HIV i Base training for advocates Part One Introduction to

HIV i-Base training for advocates Part One: Introduction to HIV Section 7: Drug users and ARVs treatment 3rd Edition: January 2008 HIV i-Base: 3rd Floor East,Thrale Hse, 44-46 Southwark St, London SE11UN. Tel: +44 (0)20 7407 8488 admin@i-Base.org.uk www.i-Base.info www.-Base.nfo HIV i-Base Treatment training for advocates Part One: Section 7 Section 1: The immune system and CD4 count Section 2: Virology, HIV and viral load Section 3: Introduction to ARVs Section 4: Side effects of ARVs Section 5: OIs and co-infections Section 6: HIV and pregnancy Section 7: Drug users and ARVs Section 8: Clinical trials and research Section 9: Learning resources: science support modules Appendices Third edition January 2008 Second edition June 2005 First edition November 2004 Written and edited by: Simon Collins, Polly Clayden, Mauro Guarinieri, Svilen Konov, Roman Dudnik, Ben Cheng and Sipho Mthathi, Matt Williams. HIV i-Base: basc tranng for advocates  January 2008 Contents www.-Base.nfo Treatment training for advocates: January 2008 HIV -Base. http://www.-Base.nfo page Contents Introducton to ths resource Introducton to course outlne Secton 1 - The mmune system and CD4 count 1.1 Introducton 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12 1.13 1.14 1.15 1.16 Ams for Secton 1 Definton of AIDS (SIDA) Basc organs n the body How the mmune system works How HIV specfically nteracts wth mmune system CD4 count as ‘surrogate marker’ How quckly does HIV progress n dfferent people Interpretng CD4 results: CD4 count and CD4 percentage Dfferences between adults and chldren Dfferent stages of nfecton CD4 level cut-offs for opportunstc nfectons Use of CD4 count n gudelnes for startng therapy Glossary: Secton one Questons: Secton 1 Course evaluaton for Secton 1 16  v v 1 Secton 2:Vrology, HIV and vral load 2.1 Introducton 2.2 Ams for Secton 2 2.3 Definton of HIV 2.4 Other causes of llness 2.5 HIV and nfecton 2.6 Vral dynamcs of early and chronc nfecton 2.7 Renfecton wth HIV 2.8 What s a vral load test 2.9 Hstory of vral load technology 2.10 Impact of confectons on vral load 2.11 Compartments and sanctuary stes 2.12 Importance of vral load on-treatment and off-treatment 2.13 Vral lfecycle, drug resstance and adherence 2.14 2.15 2.16 2.17 How CD4 and vral load are related Glossary: Secton 2 Questons: Secton 2 Course evaluaton for Secton 2 HIV i-Base: basc tranng for advocates  January 2008 Contents www.-Base.nfo Secton 3: Introducton to ARVs 3.1 Introducton to Secton 3 3.2 Ams for Secton 3 3.3 What s combnaton therapy? 3.4 Do the drugs really work? 3.5 How HIV drugs work - man types of drugs 3.6 Treatment gudelnes 3.7 When to start treatment 3.8 Why three or more drugs are used 3.9 Reducng vral load to less than 50 copes/mL 3.10 Treatment choce 3.11 Sde effects 3.12 Can I change treatments? 3.13 Can I take a break n my treatment? 3.14 Recreatonal drugs, alcohol and complementary therapy 3.15 Adherence - and why t s so mportant 3.16 Tps to help adherence... 3.17 What f I forget to take my plls? 3.18 Resstance to ARVs 3.19 Treatment falure 3.20 Glossary: Secton 3 3.21 Questons: Secton 3 3.22 Course evaluaton for Secton 3 Secton 4: Sde effects of ARVs 4.1 Introducton 4.2 Ams for secton four 4.3 General questons 4.4 General sde effects 4.5 More serous sde effects assocated wth WHO combnatons 4.6 Other sde effects 4.7 How to report sde effects 4.8 How sde effects are graded 4.9 Sde effects dary 4.10 Glossary: Secton 4 4.11 Questons: Secton 4 4.12 Course evaluaton for Secton 4 27 42 HIV i-Base: basc tranng for advocates  January 2008 Contents www.-Base.nfo Sesson 5: Opportunstc Infectons (OIs) and mportant co-nfectons 5.1 Introducton 5.2 Ams for Sectons 5 5.3 Approach to each OI 5.4 GI nfectons: garda, cryptosporda, mcrosporda 5.5 5.6 5.7 5.8 5.9 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 Candda (canddass) and other skn problems PCP TB MAI and MAC Hepatts B and C CMV Toxoplasmoss Cryptococcal menngts Cancer: lymphoma, and sarcoma Wastng and weght loss Malara Summary table of OIs and effect of ARV treatment Glossary: Secton 5 Questons: Secton 5 Course evaluaton for Secton 5 67 OIs Secton 6: HIV and pregnancy 6.1 Introducton 6.2 Ams for secton 6 6.3 General questons 6.4 Mother’s health and pregnancy 6.5 Prenatal care and treatment 6.6 Safety of HIV drugs n pregnancy 6.7 Sde effects and pregnancy 6.8 Resstance n pregnancy 6.9 Other screenng and tests 6.10 Other nfectons 6.11 Drugs and the baby’s health 6.12 Choces for delvery and use of C-secton 6.13 When the baby s born 6.14 Breastfeedng 6.15 Mother’s health after the baby s born 6.16 Other useful nformaton 6.17 Glossary: Secton 6 6.18 Questons: Secton 5 6.19 Course evaluaton for Secton 6 79 HIV i-Base: basc tranng for advocates v January 2008 Contents www.-Base.nfo Secton 7: Drug users and ARVs 7.1 Introducton 7.2 7.3 7.4 7.5 Ams for Secton 7 General questons Comprehensve and accessble care Interactons between recreatonal drugs and antretrovrals 92 7.6 Why ths theoretcal nformaton s not as useful as controlled nteracton studes n humans 7.7 7.8 7.9 7.10 7.11 Interactons wth other ARVs Interactons wth methadone Table I: Interactons between antretrovrals and rave drugs Questons: Secton 7 Course evaluaton of Secton 7 101 Secton 8: Clncal trals and research 8.1 Introducton 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 8.10 8.11 8.12 8.13 8.14 8.15 Ams for ths secton Why trals are mportant Developng a new treatment: Phase I, II, III and IV studes Hypothess and endponts Three man types of tral desgn Randomsed, double-blnd, placebo-controlled trals Other types of studes Gradng gven to dfferent types of evdence Glossary of terms How studes are reported Patent nvolvement n clncal studes and research Issues of confidentalty for advocates nvolved n research Summary of dfferent advocacy roles Multple choce test questons 8.16 Course evaluaton of Secton 8 Learnng resources: Scence Support modules 9.1 Introducton 9.2 How to read a graph 9.3 9.4 9.5 9.6 What s an average What happens when you take a drug Drug levels, drug actvty and sde effect 122 122 123 125 127 129 Common mathematcal sgns, symbols, statstcal and medcal terms 131 9.7 9.8 Unts of measurement Log value converson table v 132 134 January 2008 HIV i-Base: basc tranng for advocates Contents www.-Base.nfo Appendces Appendx I Appendx II 1993 CDC AIDS survellance case definton WHO classficaton system for HIV nfecton 135 136 137 138 140 141 Appendx III OIs lsted by dsease type Appendx IV Drugs and doses of European lcensed ARVs Appendx V Further readng Appendx VI Answers to questons for each secton HIV i-Base: basc tranng for advocates v January 2008 Introducton www.-Base.nfo Introduction to this resource Ths tranng resource uses eght work unts for the basc course. The format s very smple. Other unts can be added f they are more approprate to dfferent stuatons. Ths resource s part of a copyrght-free project that s avalable on the -Base webste to download n varous formats, or to work onlne. As wth other treatment nformaton produced by -Base we encourage translatons nto other languages. It s wrtten for people who do not have a scentfic background or medcal tranng. For people who already have a basc understandng of the way HIV and treatment works we plan to extend ths modules to produce an ntermedate course. Some of the sessons are very short, and have smple questons. Ths s so that anyone can start learnng about treatment, and n turn pass that nformaton on to others. Even f you are not very academc, and ths tranng s dfficult, you can stll be a very effectve advocate and actvst. Ths tranng wll help you understand the background to traetment ssues. The tranng materal has been wrtten n a way that makes t easer for you to then explan the nformaton agan to other people wthout a medcal background. As communty advocates and traners, t s mportant to understand and explan thngs that people may not be ntally very nterested n. And explan them n a way that makes the new nformaton relevant to gettng better care. Most people don’t want to know about scence - they just want to get on wth ther lves. But you wll need to explan the scence behnd how thngs work. It means gettng people to beleve n thngs that they can’t see, and gettng them to trust n thngs that are too small to see wth ther own eyes. We can’t see a vrus, or a CD4 cell or any of the thngs that are tested n blood wth the naked eye. We can’t see whether one pll or another wll work better or at all. But understandng a bt about how treatment works does empower people to have more control over ther treatment and ther choces. Ths course s wrtten by treatment advocates who have had no formal medcal tranng and who are mostly HIV-postve – and we’ve tred to remember the bggest surprses that we found as we developed our own treatment knowledge. Sometmes t’s the surprses that keep you learnng – because they show how dfferent thng are to how you magned them. Hopefully some of these wll be helpful n developng your own treatment nterest – once you start, you realse there s always more to learn. HIV i-Base: basc tranng for advocates v January 2008 Introducton www.-Base.nfo Introduction to course programme Sections 1-8 – Introduction to HIV The first six sections are to introduce the most important aspects of treatment to an intermediate standard. The am for each secton s to provde a general understandng for each area. Ths wll form the structure for more advanced tranng and your own research n the future. Understandng and completng ths would enable a good grasp of 90% of the ssues nvolved n HIV and treatment. Although ths course presents a structure for what you need to learn about HIV, the approach to learnng wll be more practcal than just readng or takng notes. Advocacy s based on a problem-solvng. Ths nvolves an approach to new nformaton. You wll never reach a pont where you suddenly know everythng. You wll always need to use research to confirm the thngs you thnk that you know, and to find out new thngs that you don’t. Ths s also because nformaton tself changes very quckly. Each secton then has around 15-20 questons that you should be able to answer. The am for the first secton of basc tranng s to get famlar wth the most mportant terms and concepts. You do not need to know everythng about each area n detal, and t wll be too much to deal wth f you try to learn everythng straght away. These first eght sectons are to provde the basc structure to buld on. HIV i-Base: basc tranng for advocates v January 2008 Secton 7: Drug users and ARVs www.-Base.nfo Session 7: Drug users and ARVs “All patients who meet eligibility criteria and want treatment should receive it, including IDUs, sex-business workers and other populations. Access to HIV treatment should not be artificially restricted due to political or social constraints. Specifically there should be no categorical exclusion of injection drug users from any level of care.” WHO’s 2004 Protocols for HIV/AIDS 7.1 Introduction Transmsson of HIV through njectng drug use accounts for the majorty of new nfectons n: Russa, Ukrane, Central Asa, some of Eastern Europe, South East Asa, North Afrca, Iran, Afghanstan, Pakstan, Nepal, Indonesa, Portugal and the Southern Cone of Latn Amerca. People at rsk of becomng HIV postve through njecton drug use are often among the poorest and most margnalsed sectons of socety: ethnc mnortes, unemployed, youth, mgrants, and sex workers. Addtonally - although there has been lttle or no research to address ths - there are potental nteractons between njecton and non-njecton recreatonal drugs, substtuton therapes and ARVs. 7 HIV i-Base: basc tranng for advocates S7:92 January 2008 Secton 7: Drug users and ARVs www.-Base.nfo 7.2 Aims for Section 7 Ths secton provdes an overvew of three key areas: • • • Belefs and realtes around treatment for drug users wth HIV Known and potental nteractons between recreatonal drugs and ARVs Known and potental nteractons wth methadone 7.3 General questions Why are drug users sometimes excluded from ARV treatment programmes? In many countres drug users are routnely excluded from ARV treatment programmes due to wdespread belef that they are less lkely to be adherent to treatment and less lkely to have a good response to treatment. Reluctance to offer ARV to drug users ncludes not only njecton drug users (IDUs), but also those on medcally prescrbed substtuton treatment such as methadone, users of non-njecton drugs, and former drug users. Is this appropriate? No. Belefs that drug users are non-adherent and untreatable are based on prejudce rather than scence. However, several studes suggest that drug users—partcularly when HIV treatment s delvered wth adherence, socal and medcal support—can acheve hgh levels of adherence and benefit from treatment just lke any other group of people wth HIV. • • • A large Western European study of people recevng ARVs found no sgnficant dfference between IDUs and non-drug users n CD4 or treatment response. Another study n Canada found that drug users who were adherent to treatment ganed the same ncreases n CD4 count as adherent non-drug users. In an Amercan moble syrnge exchange programme, 77% of drug users offered peer support along wth ARVs acheved reducton of vral load to less than 400 copes/ml and a 25% ncrease n CD4 after sx months. A French study of people recevng ARVs found that those also recevng buprenorphne acheved hgher levels of adherence (78.1%) than ether former drug users (65.5%) or actve IDUs not on buprenorphne (42.1%). • 7 HIV i-Base: basc tranng for advocates S7:93 January 2008 Secton 7: Drug users and ARVs www.-Base.nfo 7.4 Comprehensive and accessible care Includng as many health and socal servces as possble at a sngle ste has been shown to mprove both adherence and treatment outcomes for IDUs. Drug users are often unwllng to come forward, and there s a need for approprate support. Servces need to be located somewhere accessble to IDUs and wthn the HIV clnc settng. Comprehensve, mult dscplnary servces should nclude: • • • • • • • • • Access to ARVs Access to substtuton therapy: methadone or buprenorphne OI prophylaxs and treatment Accessble, non-judgemental healthcare team Needle exchange Adherence support and counsellng Strong lnks wth communty based programmes Food programmes and publc transport Outreach strateges 7.5 Interactions between recreational drugs and antiretrovirals There s much research and nformaton about nteractons between antretrovrals and other prescrbed medcatons, but lttle relable nformaton about nteractons between ARVs and recreatonal drugs. In 1996 a young HIV postve Brtsh man ded after takng ecstasy whle usng rtonavr. Hs death was caused by an overdose, and the level of ecstasy n hs blood was nearly ten tmes the level that s expected to cause serous toxc effects, e roughly the level after takng 22 ecstasy tablets. The patent had taken ecstasy prevously wth no such ll effects. Ths was the first tme that he had taken ecstasy snce addng rtonavr – taken full dose e 600mg twce daly – to hs ARV combnaton, whch s why hs doctors concluded that ths nteracton was the culprt. Followng nterventons by actvsts, the company – Abbott - produced some theoretcal nteracton nformaton for rtonavr and commonly used recreatonal drugs. Predcted nteractons wth rtonavr and street drugs: • • • • 2 to 3 fold ncrease n ecstasy levels About 50% decrease n blood levels of heron 2 to 3 fold ncrease n levels of amphetamnes No serous nteractons wth cocane Note: ths nformaton s based on usng full dose rtonavr; ths drug s now most commonly used to boost other protease nhbtors. 7 HIV i-Base: basc tranng for advocates S7:94 January 2008 Secton 7: Drug users and ARVs www.-Base.nfo 7.6 Why this theoretical information is not as useful as controlled interaction studies in humans? Because these drugs are llegal, predcted nteractons are not based on studes n humans but based on theory, experments n test tubes (n vtro) or anmal studes. There are a number of dfficultes both wth conductng proper studes and usng the theoretcal nformaton: • Clncal trals usng llegal drugs would requre permsson from the (Amercan) government, whch has been exceedngly reluctant to allow such studes for fear of beng perceved as “soft on drugs”. Fndng supples of pure drugs would, n some cases, be dfficult. There are no approved versons of drugs such as cocane. For legal and ethcal reasons, drug companes are unwllng to manufacture test versons of such drugs n ther own laboratores, even f the government granted permsson. Illegal drugs are seldom pure, are often contamnated by other substances, and may contan very lttle or none of the actual ngredent. Illegal drugs rarely have standardsed doses: what could be a relatvely mnor nteracton at one dose could be serous at another. There s lttle financal ncentve for drugs companes to do ths work. Some protease nhbtors have been found to have effects n real lfe opposte to those predcted n the test tube (eg, there have been nstances of decreased methadone levels n human users where test tube experments had predcted such levels would ncrease). Manufacturers are concerned about legal lablty should they offer advce based on uncertan or potentally ncomplete nformaton. • • • • • • 7 HIV i-Base: basc tranng for advocates S7:95 January 2008 Secton 7: Drug users and ARVs www.-Base.nfo 7.7 Interactions with other ARVs All protease nhbtors are processed by the body n a smlar way to rtonavr, as s the NNRTI efavrenz, so there s potental for nteracton wth any of these drugs. A comprehensve overvew summarsng nteractons between ARVs and recreatonal drugs (and methadone) lsts the followng potental nteractons and observed nteractons from case studes and makes recommendatons. See Table 1 n Secton 7.9. Ecstasy Potental for an nteracton wth PIs or efavrenz. Advsed to take approprate precautons: use 25% of the usual amount of ecstasy, take breaks from dancng, ensure rave or party has medcal team on ste, drnk lots of water and avod combnng wth alcohol. Other amphetamines – Potentally dangerous nteractons wth rtonavr and ths combnaton should be avoded f possble. GHB KETAMINE Potental nteracton wth PIs (especally rtonavr) and possbly efavrenz. There are no studes or reports descrbng nteractons between ketamne and antretrovral agents. People usng PIs may be at rsk for ketamne toxcty due to drug accumulaton. PCP (angel dust) Potental that use of PCP wth PIs, and possbly efavrenz may result n elevated PCP concentratons and resultant toxcty. People usng PCP who are also recevng treatment wth ARVs should be cautoned to use less than what they would normally use gven the potental for a drug nteracton. LSD It s not very clear how ths drug works, therefore antcpatng drug nteractons wth LSD s extremely dfficult. People who use LSD recreatonally and who use ARVs should be warned about the possblty of an nteracton and to be famlar wth sgns of LSD toxcty, and perhaps consder usng a smaller amount than normal. Interactons between cocane and antretrovrals have not been descrbed. It s thought that nteractons wth nevrapne or efavrenz may possble ncrease the rsk of lver toxcty but there s no research to support ths. There may be concern that heron s more rapdly metabolzed producng symptoms of wthdrawal when used wth PIs and efavrenz. Cocaine Heroin 7 HIV i-Base: basc tranng for advocates S7:96 January 2008 Secton 7: Drug users and ARVs www.-Base.nfo 7.8 Interactions with methadone There have been more studes of nteractons between ARVs and methadone. • People usng methadone and efavrenz or nevrapne wll have a reduced dose of methadone (of up to 60% n blood concentraton) and may requre an ncrease n ther methadone dose to overcome symptoms of methadone wthdrawal. There was a decrease of methadone of 36% n a human study of nteracton wth rtonavr. Ths was nterestng as a prevous study n the test tube found a 30% ncrease n methadone. Reduced concentratons of methadone have been found wth PIs nelfinavr and lopnavr/rtonavr. Some people may need a dose ncrease of methadone. AZT concentratons are ncreased by approxmately 2-fold and so a dose reducton of 50% of ths drug s recommended wth methadone. In contrast, methadone appears to decrease concentratons of d4T and ddI – there are currently no gudelnes for dose adjustment. • • • • Reduced methadone concentratons are not always accompaned by symptoms of wthdrawal. It can be dfficult to dstngush between symptoms of ARV toxcty and symptoms of wthdrawal (eg nausea, vomtng). It s lkely that symptoms that develop wthn 2-3 days may be due to ARV toxcty, and those that develop after 6 days are more lkely to be assocated wth wthdrawal. 7 HIV i-Base: basc tranng for advocates S7:97 January 2008 Secton 7: Drug users and ARVs www.-Base.nfo 7.9 Drug Table 1 – Interactions Between Antiretrovirals and Rave Drugs Metabolsm Actual/ Theoretcal Interacton Possble _ concentraton wth rtonavr Potental Sgnficance Hypertenson, hypertherma, sezures, arrhythmas, tachycarda, tachypnea Recommendaton Amphetamnes CYPD6 Avod combnaton wth rtonavr f possble: alternatvely, start wth 25-50% of ntal amount of amphetamne used Use cautously wth CYP450 nhbtors (.e. PIs, delavrdne, efavrenz,): become aware of sgns/ symptoms of GHB toxcty GHB Expred breath as CO2 : first pass metabolsm Possble ncreased concentratons/ prolonged effect wth antretrovrals, expecally rtonavr 1 case of GHB toxcty wth rtonavr/ saqunavr: myoclonc or sezure actvsty, bradycarda, respratory depresson, loss of conscusness Respratory depresson, loss of conscousness, hallucnatons Ketamne CYP2B6 (man) 3A, 2C9 (both to lesser extent) Possble ncreased concentraton wth antretrovrals, especally rtonavr, nelfinavr and efavrenz Possble ncreased LSD concentraton Use cautously wth CYP450 nhbtors, especally rtonavr nelfinavr, and efavrenz: become aware of sgns/symptoms of ketamne toxcty Use cautously wth CYP450 nhbtors; become aware of sgns/symptoms of LSD toxcty Avod combnaton wth rtonavr f possble; alternatvely use 25% - 50% of usual amount and watch for sgns of MDMA toxcty; stay well hydrated, avod alcohol Use cautously wth CYP450 nhbtors; become aware of sgns/symptoms of PCP toxcty LSD Unknown Hallucnatons, agtaton, psychoss, flashbacks MDMA, Ecstasy CYP2D6 (man) 1A2, 2B6, 3A4 (to lesser extent) Possble ncrease wth rtonavr, other PIs, efavrenz 1 death reported; hyponatrema, hypertherma, arrhythmas, tremor, hyperreflexa, sweatng, sezures, tachycarda, rhabdomyolyss Sezures, hypertenson, rhabdomyolyss, hypertherma PCP CYP3A, CYP2C11, nhbts CYP2B1 Possble ncreased concentratons wth antretrovrals 7 From: T Antonou and A Ln-n Tseng. Interactons Between Recreatonal Drugs and Antretrovral Agents. The Annals of Pharmacotherapy. 2002, October;Volume 36 HIV i-Base: basc tranng for advocates S7:98 January 2008 Secton 7: Drug users and ARVs www.-Base.nfo 7.10 Questions: Section 7 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Why are drug users frequently excluded from ARV treatment? Is ths based on scentfic evdence? What treatment and servces would be deally ncluded n a system of comprehensve care for IDU? Is there an nteracton between rtonavr and ecstasy? Is there an nteracton between rtonavr and heron? Is there an nteracton between efavrenz and methadone? What s dose changes, f any, are recommended n each case? Is there an nteracton between efavrenz and AZT? What s recommended? How could you dstngush between symptoms caused by ARVs toxcty and symptoms of drug wthdrawal? 7 HIV i-Base: basc tranng for advocates S7:99 January 2008 Secton 7: Drug users and ARVs www.-Base.nfo 7.11 Course evaluation of Section 7 Please take a few mnutes to complete ths evaluaton. Any comments are apprecated, ncludng on the usefulness of the evaluaton as we can develop ths nto an onlne resource. Session 7 How much of the nformaton was new? None How useful was the source materal? Very 1 1 2 2 3 3 4 4 5 5 All Not How much support tme dd you need n 1-2-1 questons? Were you gven enough support for ths secton? Dd you find better nternet stes for nformaton, f so, whch ones? Dd the questons relate to the nformaton you found yourself? What was your pass rate? St the test agan n one week to see how much you remember. Dd your pass rate mprove? 7 HIV i-Base: basc tranng for advocates S7:100 January 2008