Antiretroviral Therapy For HIV Infection Research Articles

Electronic medication monitoring-informed counseling to improve adherence to combination anti-retroviral therapy and virologic treatment outcomes: a meta-analysis.

Adherence to combination anti-retroviral therapy for HIV infection is a primary determinant of treatment success, but is often suboptimal. Previous studies have suggested that electronic medication monitoring-informed counseling is among the most effective adherence intervention components. Our objective was to review available evidence about the effectiveness of monitoring-informed counseling and to aggregate findings into quantitative estimates of the effect of such intervention on medication adherence and virologic treatment outcomes. We searched PubMed for papers reporting on randomized controlled trials comparing intervention groups receiving monitoring-informed counseling as one of the intervention components versus control groups not receiving such counseling for their effect on medication adherence and viral load concentrations. The standardized mean difference (SMD) in adherence and the odds ratio (OR) of undetectable HIV RNA in intervention versus control groups were the common effect sizes. Random-effect models with inverse variance weights were used to aggregate findings into pooled effect estimates with 95% confidence limits (CI). A total of 13 studies were included. Adherence was significantly higher in intervention groups than in control groups (SMD 0.51, 95% CI 0.31-0.71). Patients in intervention groups were significantly more likely to have undetectable HIV RNA concentrations than patients in control groups (OR 1.35, 95% CI 1.12-1.63). However, in studies in which monitoring-informed counseling was the only intervention component, the difference in adherence and virologic response between intervention and control groups was not statistically significant. Electronic monitoring-informed counseling improved adherence and virologic response compared with control groups not receiving such counseling in studies in which it was one out of multiple intervention components, but not in studies where it was the only intervention component.

U2 What do men who have sex with men (MSM) taking post-exposure prophylaxis (PEP) for hiv following sexual exposure report about their recent sexual risk-taking behaviour?

Background/introduction High-risk sexual behaviour plays a significant role in the increasing incidence of HIV infection among men who have sex with men (MSM) in the UK, despite the availability of post-exposure prophylaxis following sexual exposure(PEPSE). Aim(s)/objectives Behavioural interventions to encourage safer sexual practices need to be effective and acceptable for their target population. Therefore, this study aims to identify the attitudes and interpretation of risk of MSM taking PEPSE. Methods Data was collected as part of an ongoing randomised controlled trial evaluating a psychological intervention in reducing risk behaviour amongst MSM prescribed PEPSE. The intervention group received two 30-minute telephone interventions implementing augmented motivational interviewing. In this study, 30 participants were selected from the intervention arm and their interventions analysed for thematic content. Results Themes included: circumstances of event that led to PEPSE; participant’s interpretation of risk; emotions associated with risk; disclosure of HIV status; value attributed to consequences of risk; and reason for seeking PEPSE. Discussion/conclusion Risks were mostly reported in the context of unprotected anal intercourse (UAI) with casual partners, without discussion of HIV status. One theme that arose was the use of mobile-phone applications to seek casual sexual partners. Reasons given for engaging in UAI included anxiety over suggesting condom use, engaging in UAI as a form of “self-harm”, and alcohol intoxication. Concern about the morbidity and stigma associated with HIV and the desire for relationships were motivating factors for avoiding HIV. PEPSE was frequently described as an insight into life-long antiretroviral therapy for HIV infection.

Association of Abnormal Liver Function Parameters with HIV Serostatus and CD4 Count in Antiretroviral-Naive Rwandan Women.

We determined the associations of HIV infection/CD4 count with markers of hepatocellular damage [elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and liver synthetic function (decreased albumin) in HIV-infected (HIV+) antiretroviral therapy (ART)-naive and uninfected (HIV−) Rwandan women. In 2005, 710 HIV+ ART-naive and 226 HIV− women enrolled in the Rwanda Women's Interassociation Study and Assessment. Liver enzymes were measured with abnormality defined as either AST or ALT ≥1.25 times the upper limit of normal. Low serum albumin level was defined as <3.5 g/dl. Multivariable logistic regression analysis identified independent predictors of elevated AST/ALT and low serum albumin. HIV− women had the lowest prevalence (6.6%) of abnormal AST/ALT, with the highest prevalence (16.4%) in HIV+ women with CD4 <200 cells/μl (p=0.01). The odds of having serum albumin <3.5 g/dl was 5.7-fold higher in HIV+ than HIV− women (OR=5.68, 95% CI: 3.32–9.71). The risk of low albumin decreased from low to high CD4 count, with OR=2.62, 95% CI: 1.66, 4.14 and OR=1.57, 95% CI: 1.01, 2.43 in HIV+ women with a CD4 count <200 and 200–350 cells/μl, respectively vs. HIV+ with CD4 >350 (p<0.001 and p<0.05 for all comparisons). Our findings suggest that HIV-associated liver damage may occur in ART-naive patients. Although liver abnormality prevalences in this cohort of HIV-infected Rwandan women are less than reported in developed countries, caution is needed for risk assessment measures to monitor and screen HIV-infected patients pre- and post-ART initiation in African clinical settings to curtail potential risks associated with HIV infection.

A study of the adverse effects of antiretroviral therapy for HIV infection

Abstract Background The introduction of highly active antiretroviral therapy (HAART) has led to significant reduction in acquired immune deficiency syndrome (AIDS)-related morbidity and mortality. Unfortunately, up to 25% of patients discontinue their initial HAART regimen because of treatment failure, toxic effects or noncompliance within the first few months of therapy. Aims To assess adverse effects of antiretroviral therapy and its adherence in HIV infected patients in a resource-restricted setting in India. Methods A group of 400 HIV infected patients, attending class-A ART clinic attached to tertiary care hospital in Mumbai, was studied retrospectively over the period of one year from the initiation of ART to observe and assess adverse effects of ART. Data was obtained from patient treatment record sheet after due permission from ART officer. Results Most common adverse effect was Anemia(17.5%). Baseline CD4 count of less than or equal to 200cells/mm 3 was found to be significantly associated with the incidence of adverse effects ( p value Conclusion As HAART is only option for HIV/AIDS till date; to optimize adherence and thus, efficacy of ART, clinicians must focus on preventing adverse effects whenever possible, promoting the early recognition and reversal of potentially serious adverse effects, and reducing the potential for adverse drug interactions.

A run-in period is needed in randomized controlled trials of directly observed antiretroviral therapy for HIV infection.

A run-in period is needed in randomized controlled trials of directly observed antiretroviral therapy for HIV infection.

A TB-HIV/AIDS coinfection model and optimal control treatment

We propose a population model for TB-HIV/AIDS coinfection transmission dynamics, which considers antiretroviral therapy for HIV infection and treatments for latent and active tuberculosis. The HIV-only and TB-only sub-models are analyzed separately, as well as the TB-HIV/AIDS full model. The respective basic reproduction numbers are computed, equilibria and stability are studied. Optimal control theory is applied to the TB-HIV/AIDS model and optimal treatment strategies for co-infected individuals with HIV and TB are derived. Numerical simulations to the optimal control problem show that non intuitive measures can lead to the reduction of the number of individuals with active TB and AIDS.

Ritonavir-boosted darunavir combined with raltegravir or tenofovir–emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial

Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir-emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962. Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112-133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI -0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively). Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL. European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories.

Loss to clinic and five-year mortality among HIV-infected antiretroviral therapy initiators.

Missing outcome data due to loss to follow-up occurs frequently in clinical cohort studies of HIV-infected patients. Censoring patients when they become lost can produce inaccurate results if the risk of the outcome among the censored patients differs from the risk of the outcome among patients remaining under observation. We examine whether patients who are considered lost to follow up are at increased risk of mortality compared to those who remain under observation. Patients from the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who newly initiated combination antiretroviral therapy between January 1, 1998 and December 31, 2009 and survived for at least one year were included in the study. Mortality information was available for all participants regardless of continued observation in the CNICS. We compare mortality between patients retained in the cohort and those lost-to-clinic, as commonly defined by a 12-month gap in care. Patients who were considered lost-to-clinic had modestly elevated mortality compared to patients who remained under observation after 5 years (risk ratio (RR): 1.2; 95% CI: 0.9, 1.5). Results were similar after redefining loss-to-clinic as 6 months (RR: 1.0; 95% CI: 0.8, 1.3) or 18 months (RR: 1.2; 95% CI: 0.8, 1.6) without a documented clinic visit. The small increase in mortality associated with becoming lost to clinic suggests that these patients were not lost to care, rather they likely transitioned to care at a facility outside the study. The modestly higher mortality among patients who were lost-to-clinic implies that when we necessarily censor these patients in studies of time-varying exposures, we are likely to incur at most a modest selection bias.

Early suppressive antiretroviral therapy in HIV infection is associated with measurable changes in the corpus callosum.

The purpose of this study was to examine the impact of early suppressive antiretroviral therapy (ART) on brain structure and neurocognitive outcomes. We conducted an observational study of subjects within 1 year of HIV infection. Ten ART-naïve and 10 ART-suppressed individuals were matched for age and infection duration and age-matched to 10 HIV-seronegative controls. Quantitative brain imaging and neurocognitive data were analyzed. Subjects on suppressive ART had diminished corpus callosum structural integrity on macromolecular and microstructural imaging, higher cerebrospinal fluid percent, higher depression scores, and lower functional performance. Early suppressive ART may alter the trajectory of neurological progression of HIV infection, particularly in the corpus callosum.

Efficacy of initial antiretroviral therapy for HIV-1 infection in adults: a systematic review and meta-analysis of 114 studies with up to 144 weeks' follow-up.

BackgroundA comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines.MethodsGroup-based, systematic review and meta-analysis of initial antiretroviral therapy studies, in adults, of ≥48 weeks duration, reported through December 31, 2012. Size-weighted, intention-to-treat efficacy was calculated. Parameters of study design/eligibility, participant and treatment characteristics were abstracted. Multivariable, random effects, linear regression models with backwards, stepwise selection were then used to identify variables associated with efficacy.Outcome MeasuresAntiviral efficacy (undetectable plasma viral load) and premature cessation of therapy.Results114 studies were included (216 treatment groups; 40,124 participants; mean CD4 count 248 cells/µL [SD 81]; mean HIV-1 plasma viral load log10 4.9 [SD 0.2]). Mean efficacy across all groups was 60% (SD 16) over a mean 82 weeks' follow-up (SD 38). Efficacy declined over time: 66% (SD 16) at 48 weeks, 60% (SD 16) at 96 weeks, 52% (SD 18) at 144 weeks. The most common reason for treatment cessation was participant decision (11%, SD 6.6). Efficacy was higher with ‘Preferred’ than ‘Alternative’ regimens (as defined by 2013 United States antiretroviral guidelines): 75% vs. 65%, respectively, difference 10%; 95%CI 7.6 to 15.4; p<0.001. In 98 groups (45%) reporting efficacy stratified by pre-treatment viral load (< or ≥100,000 copies/mL), efficacy was greater for the lower stratum (70% vs. 62%, respectively, difference 8.4%; 95%CI 6.0 to 10.9; p<0.001). This difference persisted within ‘Preferred’ regimens. Greatest efficacy was associated with use of tenofovir-emtricitabine (vs. other nucleoside analogue backbones) and integrase strand transfer inhibitors (vs. other third drug classes).ConclusionInitial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy, but are more effective when commenced at plasma viral loads <100,000 copies/mL. Rising viral load should be considered an indication for starting treatment. Integrase inhibitors offer a treatment advantage (vs. other third drug classes).

Tuberculosis Immune Reconstitution Inflammatory Syndrome in children initiating Antiretroviral Therapy for HIV infection: A systematic literature review.

People with HIV initiating combination antiretroviral therapy are at risk for tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). While this syndrome has been well researched in adults, little is known about the incidence, case fatality, underlying immunopathology and treatment approaches in children. Major databases were searched for articles related to TB-IRIS in children. Data were abstracted using standardized forms. Thirteen studies were identified: 6 retrospective and 2 prospective cohort studies, 1 cross-sectional study, 3 case reports and 1 case series. In total, 303 cases of TB-IRIS were described, of which 270 were unmasking TB-IRIS, 12 paradoxical TB-IRIS and 21 were not classifiable due to lack of key information. None of the cohort studies had investigation of TB-IRIS as its primary aim. Nine studies were from Africa, 3 from Asia and 1 from Latin America. Age at cART initiation (reported by 12 studies) ranged from 1 month to 16 years. Median time from start of cART to IRIS diagnosis (reported by 8 studies) ranged from 8 days to 16 weeks. Few deaths attributable to TB-IRIS were recorded. Treatment was only discussed in 2 case studies, both of which reported children receiving corticosteroids. No studies evaluated risk factors for, or immunopathogenesis of, pediatric TB-IRIS. There is a paucity of information available on TB-IRIS in children. Future research assessing incidence, risk factors, case fatality and optimal treatment or prevention strategies of TB-IRIS is needed.

Nonclinical Safety Profile of BMS-986001, a Nucleoside Transcriptase Inhibitor for Combination Retroviral Therapy.

Nucleoside reverse transcriptase inhibitors (NRTIs)/nucleotide reverse transcriptase inhibitors are key components of combination antiretroviral therapy for HIV infection. First-generation NRTIs are associated with mitochondrial toxicity in patients, mainly due to inhibition of human DNA polymerase γ (hDNA polγ) that manifests as adverse events such as lipodystrophy, lactic acidosis, myopathy, cardiomyopathy, or nephropathy in patients. In chronic nonclinical studies in rodents and nonrodents, eukaryotic (host) mitochondrial toxicity manifests as some drug-specific toxicities similar to human toxicity. BMS-986001, a novel thymidine analog with minimal hDNA polγ inhibition, has demonstrated antiretroviral activity in early clinical studies. The primary toxicity of BMS-986001 in rats and monkeys is bone marrow dyserythropoiesis with associated decreases in red blood cell mass. Additionally, at high doses, severe platelet reductions accompanied by cutaneous petechiae began during weeks 8 and 11 in 3 of 60 monkeys in chronic toxicity studies. In a 6-month study, platelet reductions required euthanasia of the 2 affected monkeys (300 mg/kg/d) at week 14, but with dose reduction (200 mg/kg/d) remaining monkeys had no platelet changes. One affected monkey (200 mg/kg/d) in a 9-month study completed dosing and its platelet counts recovered during a 1-month recovery. Formation of platelet-bound immunoglobulin in the presence of BMS-986001, together with rapid and complete platelet recovery in the absence of BMS-986001, suggested that platelet decreases in monkeys may be immune mediated. No findings indicative of mitochondrial toxicity were observed in rats or monkeys given BMS-986001, suggesting an improved safety profile compared to marketed NRTI or tenofovir disoproxil fumarate.

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Therapeutic Drug Monitoring and Pharmacogenetic Study of HIV-Infected Ethnic Chinese Receiving Efavirenz-Containing Antiretroviral Therapy with or without Rifampicin-Based Anti-Tuberculous Therapy

ObjectivesPlasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese.MethodsHIV-infected patients with or without TB who had received combination antiretroviral therapy containing efavirenz (600 mg daily) for two weeks or greater were enrolled for determinations of CYP2B6 G516T polymorphism and plasma efavirenz concentrations with the use of polymerase-chain-reaction restriction fragment-length polymorphism and high-performance liquid chromatography, respectively.ResultsFrom October 2009 to August 2012, 171 HIV-infected patients, including 18 with TB, were enrolled 113 (66.1%) with CYP2B6 G516G, 55 (32.2%) GT, and 3 (1.8%) TT genotype. Patients receiving rifampicin had a significantly lower median plasma efavirenz concentration than the control group (2.16 vs 2.92 mg/L, P = 0.003); however, all patients achieved target plasma concentration (>1 mg/L). Patients with GT or TT genotype had a significantly higher plasma concentration than those with GG genotype (2.50 vs 3.47 mg/L for GT genotype and 8.78 mg/L for TT genotype, P<0.001). Plasma efavirenz concentration >4 mg/L was noted in 38 (22.2%) patients, which was associated with a lower weight (per 10-kg increase, odds ratio, 0.52; 95% confidence interval, 0.33–0.83) and GT or TT genotype (odds ratio, 4.35; 95% confidence interval, 1.97–9.59) in multivariate analysis.ConclusionsDespite combination with rifampicin, sufficient plasma efavirenz concentrations can be achieved in HIV-infected Taiwanese with TB who receive efavirenz 600 mg daily. Carriage of CYP2B6 516 GT and TT genotypes and a lower weight are associated with higher plasma efavirenz concentrations.

Role of IL-6 in Mycobacterium avium–Associated Immune Reconstitution Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is a major adverse event of antiretroviral therapy in HIV infection, and paradoxically occurs as HIV viremia is suppressed and CD4 T cell numbers recover. IRIS reflects pathogenic immune responses against opportunistic infections acquired during the period of immunodeficiency, but little is understood about the mechanisms of inflammatory pathology. In this study, we show that IL-6 and C-reactive protein levels transiently rise at the time of the IRIS event in HIV-infected patients, unmasking Mycobacterium avium complex infection after starting antiretroviral therapy. To directly test the role of IL-6 in IRIS pathology, we used a model of experimentally inducible IRIS in which M. avium-infected T cell-deficient mice undergo a fatal inflammatory disease after reconstitution with CD4 T cells. We find that IL-6 neutralization reduces C-reactive protein levels, alleviates wasting disease, and extends host survival during experimental IRIS. Moreover, we show that combined blockade of IL-6 and IFN-γ further reduces IRIS pathology, even after the onset of wasting disease. The combination of these clinical and experimental-model data show that the IL-6 pathway is not only a biomarker of mycobacterial IRIS but also a major mediator of pathology distinct from IFN-γ and may be a useful target for therapeutic intervention.

Mortality and its predictors among antiretroviral therapy naïve HIV-infected individuals with CD4 cell count ≥350 cells/mm3 compared to the general population: data from a population-based prospective HIV cohort in Uganda

Background Evidence exists that even at high CD4 counts, mortality among HIV-infected antiretroviral therapy (ART) naïve individuals is higher than that in the general population. However, many developing countries still initiate ART at CD4 ≤350 cells/mm3. Objective To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm3 with mortality in the general Ugandan population and to investigate risk factors for death. Design Population-based prospective HIV cohort. Methods The study population consisted of HIV-infected people in rural southwest Uganda. Patients were reviewed at the study clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios were estimated using Poisson regression. Indirect methods were used to calculate standardised mortality ratios (SMRs). Results A total of 374 participants with CD4 ≥350 cells/mm3 were followed for 1,328 person-years (PY) over which 27 deaths occurred. Mortality rates (MRs) (per 1,000 PY) were 20.34 (95% CI: 13.95–29.66) among all participants and 16.43 (10.48–25.75) among participants aged 15–49 years. Mortality was higher in periods during which participants had CD4 350–499 cells/mm3 than during periods of CD4 ≥500 cells/mm3 although the difference was not statistically significant [adjusted rate ratio (aRR)=1.52; 95% CI: 0.71–3.25]. Compared to the general Ugandan population aged 15–49 years, MRs were 123% higher among participants with CD4 ≥500 cells/mm3 (SMR: 223%, 95% CI: 127–393%) and 146% higher among participants with CD4 350–499 cells/mm3 (246%, 117%–516). After adjusting for current age, mortality was associated with increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95% CI: 3.82–27.15) and decreasing body mass index (BMI) (aRR comparing categories ≤17.4 Kg/m2 and ≥18.5 Kg/m2: 6.11, 2.30–16.20). Conclusion HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm3 had a higher mortality than the general population. After adjusting for age, the main predictors of mortality were WHO clinical stage and BMI.

What is Needed for Optimal Therapeutic Drug Monitoring?

BioanalysisVol. 6, No. 2 EditorialWhat is needed for optimal therapeutic drug monitoring?William ClarkeWilliam ClarkeDepartment of Pathology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Sheikh Zayed Tower B-1020F, Baltimore, MD 21287, USA. Search for more papers by this authorEmail the corresponding author at wclarke@jhmi.eduPublished Online:14 Jan 2014https://doi.org/10.4155/bio.13.314AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: harmonizationlaboratory improvementpersonalized medicineproficiency testingquality assurance–QCtherapeutic drug monitoringReferences1 Pippenger CE, Gillen HW. Gas chromatographic analysis for anticonvulsant drugs in biologic fluids. Clin. Chem.15(7),582–590 (1969).Crossref, Medline, CAS, Google Scholar2 Feldman RG, Pippenger CE. The relation of anticonvulsant drug levels to complete seizure control. J. Clin. Pharmacol.16(1),51–59 (1976).Crossref, Medline, CAS, Google Scholar3 Kupferberg HJ. Quantitative estimation of diphenylhydantoin, primidone and phenobarbital in plasma by gas-liquid chromatography. Clin. Chim. Acta29(2),282–288 (1970).Crossref, Medline, CAS, Google Scholar4 Kupferberg HJ, Longacre-Shaw J. Mephobarbital and phenobarbital plasma concentrations in epileptic patients treated with mephobarbital. Ther. Drug Monit.1(1),117–122 (1979).Crossref, Medline, CAS, Google Scholar5 Levy G. What are narrow therapeutic index drugs? Clin. Pharmacol. Ther.63(5),501–505 (1998).Crossref, Medline, CAS, Google Scholar6 Oette M, Kroidl A, Gobels K et al. Predictors of short-term success of antiretroviral therapy in HIV infection. J. Antimicrob. Chemother.58(1),147–153 (2006).Crossref, Medline, CAS, Google Scholar7 Teng JF, Mabasa VH, Ensom, MH. The role of therapeutic drug monitoring of imatinib in patients with chronic myeloid leukemia and metastatic or unresectable gastrointestinal stromal tumors. Ther. Drug Monit.34(1),85–97 (2012).Crossref, Medline, CAS, Google Scholar8 Bach DM, Straseski JA, Clarke W. Therapeutic drug monitoring in cancer chemotherapy. Bioanalysis2(5),863–879 (2010).Link, CAS, Google Scholar9 Horowitz GL. Establishment and use of reference values. In: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics (5th Edition). Burtis CA, Ashwood ER, Bruns, DE (Eds). Elsevier Saunders, St. Louis, MO, USA, 95–118 (2012).Google ScholarFiguresReferencesRelatedDetails Vol. 6, No. 2 Follow us on social media for the latest updates Metrics Downloaded 184 times History Published online 14 January 2014 Published in print January 2014 Information© Future Science LtdKeywordsharmonizationlaboratory improvementpersonalized medicineproficiency testingquality assurance–QCtherapeutic drug monitoringFinancial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Tuberculosis Immune Reconstitution Inflammatory Syndrome in Children Initiating Antiretroviral Therapy for HIV Infection: A Systematic Literature Review

Tuberculosis Immune Reconstitution Inflammatory Syndrome in Children Initiating Antiretroviral Therapy for HIV Infection: A Systematic Literature Review

French 2013 guidelines for antiretroviral therapy of HIV-1 infection in adults.

IntroductionThese guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART) of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure.MethodsTen members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process.ResultsART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine), or a ritonavir-boosted protease inhibitor (atazanavir or darunavir). Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression with or without identified opportunistic infection, and person who injects drugs are addressed. Options for optimization of ART once virologic suppression is achieved are discussed. Evaluation and management of virologic failure are described, the aim of any intervention in such situation being to reduce plasma viral load to <50 copies/ml.ConclusionThese guidelines recommend that any HIV-positive individual should be treated with ART. This recommendation was issued both for the patient’s own sake and for promoting treatment as prevention.

Loss to Clinic and Five-Year Mortality among HIV-Infected Antiretroviral Therapy Initiators

Loss to Clinic and Five-Year Mortality among HIV-Infected Antiretroviral Therapy Initiators