014 to 12/31/2015 were included. The odds ratios (OR) of PPI or H₂ B use for SVR were adjusted for clinical factors and with inverse probability of treatment weighting for non-random treatment selection for acid suppression medication use. There were 9703 veterans included in our final analysis. After adjustment of other clinical factors, PPI use is associated with a lower SVR in the overall cohort (95.0% vs. 96.1%, OR: 0.86, 95% CI: 0.74-0.99, p = .03, number needed to harm 90.9) and HIV/HCV coinfection subgroup (93.4% vs. 96.9%, OR: 0.47, 95% CI: 0.26-0.85, p = .01, number needed to harm 28.6). This present study reveals PPI use is associated with reduced SVR after LDV/SOF treatment, with a more significant impact in the subgroup of patients with HIV/HCV coinfection. Precautions need to be taken when using PPI and LDV/SOF in this group of patients.

The release and absorption profile of an oral medication is influenced by the physicochemical properties of the drug and its formulation, as well as by the anatomy and physiology of the gastrointestinal (GI) tract. During drug development the bioavailability of a new drug is typically assessed in early clinical studies in a healthy adult population. However, many disease conditions are associated with an alteration of the anatomy and/or physiology of the GI tract. The same holds true for some subpopulations, such as paediatric or elderly patients, or populations with different ethnicity. The variation in GI tract conditions compared to healthy adults can directly affect the kinetics of drug absorption, and thus, safety and efficacy of an oral medication. This review provides an overview of GI tract properties in special populations compared to healthy adults and discusses how drug absorption is affected by these conditions. Particular focus is directed towards non-disease dependent conditions (age, sex, ethnicity, genetic factors, obesity, pregnancy), GI diseases (ulcerative colitis and Crohn's disease, celiac disease, cancer in the GI tract, Roux-en-Y gastric bypass, lactose intolerance, Helicobacter pylori infection, and infectious diseases of the GI tract), as well as systemic diseases that change the GI tract conditions (cystic fibrosis, diabetes, Parkinson's disease, HIV enteropathy, and critical illness). The current knowledge about GI conditions in special populations and their impact on drug absorption is still limited. Further research is required to improve confidence in pharmacokinetic predictions and dosing recommendations in the targeted patient population, and thus to ensure safe and effective drug therapies.

HIV and Helicobacter pylori are common chronic infections in sub-Saharan Africa. Both conditions can predispose to gastric hypochlorhydria that may be a risk factor for enteric infections and reduced drug absorption. We have investigated to what extent HIV and H. pylori infections are associated with hypochlorhydria in a Malawian cohort of patients undergoing endoscopy.

104 sequential symptomatic adults referred for gastroscopy at Queen Elizabeth Central Hospital, Blantyre, Malawi, had blood taken for rapid HIV testing and fasting serum gastrin analysis. Gastric fluid was aspirated for pH testing, and gastric biopsies were taken.

After 9/104 HIV-infected patients who were already established on anti-retroviral therapy were excluded, 17/95 (25.0%) were seropositive for untreated HIV, and 68/95 (71.6%) patients were H. pylori positive by histology. Hypochlorhydria (fasting gastric pH>4.0) was present in 55.8% (53/95) of patients. H. pylori infection was significantly associated with hypochlorhydria (OR 2.91, [1.02-7.75], p=0.046). While single infection with HIV was not significantly independently associated with hypochlorhydria. H. pylori and HIV co-infection was more strongly associated with hypochlorhydria (OR 6.25, [1.33-29.43], p=0.020) than either infection alone, suggesting an additive effect of co-infection. HIV infection was associated with higher serum gastrin levels (91.3 pM vs. 53.1 pM, p=0.040), while H. pylori infection was not (63.1 pM vs. 55.1 pM, p=0.610). Irrespective of H. pylori and HIV status, most patients (>90%) exhibited pangastritis. Only three patients had histological evidence of gastric atrophy, of which only one was HIV-infected.

H. pylori infection was associated with fasting hypochlorhydria, while HIV was not independently associated. HIV and H. pylori co-infection, however, was more strongly associated with hypochlorhydria than H. pylori infection alone. The mechanism of this apparent additive effect between HIV and H. pylori remains unclear, but appears to be related to chronic pangastritis rather than gastric atrophy, and associated with hypergastrinaemia in HIV-infected individuals.

Drug absorption represents an important factor affecting the efficacy of oral drug treatment. Gastric secretion and motility seem to be critical for drug absorption. A causal relationship between impaired absorption of orally administered drugs and Helicobacter pylori (H. pylori) infection has been proposed. Associations have been reported between poor bioavailability of l-thyroxine and l-dopa and H. pylori infection. According to the Maastricht Florence Consensus Report on the management of H. pylori infection, H. pylori treatment improves the bioavailability of both these drugs, whereas the direct clinical benefits to patients still await to be established. Less strong seems the association between H. pylori infection and other drugs malabsorption, such as delavirdine and ketoconazole. The exact mechanisms forming the basis of the relationship between H. pylori infection and impaired drugs absorption and/or bioavailability are not fully elucidated. H. pylori infection may trigger a chronic inflammation of the gastric mucosa, and impaired gastric acid secretion often follows. The reduction of acid secretion closely relates with the wideness and the severity of the damage and may affect drug absorption. This minireview focuses on the evidence of H. pylori infection associated with impaired drug absorption.

Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs.

To focus on the evidence of impaired drug absorption associated with H. pylori infection.

Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted.

In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication.

A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.

Gastroesophageal reflux disease and other related symptoms are common comorbidities for HIV-infected patients. Therefore, concurrent use of proton pump inhibitors and antiretrovirals is a common practice in the clinical setting. However, this practice may alter antiretroviral pharmacokinetics and lead to treatment failure due to inadequate drug exposure. Clinician awareness of these complex interactions is essential for optimal HIV management. This review summarizes the current knowledge on the interactions between proton pump inhibitors and antiretrovirals, and makes recommendations for the coadministration of proton pump inhibitors.

To determine whether the pharmacokinetics of atazanavir, a protease inhibitor used to treat human immunodeficiency virus (HIV) infection, are altered by its coadministration with lansoprazole, a proton pump inhibitor.

Single-dose, open-label, complete-crossover study.

Clinical research center.

Ten healthy adult volunteers.

In phase A, subjects received a single oral dose of atazanavir 400 mg alone. In phase B, the same subjects received oral lansoprazole 60 mg, and after 24 hours they were given a second dose of oral lansoprazole 60 mg with atazanavir 400 mg. Eleven blood samples were collected from each subject over a 24-hour period for determination of atazanavir plasma concentrations by a validated high-performance liquid chromatography assay. Pharmacokinetic analysis was performed by standard noncompartmental methods. Nine subjects completed the study, and no significant adverse events were reported. Absorption of atazanavir was significantly reduced when it was coadministered with lansoprazole, as evidenced by a 94% decline in mean area under the concentration-time curve during the 24 hours after administration (AUC(0-24)) (p<0.01). The mean +/- SD AUC(0-24) for phase A was 16.3 +/- 9.0 microM x hour versus 0.95 +/- 1.8 microM x hour for phase B (p<0.01). The mean +/- SD maximum concentration of atazanavir was 3.2 +/- 1.7 microM for phase A and 0.13 +/- 0.19 microM for phase B (p<0.01).

Acid suppression markedly reduced the bioavailability of atazanavir in this group of healthy volunteers. Based on these results, atazanavir should not be coadministered with lansoprazole or other proton pump inhibitors.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a diverse group of compounds that inhibit HIV Type 1 reverse transcriptase. Although possessing a common mechanism of action, the approved NNRTIs, delavirdine, efavirenz and nevirapine, differ in structural and pharmacokinetic characteristics. Each of the NNRTIs undergoes biotransformation by the cytochrome P450 (CYP) enzyme system, thus making them prone to clinically significant drug interactions when combined with other antiretrovirals. In addition, they interact with other concurrent medications and complementary/alternative medicines, acting as either inducers or inhibitors of drug-metabolising CYP enzymes. These drug interactions become an important consideration in the clinical use of these agents when designing combination regimens, as recommended by current guidelines. This review provides an updated summary of pharmacokinetic interactions with NNRTIs.

Infection with the human immunodeficiency virus (HIV) and the development of acquired immunodeficiency syndrome (AIDS) have had a significant impact on domestic and global health, social, political, and economic outcomes. Prevention and treatment efforts to control HIV infection are more demanding than in previous decades. Achieving food and nutrition security, and managing nutrition-related complications of HIV infection and the multiple aspects of disease initiated by or surrounding HIV infection, referred to as HIV disease, remain challenges for patients and for those involved with HIV/AIDS prevention, care, and treatment efforts. Confounding clinical issues include medication interactions, coinfection with other infections and diseases, wasting, lipodystrophy, and others. Dietetics professionals, other health care professionals, and people infected with HIV will need to understand and address multiple complex aspects of HIV infection and treatment to improve survival, body functions, and overall quality of life. Individualized nutrition care plans will be an essential feature of the medical management of persons with HIV infection and AIDS.