03.02 management of patients on antiretroviral drugs initiat

Module 3: Management of Patients on Antiretroviral Therapy Unit 2: Initiation and Monitoring of ARV Treatment

Objectives Explain the principles of successful antiretroviral therapy (ART) Explain ART combinations that are used and the rationale for use of national standardized ART regimens Explain drug and non-drug related considerations prior to initiating ART Explain when ART should be initiated and who should be started on ART Describe type of monitoring employed in ART

Principles of Antiretroviral Treatment (ART) ART is part of the comprehensive care of HIV infection Currently ART does not cure HIV infection; it halts viral replication preventing further disease progression Treatment should be planned and started in good time Regular follow up and monitoring is essential Adherence is key to successful treatment Treatment should be stopped/changed when necessary The choice of drugs should take into account Efficacy, tolerability, dosing schedule, affordability and availability

Goals of ART Improved quality of life/increased longevity Reduction of HIV related morbidity and mortality Restoration and preservation of immune function Maximal suppression of HIV replication

1. Suppression of HIV Replication Viral load is a measure of viral replication It is the most important indicator of therapeutic response ARV drugs should be taken in an effective combination to achieve maximal and durable suppression of HIV replication Usually 3 drugs from 2 different classes Suppression of HIV replication results in Stopping/slowing disease progression Delaying the emergence of drug resistance

2. Immune Reconstitution Because ART reduces viral replication it further prevents CD4 cell destruction by HIV Allows CD4 cells to recover both in number and in improved function (evident as control of chronic OIs or KS) As CD4 cells are central to the immune system There is improved overall function of the immune system It takes time for this to become evident clinically in terms of reduced OIs and improved health

3. Clinical Benefits and Improved Quality of Life ART has been associated with a marked reduction in morbidity and mortality associated with HIV infection Decreased hospitalizations Decreased risk of illnesses Reduction in all OIs and malignancies Reduction in AIDS diagnosis and AIDS related deaths Ability to return to work, live a longer more productive life

Keys to Achieving Goals of ART Provider knowledge and experience Understanding of guidelines and best practice Experience in HIV care Rational use of drugs Continuous professional development Patient education, assessment and preparation prior to treatment initiation and continued support while on treatment

Patient Preparation Issue of lifelong continuous treatment Expected benefits Potential side effects of treatment and what to do Necessity for regular follow up Adherence and relation to outcome, drug resistance Adjusting to changes in lifestyle Recreational drug use Use of concomitant medication Medication not to be shared Point of contact if needed

Take-home Messages about ART Not an emergency treatment Benefits take 6 to 8 weeks to become evident Generally should not be initiated in in-patients Treat opportunistic infections first OIs cause >90% of morbidity in HIV Most of the OIs affecting patients are simple to treat ART is only one part of HIV Care All who require ART should first be on Cotrimoxazole Optimize nutrition

Take-home Messages about ART Adherence counseling essential Patients should be prepared and be able to understand Need for strict adherence and relation to outcome Benefits of treatment Life-long commitment to treatment, regular follow-up The Kenyan National Treatment Guidelines should be followed

Antiretroviral Drugs: Best Practice Minimum combination of three drugs from at least 2 different classes drugs 2 NRTIs + NNRTI 2 NRTIs + 2 PIs* (ritonavir boosted PI) 2 NRTIs + PI Never use mono- or dual- therapy Do not adequately suppress viral replication Allow resistance to develop rapidly may adversely affect use of class of drugs involved Triple nucleoside therapy Best avoided as several triple nucleoside regimens have been shown to be inferior to standard 2-class regimens unless essential

Rationale Behind Standardized ARV Drug Therapy Need for a public health approach to ART Affordable, accessible, effective treatment for the majority of patients Success of TB treatment program Simplicity of prescribing Preservation of certain ARV drugs on a population level Simple sequencing of 1 st to 2 nd line Increased efficiency in drug procurement Cost and availability of FDCs

Standard 1 st Line Regimen for Adults and Adolescents Lamivudine + Stavudine + Nevirapine Lamivudine + Stavudine + Efavirenz or

Standard 2 nd Line Regimen for Adults and Adolescents AZT OR Abacavir + Didanosine + Lopinavir/Ritonavir AZT OR Abacavir + Didanosine + Nelfinavir or

For Patients on Non-standard 1 st line Regimens… 1 st Line D4T+ddI+NNRTI AZT+3TC+PI AZT+3TC+ABC 2 nd Line AZT OR ABC+3TC+LPV/r NNRTI + ABC + ddI NNRTI OR LPV/r+ TDF+ d4T

A Note On Fixed Dose Combinations (FDCs) Approved FDCs are available for: Advantages Decreased pill burden Increased adherence Mono or dual therapy not possible (can’t split drug) Lower cost Simplify stock control and forecasting TDF/FTC (Tenofovir/Emtricitabine) ABC/3TC ABC/AZT/3TC d4T/3TC/NVP d4T/3TC AZT/3TC Chosen by GOK for national scale up of ART

Considerations prior to starting ART Logistics Availability of ARVs Sustainability Drug related Drug Interactions Co-infections Contraception Combined toxicity Patient factors Body weight 60kg key in determining dose of Stavudine and Didanosine Kids Patient factors Previous ART use by patient Pregnancy Not a contraindication for ART Effects of ARVs on pregnant woman and fetus- largely unknown Delay starting ARVs until 2 nd trimester Avoid Efavirenz during 1 st trimester (and in women of child bearing potential)

When to Start: Early Initiation of Antiretroviral Therapy Benefits Control of viral replication and mutation Preservation of immune system Decreased risk of selection of resistant virus Possible decreased risk of viral transmission Risks Drug-related reduction in quality of life Greater cumulative drug-related adverse events Possible earlier development of drug resistance Limitation of future treatment options

When to Start: Delayed Initiation of Antiretroviral Therapy Benefits Avoid negative effects on QOL and drug-related adverse events Delay development of drug resistance Preserve future treatment options Risks Possible risk of irreversible immune system destruction Possible greater difficulty in suppressing viral replication Greater likelihood of adverse events Co-infections and drug interactions Immune reconstitution Possible increased risk of HIV transmission

When to Start ART in Adults and Adolescents Where CD4 Testing Unavailable WHO III & IV regardless of total Lymphocyte count WHO II when total lymphocyte count <1200/mm3

When to Start ART in Adults and Adolescents Where CD4 testing available WHO I& II when CD4 < 200/mm 3 WHO stage III when CD4 count < 350/mm 3 WHO stage IV irrespective of CD4 level

Guidance on Clinical Criteria In symptomatic patients with stage 3 and 4 disease CD4 count is not essential for initiating treatment Treatment should not be delayed in these patients where a CD4 test is unavailable CD4 count is however useful and should be carried out where possible Some patients may be asymptomatic but still be severely immunocompromized

Pregnancy and ART Pregnancy is not a contraindication to ART In general, best to defer initiation of ART to after the first trimester (after organogenesis) Efavirenz is contraindicated in pregnancy and should not be prescribed for women with child bearing potential (unless effective contraception is also used- IUD, BTL) Avoid d4T and DDI together; increased risk of lactic acidosis ART greatly decreases vertical transmission and should be offered to all HIV+ pregnant mothers who need treatment

TB/HIV Co-infected Patients Always give TB treatment priority All patients should be on cotrimoxazole prophylaxis Optimum time to start ART in TB/HIV co-infected patients is not known Consider the risk of HIV progression if ART is delayed Balance against risk of having to discontinue therapies because of toxicities, side effects, paradoxical reactions or unforeseen drug/drug interactions if ART is started

ART and TB ART is recommended for all patients with TB with CD4 counts < 200/mm 3 and should be considered in patients with CD4 counts < 350/mm 3 In the absence of CD4 counts, ART is recommended for all patients with TB

ART and TB: When to start Start anti-TB treatment Consider clinical status: start ART as appropriate CD4 count not available Start anti-TB treatment Start ART after completion of TB treatment CD4 count 200-350/mm 3 Start anti-TB treatment Start ART after intensive phase CD4 count 100-200/mm 3 Start anti-TB treatment Start ART as soon as possible CD4 <100/mm 3 Treatment Recommendation CD4 Count

Monitoring Antiretroviral Therapy

Monitoring ART Why? Assess efficacy of intervention Detect other treatable conditions Assessment for drug related toxicities How? Clinical history and examination Laboratory markers

Clinical Monitoring Regular clinical evaluation is important to Assess efficacy of ART Monitor toxicity. Frequency of visits for clinical monitoring First visit at 2 weeks after initiating therapy Ensure that medicines are being taken and stored correctly Note and address possible side effects Assess adherence In stable patients Subsequent visits should be monthly 6-12 months following initiation of ART, clinical appointments may be spaced at 2 to 3 month intervals in compliant and clinically stable patients with an excellent understanding of ART

Clinical Monitoring Plot the patient’s weight and note the trend Falling weight may indicate treatment failure/new illness e.g. TB Determine the patient’s physical condition. Address ongoing medical problems including possibility of failure of treatment through the development of new OIs. Treat inter-current infections Check drug dosages and adjust according to weight. The patients should be given medicines to last for 1 month even when the clinic appointments are less frequent. Adherence should be assessed and appropriate counseling provided at each visit.

Clinical Monitoring: Indicators of Treatment Success Look for: Patient self assessment of well being Decrease or disappearance of symptoms Increase in body weight Decrease in frequency and severity of OIs

Laboratory Monitoring of ART Laboratory tests are recommended for Assessing response to and efficacy of treatment. Monitoring toxicity

Laboratory Monitoring of ART Assessing efficacy of treatment For effective monitoring of efficacy of treatment, CD4 counts, and viral load are essential. Resistance testing where available is a useful adjunct to choice of antiretroviral treatment.

Laboratory Monitoring of ART: CD4 Count Where possible CD4 count should be determined at baseline and thereafter at 6 monthly intervals CD4 count should not be measured during a concurrent infection Delay until > 2 weeks after recovery For consistency CD4 measurements in a patient should be carried out In the same laboratory and preferably at the same time of day.

Laboratory Monitoring of ART: Viral Load Viral load measurements are the most timely and sensitive way of assessing treatment response Where available viral loads should be done routinely at baseline and then 6-monthly Viral load should also be done if possible, when treatment failure is suspected CD4 count response less than expected or falling Where adherence is judged to be poor

Lab Tests: Monitoring For Toxicity Tests for monitoring toxicity Where available the following tests should be done at baseline to enable monitoring ARV drug toxicity Complete blood count (CBC) ALT/SGPT Creatinine Pregnancy test for all women of child bearing potential Fasting lipid profile and glucose, if Protease inhibitors are to be used Serum amylase

Lab tests: Follow up Follow-up laboratory tests: ALT after 1-2 months of treatment when NNRTIs are used. If normal, repeat at 3 months, 6 months and thereafter 6-monthly interval or earlier if clinically indicated. CBC after 1-2 months if Zidovudine is used for treatment. If normal, repeat at 3 months, 6 months and thereafter 6-monthly intervals Fasting lipids annually, if a patient is on protease inhibitors. Evaluation for pregnancy for women of child-bearing potential and pregnancy tests done when indicated. The clinical picture should always be taken into account when monitoring for toxicity

Summary Schedule of Laboratory Monitoring X X 1 X (if on TDF) X X 6m X X X Fasting lipids & glucose (PIs) X X X X (if on NVP) X (if on NVP) X ALT(LFT) X 1 X 1 X 1 X 1 X 1 X Pregnancy test X (if on TDF X (if on TDF) X (if on TDF X (if on TDF) X (if on TDF) X Serum Creatinine X X X X (if on AZT) X (if on AZT) X CBC + Differential X X X X CD4 24m 18m 12m 3m 1-2 months Baseline Test

03.02 management of patients on antiretroviral drugs initiat

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