Treatment Of HIV-1 Infection In Adults Research Articles

The effect of dolutegravir on the pharmacokinetics of metformin in healthy subjects.

Introduction Dolutegravir (DTG) is an HIV integrase strand transfer inhibitor approved for use in combination with other antiretrovirals for the treatment of HIV-infection in adults and adolescents. Metformin is a drug frequently used in diabetic HIV-infected patients, which requires titration to optimize dosing. In vitro, DTG inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE 1) which are known to be involved in the disposition of metformin. The objective of this study was to assess the drug interaction between DTG and metformin.Materials and Methods This was an open-label, parallel-group, three-period crossover study in healthy adult subjects. Eligible subjects were enrolled into one of the two treatment cohorts (15 subjects/cohort). Subjects received metformin 500 mg q12h for 5 days in Period 1; metformin 500 mg q12h plus DTG 50 mg q24h (Cohort 1) or 50 mg q12h (Cohort 2) for 7 days in Period 2; and metformin 500 mg q12h for 10 days in Period 3. There were no washout periods between treatments. All doses of study drug were taken with a moderate-fat meal. Serial plasma PK samples and safety assessments were obtained throughout the study. Non-compartmental PK analysis was performed and geometric least squares (GLS) mean ratios and 90% confidence intervals (CI) were generated by the mixed effect model for within-subject treatment comparisons for each cohort.Results Fourteen and thirteen subjects completed study in Cohort 1 and Cohort 2, respectively. Plasma exposures of metformin were significantly increased when co-administered with DTG (Table 1).There were no apparent changes in metformin half-life and tmax. Increased metformin plasma exposure returned to normal levels observed in Period 1 after DTG was discontinued in Period 3. No Grade 3 or 4 adverse events (AEs), deaths or serious AEs were reported during the study. Most frequently reported drug-related AEs were headache (9), loose stools (8), and nausea (7). All AEs were mild or Grade 1 with the exception of one Grade 2 headache.Conclusions Co-administration of DTG and metformin was well tolerated, yet significantly increased metformin plasma exposure; effects were DTG dose dependent. Though metformin has a wide therapeutic index and alone is not associated with hypoglycemia, close monitoring is recommended when co-administering metformin and DTG. Dose adjustments of metformin may be considered.

Antiretroviral treatment of adult HIV infection: 2014 Recommendations of the International Antiviral Society-USA panel

Antiretroviral treatment of adult HIV infection: 2014 Recommendations of the International Antiviral Society-USA panel

Learning from drug changes in antiretroviral therapy

In middle 1990s, the availability of nucleoside analog and non-nucleoside analog inhibitors of the HIV reverse transcriptase (NRTI and NNRTI, respectively) and inhibitors of viral protease (PIs) allowed for the introduction of treatments combining different families of antiretrovirals. This approach was defined as HAART and is currently known as Combined Antiretroviral Therapy (cART). Initial cART combinations included three drugs (two NRTI and a PI or NNRTI) and achieved a durable reduction of HIV replication in HIVinfected patients, resulting in a sharp reduction in AIDSrelated deaths and opening a new era in HIV treatment.

HIV consensus guideline recommends antiretroviral treatment regardless of CD4 count, new regimens and possible regimen change for chronic low level viraemia

Commentary on: Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA 2012;308(4):387–402.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Recommendations for...

Antiretroviral Treatment of Adult HIV Infection 2012 Recommendations of the International Antiviral Society–USA Panel

Antiretroviral Treatment of Adult HIV Infection 2012 Recommendations of the International Antiviral Society–USA Panel

Treatment of Adult HIV Infection: Antiretroviral Update and Overview

Up-to-date guidelines for nurse practitioners are critically important to keep up with the continuous advances in HIV treatment. With a key understanding of viral replication, combination therapy, treatment failure, and drug toxicities, the provider is able to have these reference tools to assist in monitoring the infection. Research development continues with a focus on new classes to inhibit different parts of the HIV cycle and drug class resistance and to determine the first- and second-line antiretroviral therapy. The purpose of this article is to provide an overview of the highly active antiretroviral therapy, basic understanding of when to initiate therapy, how to manage patients receiving these medications, treatment regimens, and useful guidelines.

Current HIV Treatment Guidelines - An Overview

Use of highly active antiretroviral therapy has resulted in significant reductions in HIV-related morbidity and mortality. Current therapeutic approaches target cellular entry, viral transcription, and maturation of newly formed virus. Combination therapy is necessary to provide durable suppression of viral replication and immune reconstitution. A variety of consensus treatment guidelines addressing prophylaxis and treatment of HIV infection and opportunistic infections have been developed to serve as resources for clinicians. A summary of U.S. Department of Health and Human Services Guidelines for Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents and International AIDS Society-USA Panel recommendations for Treatment of Adult HIV infection are presented. Considerations for selection of antiretroviral therapy in special populations (e.g., pregnancy, coinfection with tuberculosis, hepatitis B and C virus) are highlighted. U.S. Public Health Service guidelines for management of occupational exposure to HIV and initiation of postexposure prophylaxis are discussed as well as World Health Organization recommendations for use of antiretroviral therapy in resource-limited settings. The pathophysiology of HIV infection, viral load testing methods, viral dynamics, and classification of antiretrovirals are also briefly reviewed.