Genotypic testing is preferable to phenotypic testing because of lower cost, faster turnaround time, and greater sensitivity for detecting mixtures of wild-type and resistant virus.Phenotypic studies are not define for IC 50 concentrationsIf ART is deferred, testing should still be performed because of the greater likelihood that transmitted resistance-associated mutations will be detected earlier in the course of HIV infection. Results of resistance testing may be important when treatment is initiated. Repeat testing at the time ART is initiated should be considered because the patient may have acquired a drug-resistant virus (i.e., superinfection).
Abchsr 5-8% with in 6 weeksof starting.Sensitivity 100% and specificity 50%
Transmission rate of hiv 2 from mother to child 0-4%
only wild-type virus appears to be transmitted to infants by mothers who have mixed populations of wild-type virus and virus with low-level zidovudine resistancedrug-resistance mutations may diminish viral fitness and possibly decrease transmissibilityreduction in maternal HIV viral load but also on pre- and post-expo sure prophylaxis in the infantzidovudine is metabolized to the active triphosphate within the placenta, which may provide additional protection against transmissionZidovudine penetrates the central nervous system (CNS)
Didanosine (ddI) should not be given with ribavirin because of the potential for drug-drug interactions leading to life-threatening ddI-associated mitochondrial toxicity including hepatomegaly/steatosis, pancreatitis, and lactic acidosis .o Zidovudine (ZDV) combined with ribavirin should be avoided when possible because the higher rates of anemia associated with the combination make ribavirin dose reduction necessary .o Abacavir (ABC) has been associated with decreased response to peginterferon plus ribavirin in some
A small subset of ARV-untreated HIV-infected persons (~3%−5%) are able to maintain normal CD4 cell counts for many years (long-term nonprogressors), while an even smaller subset (~1%) are able to maintain suppressed viral loads for years (elite controllers)
Rifabutin s/e uveitis and neutropenia
COTRIMOXAZOLE TREATMENT REDUCED INCIDENCE OF MALARIA.
EFZ .1- >1% RISK OF NTD.IN GENERAL POPULATION .1%TDF 1 - 4% NEPHROTOXICITIES. .5 – 2 % FANCONI
8-40 % OF INDIVIDUALS WHO PRESENT WITH EVIDENCE OF IMMUNOLOGICAL FAILURE BUT VIROLOGICAL SUPPRESSION AND RISK BEING UNNECESSARY SHIFT TO 2ND LINE ART.
Skin rash (10%) – DRV has a sulfonamide moiety; Stevens- Johnson syndrome and erythremamultiformeEtravirine and raltegravir are not approved for use in individuals less than 16 years of age.
Patients receiving A ZT-containing regimens and with low body weight and/or low CD4 cell counts are at greater risk of anaemia. These patients should have routine Hb monitoring 1 month after initiating A ZT and then at least every 3 months. A ZT should not be given if Hb is <7 g/dl.
OUTLINEGuidelines for antiretroviral drugs in Adult and adolescent Pregnancy Post exposure prophylaxis
STRENGTH OF RECOMMENDATION QUALITY OF EVIDENCEA. Strong recommendation I: One or more randomized trials with clinical outcomes and/or validated laboratory endpointsB. Moderate recommendation for the II: One or more well-designed,statement nonrandomized trials or observational cohort studies with long-term clinical outcomesC. Optional recommendation for the III: Expert opinionstatement
Laboratory Monitoring Schedule Prior and After Initiation of Antiretroviral Therapy 2–8 weeks Follow- up ART Entry post-ART Every 3–6 Every 6 Ever Treatment Clinicaly before ART initiation or into initiation or months months y 12 failure indicated modification1 care modification mon √ every 3–6 √ √ clinically stable patients ths √ √ CD4 count months with suppressed viral load, CD4 count can be monitored √ every 3–6 months √ √2 √3 every √ √ Viral load 6–12 months √ √4 √ √ Resistance test √ HLA- if considering B*5701 ABC √ √ √ Tropism testing if considering a if considering a testing CCR5 CCR5 antagonist antagonist or for failure of CCR5 antagonist- Hepatitis B √ √ based regimen √ may repeat if serology negative baseline Basic √ every 6–12 √ √ √ √ months chemistry AST,ALT √ every 6–12 √ √ √ √ months ,BIL √ every 3–6 √ √ √ √ CBC months if on ZDV √ if normal, √ √ √ √ √ Fasting annually consider 4–8 if abnormal if lipid weeks after at last normal starting new measurement at last profile ART measure √ if normal, √ √ √ ment √ Fasting annually if abnormal if normal at glucose at last measurement last measuremen √ √ t √ √ √ Urinalysis7 if on TDF8 Pregnancy test √ √ if starting EFV
HIV drug-resistance testing• HIV drug-resistance testing when they enter into careregardless of initiation of ART (AIII). If therapy is deferred,repeat testing at the time of ART initiation should beconsidered (CIII).• Genotypic testing is recommended as the preferredresistance testing (AIII).• HIV drug-resistance testing should be performed whenchanging ARV regimens in persons with virologic failureand HIV RNA levels >1,000 copies/mL (AI). In persons withHIV RNA levels >500 but <1,000 copies/mL, testing may beunsuccessful but should still be considered (BII).
HIV drug-resistance testing•Drug-resistance testing in the setting of virologic failureshould be performed while the person is taking prescribedARV drugs or, if not possible, within 4 weeks afterdiscontinuing therapy (AII).• Addition of phenotypic to genotypic testing is generallypreferred for persons with known or suspected complexdrug-resistance mutation patterns, particularly to proteaseinhibitors (PIs) (BIII).• Genotypic resistance testing is recommended for allpregnant women prior to initiation of therapy (AIII) and forthose entering pregnancy with detectable HIV RNA levelswhile on therapy (AI).
HLA-B*5701 SCREENING• The Panel recommends screening for HLA-B*5701 beforestarting patients on an abacavir (ABC)-containing regimento reduce the risk of hypersensitivity reaction (HSR) (AI).• The positive status should be recorded as an ABC allergyin the patient’s medical record (AII).• When HLA-B*5701 screening is not readily available, itremains reasonable to initiate ABC with appropriateclinical counseling and monitoring for any signs of HSR(CIII).
CORECEPTOR TROPISM ASSAYS• Coreceptor tropism assay should be performedwhenever the use of a CCR5 inhibitor is beingconsidered (AI).
GOALS FOR ANTIRETROVIRAL THERAPY (ART)•Reduce HIV-associated morbidity and prolong theduration and quality of survival,•Restore and preserve immunologic function,•Maximally and durably suppress plasma HIV viralload and•Prevent HIV transmission.
Initiating Antiretroviral Therapy in Treatment- Naive Patients• All patients with a history of an AIDS-defining illness orwith a CD4 count of <350 cells/mm3 (AI).•ART is also recommended for patients with CD4 countsbetween 350 and 500 cells/mm3 (A/B-II).•ART should also be initiated, regardless of CD4 count, inpatients with the following conditions: HIVAN (AII) and HBVcoinfection when treatment of HBV is indicated (AIII).•A combination ARV drug regimen is also recommended forpregnant women who do not meet criteria for treatmentwith 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 onclinical 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 column A should be combined with the drugs listed in column B A B RemarkNNRTI NRT s I • EFV/TDF/FTC co-formulated • EFV TDF/FTC• LPV/r (twice daily) ZDV/3TC preferred for pregnant womenRitonavir-boosted PI• ATV/r • ATV/r: 300/100 mg qd TDF/FTC• DRV/r • DRV/r: 800/100 mg qdITI • RAL TDF/FTC • RAL: 400 mg bid
• Alternative Regimens (Regimens that are effective and tolerable but have potential disadvantages)A drug from column A should be combined with the drugs listed in columnB A B Remark NNRTI NRTI s• EFV ABC/3TC • ABC/3TC co-formulatedRPV (rilpivirine) TDF/FTC or ABC/3TC • TDF/FTC co-formulatedRitonavir-boosted PI• ATV/r ABC/3TC • ATV/r: 300/100 mg qd• DRV/r • DRV/r: 800/100 mg qd• LPV/r or FPV/r ABC/3TC or TDF/FTC • LPV/r: 400/100 mg bid or 800/200 mg qdITI ABC/3TC • RAL: 400 mg bid• RAL
A drug from column A should be combined with the drugs listed in columnB A BNNRTI NRTIEFV ZDV/3TC (CI) Acceptable NVP TDF/FTC or ZDV/3TC (CI) Regimens (CI)NVP 90 ABC/3TC (CIII) (C1) (Regimens that mayRPV ZDV/3TC (CIII)Ritonavir-boosted PI be selected for some ATV/r CI ZDV/3TC patients but are less DRV/r CIIILPV/r or FPV/r ZDV/3TC (CI) satisfactory and Regimens that mayCCR5 ANTAGONIST be acceptable butMVC ZDV/3TC (CI) or more definitive data TDF/3TC or ABC/3TC (CIII) are needed)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 historyand past and current resistance test results should be usedto identify at least two (preferably three) fully activeagents to combine with an optimized background ARVregimen (AI).• In general, adding a single, fully active ARV in a newregimen is not recommended because of the risk of rapiddevelopment of resistance (BII).
Treatment Experienced Patient• In patients with a high likelihood of clinical progressionand limited drug options, adding a single drug may reducethe risk of immediate clinical progression (CI).• For some highly ART-experienced patients, maximalvirologic suppression is not possible. In this case, ARTshould be continued (AI) with regimens designed tominimize toxicity, preserve CD4 cell counts, and avoidclinical progression.• Discontinuing or briefly interrupting therapy strategy isnot 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 andfor those with seroconversion within last 6 months (CIII).• All pregnant women with acute or recent HIV infectionshould start a combination antiretroviral (ARV)regimen(AI).• If the decision is made to initiate therapy in a person withacute HIV infection, genotypic resistance testing atbaseline will be helpful (AIII). If therapy is deferred,genotypic resistance testing should still be performed(AIII).•Ritonavir (RTV)-boosted PI-based regimen should be usedif therapy is initiated before drug-resistance test results are
HIV-INFECTED WOMEN• ART drugs having interactions with oral contraceptives should usean additional or alternative contraceptive method (AIII). e.g. E and N additional contraceptive method recommended,withATZ/r min 35 mcg of ethinyl estradiol is necessary,with other ritonavirboosted PI ‘s an additional or alternative contraceptive methodrecommended.• Prevention of mother-to-child transmission (PMTCT).• Genotypic resistance testing is recommended for all HIV-infectedpersons, including pregnant women, prior to initiation of ART (AIII)and for women entering pregnancy with detectable HIV RNA levelswhile on therapy (AI).• Efavirenz (EFV) should be avoided in a pregnant woman during thefirst 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 back- bone 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 thedrugs at the same time.
CLINICAL SCENARIO RECOMMENDATIONSHIV-infected Women:pregnant women • Perform HIV ARV drug-resistance and repeat after initiation of therapy if viralwho are ARV naive suppression is suboptimal.and do not require • Prescribe combination ARV drug prophylaxis (i.e., at least 3 drugs) to preventtreatment for their perinatal transmission.own health • Delayed initiation of prophylaxis until after the first trimester of pregnancy can be consid- ered 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 con- tinuous 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 Women:pregnant women • Obtain full ARV drug history, including prior resistance testing, and evaluatewho are ARV need for ARTexperi- enced but for maternal health.not currently re- • Test for HIV ARV drug resistance before reinitiating ARV drugs & retest afterceiving ARV drugs 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: Give zidovudine as continuous infusion during labor.women who have Infants: prophylaxis with a combination ARV drug regimen started as close toreceived no ART the time of birth as possible. Zidovudine given for 6 weeks combined with 3before labor doses of nevirapine in the first week of life ( at birth, 48 hours later,& 96 hours after second ).Infants born to HIV- Prophylaxis with a combination ARV drug regimen started as close to theinfected women time of birth.who have receivedno ART before orduring labor
Concordant and Serodiscordant Couples•For serodiscordant couples who want to conceive, expert consultation isrecommended (AIII).•Partners should be screened and treated for genital tract infectionsbefore 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 intrauterineinsemination, 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 isrecommended (AII).•HBV vaccine should be administered if negativefor hepatitis B (AII).•consultation with an expert in HIV and HBV isrecommended (AIII).•All pregnant women with HIV/HBV coinfectionshould receive a combination ARV drug regimenwith two drugs active against both HIV and HBV(AII). Tenofovir plus lamivudine or emtricitabine isthe 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 contraindicatedduring pregnancy (AIII).•Recommendations for ARV drug use during pregnancy are the samefor women who have chronic HCV as for those without HIV/HCVcoinfection (BIII).•Decisions of mode of delivery should be based on standardobstetric and HIV-related indications alone (BIII).•Infants born to women with HIV/HCV coinfection should beevaluated for HCV infection with anti-HCV antibody testing after age18 months (AII). Infants with a positive anti-HCV antibody shouldundergo confirmatory HCV RNA testing. If earlier diagnosis isindicated or desired, HCV RNA virologic testing between ages 3 and6 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 ofTDF + FTC or TDF + 3TC backbone of a fullysuppressive antiretroviral (ARV) regimen (AI).•If TDF cannot safely be used, the alternativerecommended HBV therapy is entecavir in additionto 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 TBshould be treated with ART (AI).• For patients with CD4 count <200 cells/mm3, ARTshould be initiated within 2–4 weeks of starting TBtreatment (AI).• For patients with CD4 count 200–500 cells/mm3,the Panel recommends initiation of ART within 2–4weeks, or at least by 8 weeks after commencementof TB therapy (AIII).
MYCOBACTERIUM TUBERCULOSIS DISEASE WITH HIV COINFECTION• For patients with CD4 count >500 cells/mm3,most Panel members also recommend starting ARTwithin 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 orwithout ritonavir boosting) is not recommended(AII).
IMPROVING ADHERANCE Strategies to Improve Adherence to Antiretroviral Therapy Strategies Examples multidisciplinary approach accessible, • Nurses, social workers, pharmacists, and medication managerstrusting health care team Establish readiness to start ART Counseling sessions Identify potential barriers to adherence • Psychosocial issues • Active substance abuse or at high risk of relapse prior to starting ART • 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) • For each option, review potential side effects, dosing frequency, pill regimen selection 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 • Adverse effects from medications Assess and simplify regimen, if possible • Complexity of regimen (pill burden, dosing frequency) • Difficulty swallowing large pills• Forgetfulness • Failure to understand dosing instructions
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 disinfectantsolution that will not irritate the skin. WHO recommendsthe use of a chlorhexidine gluconate solution. If running water is not available, clean the site with a gel orother 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 orother 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 antiretroviraltherapy in the community is less than 15%; and• source person has never used antiretroviral therapy;or• source person is unlikely to have HIV infection resistantto antiretroviral therapy , based on antiretroviral therapyand adherence history.Preferred regimens Alternative regimenszidovudine + lamivudine tenofovir + lamivudine
Criteria for treatment with two NRTI + bPI•source person is HIV positive, taking antiretroviral therapyand is known to have signs of, personal history of or provenantiretroviral therapy resistance; or•source person’s HIV status is unknown;the background prevalence of resistance to antiretroviraltherapy in the community exceeds 15%.
Categories of exposurecategory Definition and exampleMild mucous membrane/non-intact skin with smallexposure 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 needlesModerate mucous membrane/non intact skin with largeexposure volumes Or percutaneous superficial exposure with solid needle E.g. : cut or needle stick injury penetrating glovessevere percutaneous with large volume e.g. :needle (>18 G)exposure with visibly blood;deep wound (haemorrhagic wound or very painful) ;volume of blood;previously used intravenously or intra-arterially line .
HIV transmission risk : different routesBlood transfusion 90–95% •Perinatal HIV transmission risk of 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- 0.09%nasaltears, sweat, saliva, urine and faeces Noninfectious unless contaminatedexposure with visible bloodNeedle-stick exposure HBV is 9–30% & for HCV is 1–10%
HIV POST-EXPOSURE PROPHYLAXIS EVALUATIONEXPOSURE HIV+ & HIV+ & HIV STATUS UNKNOWN ASYMPTOMATIC CLINICALLY SYMPTOMATIC MILD CONSIDER 2-DRUG START 2- DRUG USUALLY NO PEP OR CONSIDER 2-DRUG PEP MODERAT START 2-DRUG START 3-DRUG USUALLY NO PEP OR CONSIDER 2-DRUG PEP E SEVERE START 3-DRUG START 3-DRUG USUALLY NO PEP OR CONSIDER 2-DRUG PEP pep regimens to be prescribed by health centers preferred alternative2-drug regimen 1st choice: 2nd choice:(basic pep regimen) Zidovudine (AZT) + Lamivudine Stavudine (d4T) + Lamivudine (3TC) (3TC)3-drug regimen (expanded regimen) -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. >5000• 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.
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-trimoxazole prophylaxis recommendationsCommencing Cd4 not available Cd4 availableprimary CpT WHO clinical Any WHO clinical stage and Cd 4 <200 cells/mm3 or stage Any WHO clinical stage, Cd 4 <350 cells/mm3 and if 3 or 4 (This patient is symptomatic or includes all WHO stage 3 or 4 irrespective of CD4 countTiming the initiation patients with Start co-trimoxazole prophylaxis first.of co-trimoxazole in TB) ART about two weeks later if the patient can tolerate co-trimoxazole Startrelation to initiating and has no symptoms of allergy (rash, hepatotoxicity)ARTpatients allergic Dapsone 100 mg per day, if availableto sulpha-basedmedicationsMonitoring No specific laboratory monitoring is required in patents receiving co-
Recommended schedule for starting and stopping oI prophylaxisopportunisti primary prophylaxis drug of choice discontinue primary discontinuec infection indicated when Cd4 prophylaxis when secondary is Cd4 is prophylaxis when Cd4 isPCP < 200 TMP-SMX 1 DS od >200Toxoplasmosis < 100 TMP-SMX 1 DS od >200CMV retinitis Not indicated Secondary: oral Not applicable >100 ganciclovirCryptococs Not indicated Secondary: Not applicable >100meningitis fluconazoleOral & oesophageal Not indicated Not applicable Not applicable Not indicatedcandidiasis• Co-trimoxazole desensitization Desensitization can be attempted two weeks after a non-severe co-trimoxazole reaction. successful and safe in approximately 70% cases.
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 ofevidence)
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)
WHO PERINATAL GUIDELINESMaternal AZT + infant ARV prophylaxis Maternal triple ARV prophylaxis(Option A) (Option B)Mother Mother Antepartum twice-daily AZT starting at 14 ARV prophylaxis starting 14 weeks of weeks of gestation. At onset of labour, sd-NVP gestation and continued until delivery, or, if and initiation of twice daily AZT + 3TC for 7 breastfeeding, continued until 1 week after days postpartum. all infant exposure to breast milk has If maternal AZT was provided for >4 weeks ended. AZT + 3TC +LPV/rantenatally, omit sd-NVP and AZT + 3TC + ABC AZT + 3TC tail ; in this case, continue maternal AZT during labour and stop at AZT + 3TC + EFV delivery). TDF + 3TC (or FTC) + EFVInfant InfantFor breastfeeding infants:Daily NVP from birth Irrespective of mode of infant feedingfor min of 4 to 6 weeks, and until 1 week after Daily NVP or twice daily AZT from birthall exposure to breast milk has ended. until 4 to 6 weeks of age.Infants receiving replacement feeding only:Daily NVP or sd-NVP + twice-daily AZT frombirth 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 healthSdNVP (+/- antepartum A ZT ) Initiate a non-NNRTI regimenwith no A ZT/3TC tail in last 12 PI preferred over 3 NRTImonthssdNVP (+/- antepartum A ZT ) Initiate an NNRTI regimenwith an A ZT/3TC tail in last 12 If possible, check viral load at 6months months and if >5000 copies/ml, switch to second- line ART with PIsdNVP (+/- antepartum A ZT ) with or Initiate an NNRTI regimenwithout an A ZT/3TC tail over 12 months If possible, check viral load at 6ago months and if >5000 copies/ml, switch to second- line ART with PIOption A Initiate an NNRTI regimenAntepartum A ZT (from as early as 14 If possible, check viral load at 6weeks of gestation) months and if >5000 copies/ml,sdNVP at onset of labour* switch to second- line ART with PIA ZT + 3TC during labour and If no sdNVP was given, start standard NNRTI (viral load does notdelivery* A ZT + 3TC tail for 7 days need to be checked unless clinicallypostpartum* indicated as no sdNVP received)* sd-NVP and A ZT + 3TC can beAll triple ARV regimens (including Option Initiate standard NNRTI regimenomitted if mother receives >4 weeks ofB), irrespective of duration of exposure If EFV-based triple ARV was used forA ZTand time since exposure prophylaxis and no tail (A ZT + 3TC; orantepartumOption B TDF+ 3TC; or TDF + FTC) was givenTriple ARV from 14 weeks gestation when triple ARV was discontinueduntil after all exposure to breast milk after cessation of breastfeeding (orhas ended A ZT + 3TC + LPV/r delivery if formula feeding), checkA ZT + 3TC + ABC viral load at 6 months and if >5000A ZT + 3TC + EFV copies/ml, switch to second-line ARTTDF + [3TC or FTC] + EFV with PI.
WHO clinical staging of HIV disease in adults and adolescents Clinical stage 1 Asymptomatic Persistent generalized lymphadenopathy Clinical stage 2Moderate unexplained weight loss (<10% of measured body wt)Recurrent RTI (sinusitis,tonsillitis,otitis media, pharyngitis)Herpes zosterAngular cheilitisRecurrent oralulceratioPapular pruriticeruptioSeborrhoeicdermatitisFungal nailinfections 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 10 9 /l) and/or chronic thrombocytopenia (below 50 x 10 9 /l)
Clinical stage 4HIV wasting syndromepcp pneumoniaRecurrent severe bacterialpneumoniaChronic herpes simplex infection (orolabial, genital or anorectal of morethan 1 month’s duration or visceral at any site)Oesophageal candidiasis ( trachea, bronchi or lungs)Extrapulmonary tuberculosisKaposi sarcomaCytomegalovirus disease (retinitis or infection of other organs, excludingliver, spleen and lymph nodes)Central nervous system toxoplasmosisHIV encephalopathyExtrapulmonary cryptococcosisDisseminated nontuberculousmycobacteria infectionProgressive multifocalleukoencephalopathyChronic cryptosporidiosisChronic isosporiasisDisseminated mycosis (histoplasmosis,coccidiomycosis)Recurrent septicaemia (including nontyphoidalSalmonella)Lymphoma (cerebral or B cell non-Hodgkin)Invasive cervical carcinomaAtypical disseminated leishmaniasisSymptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy