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ANTIRETROVIRAL THERAPY GUIDELINES

2011

OUTLINE

Guidelines for antiretroviral drugs in Adult and adolescent Pregnancy Post exposure prophylaxis

STRENGTH OF RECOMMENDATION

QUALITY OF EVIDENCE

A. Strong recommendation I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints

B. Moderate recommendation for the statement

II: One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes

C. Optional recommendation for the statement

III: Expert opinion

Laboratory Monitoring Schedule Prior and After Initiation of Antiretroviral Therapy

Entry into care

F o llo w - up b efo re A R T

A R T initiation or

m o d if ica t io n 1

2–8 weeks post-ART

initiation or modification

Every 3–6

months

Every 6 months

Every 12 months

Treatment

failure Clinicaly indicated

CD4 count √ every 3–6 months

√ √ clinically stable patients w ith suppressed viral load, C D 4 count can be monitored e v e ry

6–12 months

√ √

Viral load √ every 3–6 months √ √ 2 √ 3 √ √

Resistance test

√ √ 4 √ √

HLA-B*5701 testing

√ if co n sid er in g ABC

Tropism testing

√ if considering a CCR5 antagonist

√ if considering a CCR5 antagonist or for failure of CCR5 antagonist- based regimen

√

Hepatitis B serology

√ √ may repeat if negative baseline

√

Basic chemistry

√ every 6–12 months

√ √ √ √

A S T ,A L T,B I L


√ √ √ √

CBC


√ √ if on ZDV

√ √

Fasting lipid profile

√ if normal, annually

√ √ consider 4–8 weeks after starting new ART

√ if abnormal at last measurement

√ if normal at last measurement

√

Fasting glucose

√ if normal, annually

√ √ if abnormal at last measurement

√ if normal at last measurement

√

Urinalysis7 √ √ √ if on T D F 8

√ √

Pregnancy test √ if starting E F V √

HIV drug-resistance testing

• HIV drug-resistance testing when they enter into care regardless of initiation of ART (AIII). If therapy is deferred, repeat testing at the time of ART initiation should be considered (CIII).• Genotypic testing is recommended as the preferred resistance testing (AIII).• HIV drug-resistance testing should be performed when changing ARV regimens in persons with virologic failure and HIV RNA levels >1,000 copies/mL (AI). In persons with HIV RNA levels >500 but <1,000 copies/mL, testing may be unsuccessful but should still be considered (BII).

HIV drug-resistance testing •Drug-resistance testing in the setting of virologic failure should be performed while the person is taking prescribed ARV drugs or, if not possible, within 4 weeks after discontinuing therapy (AII).• Addition of phenotypic to genotypic testing is generally preferred for persons with known or suspected complex drug-resistance mutation patterns, particularly to protease inhibitors (PIs) (BIII).• Genotypic resistance testing is recommended for all pregnant women prior to initiation of therapy (AIII) and for those entering pregnancy with detectable HIV RNA levels while on therapy (AI).

HLA-B*5701 SCREENING

• The Panel recommends screening for HLA-B*5701 before starting patients on an abacavir (ABC)-containing regimen to reduce the risk of hypersensitivity reaction (HSR) (AI).• The positive status should be recorded as an ABC allergy in the patient’s medical record (AII).• When HLA-B*5701 screening is not readily available, it remains reasonable to initiate ABC with appropriate clinical counseling and monitoring for any signs of HSR (CIII).

CORECEPTOR TROPISM ASSAYS

• Coreceptor tropism assay should be performed whenever the use of a CCR5 inhibitor is being considered (AI).

GOALS FOR

ANTIRETROVIRAL THERAPY (ART)

•Reduce HIV-associated morbidity and prolong the duration and quality of survival,•Restore and preserve immunologic function,•Maximally and durably suppress plasma HIV viral load and•Prevent HIV transmission.

Initiating Antiretroviral Therapy in Treatment- Naive Patients

• All patients with a history of an AIDS-defining illness or with a CD4 count of <350 cells/mm3 (AI).•ART is also recommended for patients with CD4 counts between 350 and 500 cells/mm3 (A/B-II).•ART should also be initiated, regardless of CD4 count, in patients with the following conditions: HIVAN (AII) and HBV coinfection when treatment of HBV is indicated (AIII).•A combination ARV drug regimen is also recommended for pregnant women who do not meet criteria for treatment with the goal to prevent perinatal transmission (AI).•Patients may choose to postpone therapy, and providers, on a case-by-case basis, may elect to defer therapy based on clinical and/or psychosocial factors.

What to Start Preferred Regimens (Regimens with optimal and durable

efficacy, favorable tolerability and toxicity profile, and ease of use)

A drug from co lum n A shou ld be com b in ed w ith the drugs lis ted in co lum n B

A B Remarks NNRTI N R T

I • EFV /TD F/FTC co-formulated

• E FV

TDF/FTC

• LPV/r (twice daily) ZDV/3TC preferred for pregnant women Ritonavir-boosted PI

TDF/FTC

• ATV /r: 300 /100 mg qd • D R V /r: 800/10 0 mg qd

• ATV /r • D R V /r ITI

TDF/FTC

• R AL: 400 mg bid • RAL

• Alternative Regimens (Regimens that are effective and

tolerable but have potential disadvantages) A drug from co lum n A shou ld be com b ined w ith the drugs lis ted in co lum n B

A B Remark

s NNRTI N R T I • ABC /3TC co-formulated

• EFV ABC/3TC RPV (rilpivirine) TDF/FTC or ABC/3TC • TD F/FTC co-formulated

Ritonavir-boosted PI

ABC/3TC

• AT V /r: 300 /100 mg qd • D R V /r: 800/100 mg qd

• ATV /r • D R V /r • LPV/r or FPV/r ABC/3TC or TDF/FTC • LPV/r: 400/100 mg bid or 800/200 mg

qd ITI

ABC/3TC • RAL: 400 mg bid • RAL

Acceptable Regimens (CI) (Regimens that may be selected for some patients

but are less satisfactory and Regimens that

may be acceptable but more definitive

data are needed)

A drug from co lum n A shou ld be com b ined w ith the drugs lis ted in co lum nB

A B NNRTI N R T I EFV ZD V/3TC (CI)

NVP TDF/FTC or ZDV/3TC (CI) 90 (C1)

NVP ABC/3TC (CIII) RPV ZDV/3TC (CIII) Ritonavir-boosted PI

ZD V/3TC

ATV /r C I D R V /r C III

LPV/r or FPV/r ZDV/3TC (CI)

CCR5 ANTAGONIST

MVC ZDV/3TC (CI) or

TDF/3TC or ABC/3TC (CIII) ITI

ZDV/3TC (CIII) RAL

Treatment Experienced Patient

• Expert advice is critical and should be sought.• Drug-resistance testing should be obtained.• To design a new regimen, the patient’s treatment history and past and current resistance test results should be used to identify at least two (preferably three) fully active agents to combine with an optimized background ARV regimen (AI). • In general, adding a single, fully active ARV in a new regimen is not recommended because of the risk of rapid development of resistance (BII).

Treatment Experienced Patient

• In patients with a high likelihood of clinical progression and limited drug options, adding a single drug may reduce the risk of immediate clinical progression (CI). • For some highly ART-experienced patients, maximal virologic suppression is not possible. In this case, ART should be continued (AI) with regimens designed to minimize toxicity, preserve CD4 cell counts, and avoid clinical progression.• Discontinuing or briefly interrupting therapy strategy is not recommended (AI).

ACUTE HIV INFECTION • Diagnosis • Clinical suspicion• Negative or reactive EIA with negative or

indeterminate Western blot should be followed by a HIV RNA levels

• Confirmatory HIV antibody test should be performed over the next 3 months.

RECOMMENDATIONS• Treatment should be considered optional at this time and for those with seroconversion within last 6 months (CIII). • All pregnant women with acute or recent HIV infection should start a combination antiretroviral (ARV)regimen (AI).• If the decision is made to initiate therapy in a person with acute HIV infection, genotypic resistance testing at baseline will be helpful (AIII). If therapy is deferred, genotypic resistance testing should still be performed (AIII).•Ritonavir (RTV)-boosted PI-based regimen should be used if therapy is initiated before drug-resistance test results are available (AIII).

HIV-INFECTED WOMEN • ART drugs having interactions with oral contraceptives should use an additional or alternative contraceptive method (AIII). e.g. E and N additional contraceptive method recommended,with ATZ/r min 35 mcg of ethinyl estradiol is necessary,with other ritonavir boosted PI ‘s an additional or alternative contraceptive method recommended.• Prevention of mother-to-child transmission (PMTCT).• Genotypic resistance testing is recommended for all HIV-infected persons, including pregnant women, prior to initiation of ART (AIII) and for women entering pregnancy with detectable HIV RNA levels while on therapy (AI).• Efavirenz (EFV) should be avoided in a pregnant woman during the first trimester (AIII).

Perinatal guidelines• Combined antepartum, intrapartum, and

infant ARV prophylaxis is recommended to prevent perinatal transmission (AI).

• Antepartum ART – Start as soon as possible for own health After first trimester if not for own health (AI)

• Adding single-dose intrapartum/newborn nevirapine to the standard ARV regimens is not recommended(AI).

• If an ARV drug regimen is stopped acutely for severe toxicity, severe pregnancy-induced hyperemesis , all ARV drugs should be stopped and reinitiated at the same time (AIII).

Perinatal guidelines• When HIV is diagnosed late in pregnancy, ARV should be

initiated pending results of resistance testing (BIII).• Breastfeeding is not recommended for HIV infected

women including those receiving ART(AII).• Regarding continuation of the ARV regimen for therapeutic

indications after delivery are the same as for non pregnant individuals.(AIII) (promise trial underway).

• Discontinuation postnatal, Ideally all drugs should be stopped simultaneously. If NNRTI based regimens, 1) continue the dual-NRTI backbone for 7 days. 2) If efavirenz-based NNRTI continue other ARV agents for up to 30 days 3) alternatively replace the NNRTI with PI then to discontinue all the drugs at the same time.

CLINICAL SCENARIO RECOMMENDATIONS HIV-infected pregnant women who are ARV naive and do not require treatment for their own health

Women: • Perform HIV ARV drug-resistance and repeat after initiation of therapy if viral suppression is suboptimal. • Prescribe combination ARV drug prophylaxis (i.e., at least 3 drugs) to prevent perinatal transmission. • Delayed initiation of prophylaxis until after the first trimester of pregnancy can be considered in women who are receiving ARV drugs solely for prevention of perinatal transmission, but earlier initiation of prophylaxis may be more effective in reducing perinatal transmission of HIV. •Avoid use of efavirenz or other potentially teratogenic drugs in the first trimester. •use one or more NRTIs with good transplacental passage as a component of the ARV regimen. • Continue ARV prophylaxis regimen during the intrapartum period (zidovudine given as continuous infusiona during labor while other ARV agents are continued orally). • Schedule cesarean delivery at 38 weeks of gestation if plasma HIV RNA remains >1,000 copies/mL near the time of delivery. Infants: • Start zidovudine as soon as possible after birth and administer for 6 weeks

HIV-infected pregnant women who are ARV experienced but not currently receiving ARV drugs

Women: • Obtain full ARV drug history, including prior resistance testing, and evaluate need for ART for maternal health. • Test for HIV ARV drug resistance before reinitiating ARV drugs & retest after initiating combination ARV regimen if viral suppression is suboptimal. Infants: • Start zidovudine as soon as possible after birth and administer for 6 weeks.b

HIV-infected women who have received no ART before labor

Women: Give zidovudine as continuous infusion during labor. Infants: prophylaxis with a combination ARV drug regimen started as close to the time of birth as possible. Zidovudine given for 6 weeks combined with 3 doses of nevirapine in the first week of life ( at birth, 48 hours later,& 96 hours after second ).

Infants born to HIV-infected women who have received no ART before or during labor

Prophylaxis with a combination ARV drug regimen started as close to the time of birth.

Concordant and Serodiscordant Couples

•For serodiscordant couples who want to conceive, expert consultation is recommended (AIII). •Partners should be screened and treated for genital tract infections before attempting to conceive (AII).•HIV-infected female with an HIV-uninfected male partner, - artificial insemination (AIII).•For HIV-infected men with an HIV-uninfected female partner, donor sperm from an HIV-uninfected male for insemination the use of sperm preparation techniques coupled with either intrauterine insemination, in vitro fertilization, or intracytoplasmic sperm injection (AII). •In a serodiscordant couple who wishes to conceive, Initiation of ART for the HIV-infected partner is recommended if the infected partner has a CD4 count ≤550 cells/mm3 (AI). with CD4 counts >550 cells/mm3, initiation of ART could be

considered (BIII).

HIV/HBV Coinfection in pregnancy

•Screening for hepatitis B virus (HBV) infection is recommended (AII). •HBV vaccine should be administered if negative for hepatitis B (AII).•consultation with an expert in HIV and HBV is recommended (AIII). •All pregnant women with HIV/HBV coinfection should receive a combination ARV drug regimen with two drugs active against both HIV and HBV (AII). Tenofovir plus lamivudine or emtricitabine is the preferred (AI).

HIV/HBV Coinfection in pregnancy

• If ARV drugs are discontinued postpartum , frequent monitoring of liver function tests for exacerbation of HBV infection is recommended, with prompt reinitiation of treatment for both HIV and HBV if a flare is suspected (BIII).

• liver transaminases should be assessed 1 month following initiation of ARV drugs and at least every 3 months thereafter (BIII).

• Within 12 hours of birth, infants born to women with HBV infection should receive

hepatitis B immune globulin (HBIG) first dose of the HBV vaccine series (AI).

HIV/HCV Coinfection in Pregnancy

•Screening for hepatitis C virus infection is recommended (AIII).•Interferon alfa not recommended and ribavirin is contraindicated during pregnancy (AIII).•Recommendations for ARV drug use during pregnancy are the same for women who have chronic HCV as for those without HIV/HCV coinfection (BIII).•Decisions of mode of delivery should be based on standard obstetric and HIV-related indications alone (BIII).•Infants born to women with HIV/HCV coinfection should be evaluated for HCV infection with anti-HCV antibody testing after age 18 months (AII). Infants with a positive anti-HCV antibody should undergo confirmatory HCV RNA testing. If earlier diagnosis is indicated or desired, HCV RNA virologic testing between ages 3 and 6 months can be performed (AIII).

HIV-2 Infection and Pregnancy

• A regimen with TWO NRTIS AND A BOOSTED PI currently is recommended because they have SIGNIFICANT CLINICAL DISEASE OR CD4 COUNTS <500 CELLS/MM3 (AIII).

• Based on available data on safety in pregnancy,ZDV+3TC+LPV/r would be preferred (AIII).TDF+3TC/FTC+LPV/r can be considered as an alternative (BIII).

• Optimal PROPHYLACTIC regimens have not been defined following approaches:

• A boosted PI-based regimen (two NRTIs plus lopinavir/ritonavir) for prophylaxis, with the drugs stopped postpartum(BIII); OR Zidovudine prophylaxis alone during pregnancy and intrapartum (BIII).

• NNRTIs AND ENFUVIRTIDE are not active against HIV-2 (AIII).

• Infants should receive 6-WK AZT prophylactic regimen (BIII).

Monitoring in Pregnancy• CD4 count should be monitored at the initial

visit (AI) and at least every 3 monthly (BIII).Monitoring of CD4 count may be performed every 6 months in patients on ART for more than2–3 years & have sustained viral suppression (BIII)

• Plasma HIV RNA levels should be monitored at the initial visit (AI); 2–4 weeks after initiating (or changing) antiretroviral (ARV) drug regimens (BI); monthly until RNA levels are undetectable (BIII); and then at least every 3 months (BIII). HIV RNA levels also should be assessed at approximately 34–36 weeks’ gestation to inform decisions about mode of delivery (AIII).

Management of Antiretroviral Drug Resistance during Pregnancy

• Women who have documented zidovudine resistance and are on regimens that do not include zidovudine for their own health should still receive intravenous zidovudine during labor whenever possible, along with their established antiretro viral (ARV) regimens (AII).

• In women who are receiving a stavudine-containing regimen, the drug should be discontinued during labor while intra venous zidovudine is being administered (AII).

HBV/HIV COINFECTION

•ART should be initiated with the combination of TDF + FTC or TDF + 3TC backbone of a fully suppressive antiretroviral (ARV) regimen (AI).•If TDF cannot safely be used, the alternative recommended HBV therapy is entecavir in addition to a fully suppressive ARV regimen (BI).

HBV/HIV COINFECTION • Entecavir has activity against HIV; its use

for HBV treatment without ART in patients with dual infection may result in the selection of the M184V mutation that confers HIV resistance to 3TC and FTC (AII).

• If ART needs to be modified due to HIV virologic failure and the patient has adequate HBV suppression, the ARV drugs active against HBV should be continued for HBV treatment in combination with other suitable ARV agents to achieve HIV suppression (AIII).

HCV/HIV COINFECTION • ART should be started in HCV/HIV-coinfected

persons in accordance with the Panel’s recommendation for initiating ART in ART-naïve patients.

• Patients receiving or considering therapy with ribavirin should avoid ddI, d4T, and ZDV.

• Patients should be monitored by following alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at 1 month and then every 3 months after initiation of ART.

MYCOBACTERIUM TUBERCULOSIS DISEASE WITH HIV COINFECTION• All HIV-infected patients with diagnosed active TB should be treated with ART (AI).• For patients with CD4 count <200 cells/mm3, ART should be initiated within 2–4 weeks of starting TB treatment (AI).• For patients with CD4 count 200–500 cells/mm3, the Panel recommends initiation of ART within 2–4 weeks, or at least by 8 weeks after commencement of TB therapy (AIII).

MYCOBACTERIUM TUBERCULOSIS DISEASE WITH HIV COINFECTION

• For patients with CD4 count >500 cells/mm3, most Panel members also recommend starting ART within 8 weeks of TB therapy (BIII).• If a protease inhibitor (PI)-based regimen is used, rifabutin is the preferred rifamycin (AII). • Coadministration of rifampin and PIs (with or without ritonavir boosting) is not recommended (AII).

IMPROVING ADHERANCEStrategies to Improve Adherence to Antiretroviral Therapy

Strategies Examples

multidisciplinary approach accessible, trusting health care team

• Nurses, social workers, pharmacists, and medication managers

Establish readiness to start ART Counseling sessions

Identify potential barriers to adherence prior to starting ART

• Psychosocial issues • Active substance abuse or at high risk of relapse • Low literacy level • Busy daily schedule and/or travel away from home • Lack of disclosure of HIV diagnosis • Skepticism about ART • Lack of prescription drug coverage

Provide resources for the patient • Referrals for mental health and/or substance abuse treatment • Resources to obtain prescription drug coverage • Pillboxes

Involve the patient in antiretroviral (ARV) regimen selection

• For each option, review potential side effects, dosing frequency, pill burden, storage requirements, food requirements, and consequences of nonadherence

Assess adherence at every clinic visit • Use a simple checklist the patient can complete in the waiting room • Have other members of the health care team also assess

adherance • Ask the patient open-ended questions (e.g., In the last 3 days,

please tell me how you took your medicines.) Identify the type of nonadherence • Failure to fill the prescription(s)

• Failure to take the right dose(s) at the right time(s) • Nonadherence to food requirements

Identify reasons for nonadherence Assess and simplify regimen, if possible

• Adverse effects from medications • Complexity of regimen (pill burden, dosing frequency) • Difficulty swallowing large pills• Forgetfulness • Failure to understand dosing instructions • Inadequate understanding of drug resistance and its relationship to

adherence • Pill fatigue • Other potential barriers

Post exposure Prophylaxis

• The first dose of PEP should be administered within the first 72 hours of exposure and the risk evaluated as soon as possible.

• Special leave from work should be considered for a period of time eg. 2 weeks (initially) then, as required based on assessment of the exposed person’s mental state, side effects and requirements.

PEP is not indicated • if the exposed person is HIV-positive from a

previous exposure;• in chronic exposure;• if the exposure does not pose a risk of

transmission, that is, after: exposure of intact skin to potentially infectious body fluids, sexual intercourse using a condom that remains intact

• any exposure to non-infectious body fluids (such as faeces, saliva, urine and sweat)

• if the exposure occurred more than 72 hours previously.

If the skin is broken following an injury with a used needle or sharp instrument, the following is recommended.

Do not squeeze or rub the injury site. Wash the site immediately using soap or a mild disinfectant solution that will not irritate the skin. WHO recommends the use of a chlorhexidine gluconate solution. If running water is not available, clean the site with a gel or other hand-cleaning solution Do not use strong solutions, such as bleach or iodine,

After a splash contacts unbroken skin, do the following.

Wash the area immediately.If running water is not available, clean the area with a gel or other hand- rub solution, whatever is customarily available.Do not use strong disinfectants.

After a splash contacts the eye, do the following• Irrigate the exposed eye immediately with water or

normal saline.• Sit in a chair, tilt the head back and have a colleague

gently pour water or normal saline over the eye, pulling the eyelids up and down to make sure the eye is cleaned thoroughly.

• If contact lenses are worn, leave these in place while irrigating the eye, as they form a barrier over the eye and will help protect it. Once the eye has been cleaned, remove the contact lenses and clean them in the normal manner. This will make them safe to wear again.

After a splash contacts the mouth, do the following

• Spit the fluid out immediately.• Rinse the mouth thoroughly, using water or saline, and

spit again. Repeat this process several times..

Criteria for treatment

with two NRTI inhibitors• HIV status of the source person is unknown; and • background prevalence of resistance to antiretroviral therapy in the community is less than 15%; and• source person has never used antiretroviral therapy;or• source person is unlikely to have HIV infection resistant to antiretroviral therapy , based on antiretroviral therapy and adherence history.Preferred regimens Alternative regimens

zidovudine + lamivudine tenofovir + lamivudine stavudine + lamivudine

Criteria for treatment with two NRTI + bPI

•source person is HIV positive, taking antiretroviral therapy and is known to have signs of, personal history of or proven antiretroviral therapy resistance; or•source person’s HIV status is unknown;the background prevalence of resistance to antiretroviral therapy in the community exceeds 15%.

Categories of exposurecategory Definition and exampleMild exposure

mucous membrane/non-intact skin with small volumes E.g. : a superficial wound (erosion of the epidermis) with a plain or low calibre needle, or contact with the eyes or mucous membranes, subcutaneous injections following small-bore needles

Moderate exposure

mucous membrane/non intact skin with large volumes Or percutaneous superficial exposure with solid needleE.g. : cut or needle stick injury penetrating gloves

severe exposure

percutaneous with large volume e.g. :needle (>18 G) with visibly blood;deep wound (haemorrhagic wound or very painful) ;volume of blood;previously used intravenously or intra-arterially line .

HIV transmission risk : different routes

•HIV transmission risk of

Blood transfusion 90–95%

Perinatal 20–40%Sexual intercourse 0.1 to 10% Vaginal 0.05–0.1% Anal 0.065–0.5% Oral 0.005–0.01% Injecting drugs use 0.67%Needle stick exposure 0.3% Mucous membrane splash to eye, oro-nasal

0.09%

tears, sweat, saliva, urine and faeces exposure

Noninfectious unless contaminated with visible blood

Needle-stick exposure HBV is 9–30% & for HCV is 1–10%

HIV POST-EXPOSURE PROPHYLAXIS EVALUATION EXPOSURE HIV+ &

ASYMPTOMATIC HIV+ & CLINICALLY SYMPTOMATIC

HIV STATUS UNKNOWN

MILD CONSIDER 2-DRUG START 2- DRUG USUALLY NO PEP OR CONSIDER 2-DRUG PEP MODERATE

START 2-DRUG START 3-DRUG USUALLY NO PEP OR CONSIDER 2-DRUG PEP SEVERE START 3-DRUG START 3-DRUG USUALLY NO PEP OR CONSIDER 2-DRUG PEP

pep regim ens to be prescribed by health centers preferred alternative 2-drug regimen (basic pep regimen)

1st choice: Zidovudine (AZT ) + Lam ivudine (3TC)

2nd choice: Stavudine (d4T ) + Lam ivudine (3TC)

3-drug regim en (expanded regim en) -consult expert for starting 3rd drug eg LPV/r, NLF or IND

NACO: WHAT IS DIFFERENT?• Plasma viral load: A baseline PVL is not

necessary. With optimum adherence and a potent regimen, undetectable levels should be achieved at 6 months after ART initiation.

• All patients should undergo at least two counselling sessions before the initiation of ART.

• TDF + 3TC + (NVP or EFV): if toxicity or other contraindications to AZT or d4T.

• ‘triple NRTI approach’ will not be used in the National programme until further data is available globally

Intolerance to both ZDV and d4T : in this case, TDF+3TC as fixed dose combination will be provided, after consultation with the SACEP. Drug supply mechanism to be decided.

Intolerance to both NVP and EFV: in this case, ATV/r as a substitution ARV will be provided upon review and approved by the SACEP. The patient shall be managed and provided ATV/r by the COE for at least 6 months and then transferred back to the referring ART center.

FAILURE• Clinical, immunological and virological definitions of

treatment failure for first-line regimen.

• Certain WHO clinical stage 3 conditions like pulmonary TB , severe bacterial infections indicate treatment failure and second line ART considered.

• Some stage 4 conditions TB lymph nodes & plueral, recurrent bacteria pneumonia , oesophageal candidiasis may not indicate Rx failure and 2nd line should not be cosidered.

>5000

Procedure for second line ART Counsel patient & Reinforce adherence to 1st line ART while waiting for SACEP(State AIDS Clinical Expert Panel) review. Send all patient informationto SACEP/COE by courier.

• Refer to SACEP for appointment dates by email - inform patient of date and to attend in person.

• All patient who require 2nd line ART will be reviewd by SACEP irrespective of from where they took 1st line.

• SACEP will document its decision ie Provide 2nd line ART, Not eligible for 2nd line ART, Re-evaluate• Patient should undergo minimum of 3

counseling sessions for treatment readiness.• The NACO second line regimen (TDF + 3TC

+ ATV/R)

Co-trim oxazole prophylaxis recom m endations Com mencing primary CpT

Cd4 not available Cd4 available W HO clinical stage 3 or 4 (This includes all patients with TB)

Any W HO clinical stage and Cd 4 <200 cells/mm 3 or Any W HO clinical stage, Cd 4 <350 cells/m m 3 and if patient is symptomatic or W HO stage 3 or 4 irrespective of CD4 count

Timing the initiation of co-trimoxazole in relation to initiating ART

Start co-trim oxazole prophylaxis first. Start ART about two weeks later if the patient can tolerate co-trimoxazole and has no sym ptom s of allergy (rash, hepatotoxicity)

patients allergic to sulpha-based medications

Dapsone 100 mg per day, if available

Monitoring No specific laboratory monitoring is required in patents receiving co-trimoxazole

• Co-trimoxazole desensitization Desensitization can be attempted two weeks after a non-severe co-trimoxazole reaction. successful and safe in approximately 70% cases.

Recommended schedule for starting and stopping oI prophylaxis opportunistic infection

primary prophylaxis indicated when Cd4

is

drug of choice discontinue primary prophylaxis when

Cd4 is

discontinue secondary

prophylaxis when Cd4 is

PCP < 200 TMP-SMX 1 DS od >200 Toxoplasmosis < 100 TMP-SMX 1 DS od >200 CMV retinitis Not indicated Secondary: oral

ganciclovir Not applicable >100

Cryptococs meningitis

Not indicated Secondary: fluconazole

Not applicable >100

Oral & oesophageal candidiasis

Not indicated Not applicable Not applicable Not indicated

WHO : WHATS DIFFERENT ?• It is recommended to treat all patients with WHO

clinical stage 3 and 4 irrespective of CD4 count.(Strong recommendation, low quality of evidence)

• Start one of the following regimens in ART-naive individuals eligible for treatment.

• AZT + 3TC + EFV

• AZT + 3TC + NVP

• TDF + 3TC (or FTC) + EFV

• TDF + 3TC (or FTC) + NVP(Strong recommendation, moderate quality of evidence)

Triple nucleoside regimens AZT + 3TC + ABC or A ZT + 3TC + TDF should be used for individuals who are unable to tolerate or have contraindications to NNRTI- based regimens, particularly in the following situations:• HIV/ TB coinfection;• pregnant women;• chronic viral hepatitis B;• HIV-2 infection.(Conditional recommendation, low quality of evidence)

WHEN TO SWITCH THERAPY?

• Where available, use viral load ( VL) to confirm treatment failure.(Strong recommendation, low quality of evidence)

• Where routinely available, use VL every 6 months to detect viral replication.

(Conditional recommendation, low quality of evidence)• A persistent VL of >5000 copies/ml

confirms treatment failure.(Conditional recommendation, low quality of evidence)

THIRD-LINE REGIMENS• Include new drugs likely to have anti-

HIV activity, such as integrase inhibitors and second-generation NNRTIs and PIs.(Conditional recommendation, low quality of evidence)

• Patients on a failing second-line regimen with no new ARV options should continue with a tolerated regimen.(Conditional recommendation, very low quality of evidence)

Monitoring ART in those at higher risk of adverse events

ARV drug

Major tox ic ity High-risk situation s

d4T

Lipodystrophy Neuropathy Lactic acidosis

Age >4 0 years

CD4 count of <20 0 cells/mm3

BMI >25 (Wt >75kg)

A ZT

Anaemia

Neutropenia CD4 count of <20 0 cells/mm3

BMI <18.5 (or wt <50 kg)

TDF

R en al dysfunction

U nderly ing renal disease

Age >4 0 years, BMI <18.5 (or body weight <5 0 kg) Diabetes mellitus, Hypertension

Concomitant use of a bPI or nephrotoxic drugs

NVP

Hepatotoxicity

H C V and H B V coinfection

WHO PERINATAL GUIDELINESMaternal AZT + infant ARV prophylaxis Maternal triple ARV prophylaxis (Option A) (Option B) Mother Mother Antepartum twice-daily AZT starting at 14 weeks of gestation. At onset of labour, sd-NVP and initiation of twice daily AZT + 3TC for 7 days postpartum.

If maternal AZT was provided for >4 weeks antenatally, omit sd-NVP and AZT + 3TC tail ; in this case, continue maternal AZT during labour and stop at delivery).

ARV prophylaxis starting 14 weeks of gestation and continued until delivery, or, if breastfeeding, continued until 1 week after all infant exposure to breast milk has ended. AZT + 3TC +LPV/r AZT + 3TC + ABC AZT + 3TC + EFV TDF + 3TC (or FTC) + EFV

Infant Infant For breastfeeding infants:Daily NVP from birth for min of 4 to 6 weeks, and until 1 week after all exposure to breast milk has ended. Infants receiving replacement feeding only: Daily NVP or sd-NVP + twice-daily AZT from birth until 4 to 6 weeks of age.

Irrespective of mode of infant feeding Daily NVP or twice daily AZT from birth until 4 to 6 weeks of age.

Previous ARV exposure for PMTCT Recommendations for initiation of ART when needed for treatment of HIV for maternal health

SdNVP (+/- antepartum A ZT ) with no A ZT/3TC tail in last 12 months

Initiate a non-NNRTI regimen

PI preferred over 3 NRTI sdNVP (+/- antepartum A ZT ) with an A ZT/3TC tail in last 12 months

Initiate an NNRTI regimen

If possible, check viral load at 6 months and if >5000 copies/ml, switch to second- line ART with PI

sdNVP (+/- antepartum A ZT ) with or without an A ZT/3TC tail over 12 months ago



Option A

Antepartum A ZT (from as early as 14 weeks of gestation)

sdNVP at onset of labour*

A ZT + 3TC during labour and

delivery* A ZT + 3TC tail for 7 days

postpartum*

* sd-NVP and A ZT + 3TC can be omitted if mother receives >4 weeks of A ZT antepartum



If no sdNVP was given, start standard NNRTI (viral load does not need to be checked unless clinically indicated as no sdNVP received)

All triple ARV regimens (including Option B), irrespective of duration of exposure and time since exposure

Option B

Triple ARV from 14 weeks gestation until after all exposure to breast milk has ended A ZT + 3TC + LPV/r A ZT + 3TC + ABC A ZT + 3TC + EFV TDF + [3TC or FTC] + EFV

Initiate standard NNRTI regimen

If EFV-based triple ARV was used for prophylaxis and no tail (A ZT + 3TC; or TDF+ 3TC; or TDF + FTC) was given when triple ARV was discontinued after cessation of breastfeeding (or delivery if formula feeding), check viral load at 6 months and if >5000 copies/ml, switch to second-line ART with PI.

WHO clinical staging of HIV disease in adults and adolescents Clinical stage 1 Asymptomatic Persistent generalized lymphadenopathy Clinical stage 2

Moderate unexplained weight loss (<10% of measured body wt) Recurrent RTI (sinusitis,tonsillitis,otitis media, pharyngitis) Herpes zoster Angular cheilitis Recurrent oral ulceratio Papular pruritic eruptio Seborrhoeic dermatitis Fungal nail infections Clinical stage 3 Unexplained severe weight loss (over 10% of presumed or measured body weight) Unexplained chronic diarrhoea for longer than 1 month Unexplained persistent fever (intermittent or constant for > 1 month) Persistent oral candidiasis Oral hairy leukoplakia Pulmonary tuberculosis Severe bacterial infections (e.g. pneumonia, empyema, meningitis, pyomyositis, bone or joint infection, bacteraemia, severe pelvic inflammatory disease) Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis Unexplained anaemia (below 8 g/dl ), neutropenia (below 0.5 x 109/l) and/or chronic thrombocytopenia (below 50 x 109/l)

Clinical stage 4 HIV wasting syndrome pcp pneumonia Recurrent severe bacterial pneumonia Chronic herpes simplex infection (orolabial, genital or anorectal of more than 1 month’s duration or visceral at any site) Oesophageal candidiasis ( trachea, bronchi or lungs) Extrapulmonary tuberculosis Kaposi sarcoma Cytomegalovirus disease (retinitis or infection of other organs, excluding liver, spleen and lymph nodes) Central nervous system toxoplasmosis HIV encephalopathy Extrapulmonary cryptococcosis Disseminated nontuberculous mycobacteria infection Progressive multifocal leukoencephalopathy Chronic cryptosporidiosis Chronic isosporiasis Disseminated mycosis (histoplasmosis, coccidiomycosis) Recurrent septicaemia (including nontyphoidal Salmonella) Lymphoma (cerebral or B cell non-Hodgkin) Invasive cervical carcinoma Atypical disseminated leishmaniasis Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy

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