HIV-related opportunistic diseases - · PDF fileHIV-related opportunistic diseases: UNAIDS...

UNAIDSTechnical update

October 1998

UNAIDS Best Practice Collection

HIV-relatedopportunisticdiseases

At a Glance

2October 1998 HIV-related opportunistic diseases: UNAIDS Technical Update

UNAIDS Best Practice materials

The Joint United NationsProgramme on HIV/AIDS (UNAIDS)is preparing materials on subjectsof relevance to HIV infection andAIDS, the causes and consequencesof the epidemic, and best practicesin AIDS prevention, care andsupport. A Best Practice Collectionon any one subject typicallyincludes a short publication forjournalists and community leaders(Point of View); a technical summaryof the issues, challenges andsolutions (Technical Update); casestudies from around the world (BestPractice Case Studies); a set ofpresentation graphics; and a listingof key materials (reports, articles,books, audiovisuals, etc.) on thesubject. These documents areupdated as necessary.

Technical Updates and Pointsof View are being published inEnglish, French, Russian andSpanish. Single copies of BestPractice materials are availablefree from UNAIDS InformationCentres. To find the closest one,visit UNAIDS on the Internet(http://www.unaids.org), contactUNAIDS by email ([email protected])or telephone (+41 22 791 4651),or write to the UNAIDS InformationCentre, 20 Avenue Appia,1211 Geneva 27, Switzerland.

Opportunistic diseases in a person with HIV are the products of twothings: the person’s lack of immune defences caused by the virus,and the presence of microbes and other pathogens in our everydayenvironment.

A partial list of the world’s most common opportunistic diseasesand diseases includes:

• bacterial diseases such as tuberculosis (TB, caused by Mycobacteriumtuberculosis), Mycobacterium avium complex disease (MAC), bacterialpneumonia and septicaemia (“blood poisoning”)

• protozoal diseases such as Pneumocystis carinii pneumonia (PCP),toxoplasmosis, microsporidiosis, cryptosporidiosis, isosporiasis andleishmaniasis

• fungal diseases such as candidiasis, cryptococcosis (cryptococcalmeningitis (CRM)) and penicilliosis

• viral diseases such as those caused by cytomegalovirus (CMV),herpes simplex and herpes zoster virus

• HIV-associated malignancies such as Kaposi sarcoma, lymphomaand squamous cell carcinoma.

Effective intervention against opportunistic diseases requires not onlythe appropriate drug or other medications for a given medical condition,but also the infrastructure necessary to diagnose the condition, monitorthe intervention, and counsel patients. As well, use of drugs and testsmust be supported by proper storage, handling and administrativeprocedures.

The main challenge of choosing between interventions is to alleviatethe morbidity and suffering of those in need while not exceeding thefinancial and technical capabilities of the health system. Unfortunately,these choices often need to be made without the help of formalcost-benefit and cost-effectiveness analyses. This is partly becausethe information needed to calculate costs is difficult to collect, butalso because benefits other than short-term improvements in qualityof life are not well understood or easily quantified.

In places where resources are very scarce, priority should be given tohealth needs shared by most or all of the population, including thosewho are HIV-infected. Examples are drugs to relieve pain in terminalpatients—including those with AIDS—or for TB. Drugs to treat andprevent TB have a high overall value to society in many countriesbecause they (a) benefit people affected by two epidemics (HIV/AIDSand TB), (b) are proven effective and (c) are relatively inexpensivegiven the number of people who can benefit.

Only a few opportunistic diseases and symptoms such as oropharyngealand vaginal candidiasis (“thrush”) or herpes zoster and herpes simplexcan be managed effectively through home-based care. Most otheropportunistic diseases require diagnosis and treatment which arebeyond the capabilities of most community-based groups and NGOs.

For conditions that can be treated only at a very high cost, the public-health rationale for treatment is weaker, and humanitarian or equityconsiderations become more important. Examples of such conditionsare CMV, MAC, cryptococcal meningitis (CRM), penicilliosis and rarersystemic mycoses.

HIV-related opportunistic diseases:UNAIDS Technical Update.October 1998.I. UNAIDS II. Series1. AIDS-related opportunistic

infections—drug therapy2. AIDS-related opportunistic

infections—diagnosis3. Prevalence4. Drug therapy—economics5. Diagnosic services6. Cost of illness7. Health prioritiesUNAIDS, Geneva

WC 503.5

3HIV-related opportunistic diseases: UNAIDS Technical Update October 1998

Background

People with advanced HIV infection are vulnerable to infections or malignancies that are called“opportunistic” because they take advantage of the opportunity offered by a weakened immunesystem. Various treatments and prophylaxis—some simple and low-cost, others highly complexand expensive—exist to counter the most common opportunistic diseases, but delivery systems andfunding are insufficient in many parts of the world to ensure their universal use.

The worldwide distribution ofopportunistic diseases is highlyvaried. Table 1 shows data on theirdistribution in six countries fromAfrica, the Americas, and South-East Asia. Like the following briefoverview of the most commondiseases and the interventionsavailable for their treatmentor prevention, the table is onlyintended to give a sense of thewide differences from countryto country.

Table 2 provides a comparison ofcosts of treatment and prophylaxisfor the most common opportunisticdiseases.

Candidiasis

The two main types of candidiasisare localized disease (of the mouthand throat, and of the vagina),and systemic disease (of theoesophagus, and disseminateddisease). The mouth and throatvariant (oropharyngeal candidiasisor OPC) is believed to occur atleast once in the lifetime in allHIV-infected patients.

While OPC is not a cause of death,it causes oral pain and makesswallowing difficult. The symptomof oesophageal candidiasis is painin the chest that increases withswallowing, and difficulty inswallowing. Disseminatedcandidiasis causes fever andsymptoms in the organs affected bythe disease (for example, blind-ness when it affects the eyes).

Localized disease is treated firstwith relatively inexpensive topicaldrugs such as nystatin, miconazole,or clotrimazole. Systemic anti-fungals agents are usually givenonly when topical therapy fails.

Systemic candidiasis requirestreatment with systemic antifungalagents such as ketoconazole,

itraconazole, fluconazole oramphotericin B. A two-weekcourse of ketoconazole 200 mgcosts US$ 5.53. Other azoleantifungal agents are not availablethrough generics suppliers, and aremuch more expensive.

Cryptococcosis

Systemic mycoses such as crypto-coccosis probably cause about5% of all HIV-associated deathsworldwide. Cryptococcosis mostoften appears as meningitis, andoccasionally as pulmonary ordisseminated disease. Cryptococcalmeningitis (CRM) is the mostfrequent systemic fungal infectionin HIV-infected persons. Withouttreatment, life expectancy isprobably less than a month.

Cryptococcosis is relatively easyto diagnose. However, its treat-ment (either amphotericin B withor without flucytosine, or in mildcases with oral fluconazole) andsecondary chemoprophylaxis areoften impossible in developingcountries because of the highcost and limited availability ofthe drugs required.

Cytomegalovirus infection (CMV)

Estimates of the incidence of CMVdisease vary considerably betweengeographical locations, but CMVcauses significant suffering in HIV-infected persons worldwide.Symptoms include fever anddiarrhoea from CMV colitis, dyspnoeafrom CMV pneumonitis, andblindness caused by CMV retinitis.

Treatment aims to alleviatesymptoms, and to prevent blindness,rather than provide a cure. Thedrugs currently used are ganciclovirand foscarnet, with cidofovir whenthe first two have failed. Theyhave high toxicity and limited

efficacy at a relatively high cost(which is increased by the need forclose monitoring), and are notincluded in the WHO essentialdrugs list.

Herpes simplexand Herpes zoster

Herpes simplex virus infection(HSV, which causes sores aroundthe mouth and genitals) and herpeszoster virus infection (“zonal” herpes)are not life-threatening but can beextremely painful. Both occurfrequently in HIV-infected persons,but as they are not consideredAIDS-defining conditions there arefew data about their incidence.Note, however, that both cancause encephalitis, which can belife-threatening.

Treatment with aciclovir is onlymarginally effective in herpeszoster but is sometimes dramaticin HIV-associated herpes simplexwith extensive ulceration. Acicloviris expensive, costing US$ 45.82and US$ 170.18 for 5-day herpessimplex and 7-day herpes zosterregimens respectively. However,its cost is likely to decrease whenit is no longer protected by patent,as is the case in the United Kingdomwhere generic aciclovir is available.Aciclovir can also be used to treatencephalitis at a cost of US$ 1282.76for a ten-day intravenous regimen.

Kaposi sarcomaHIV-associated Kaposi sarcomacauses dark blue lesions whichcan occur in a variety of locationsincluding the skin, mucousmembranes, gastrointestinal tract,lungs or lymph nodes. The lesionsusually appear early in the courseof HIV infection.

Treatment depends on the lesions’symptoms and location. For locallesions, injection therapy with


Background

vinblastine has been used withsome success. Radiotherapy canalso be used, especially in hard-to-reach sites such as the innermouth, eyes, face and soles ofthe feet. For severe widespreaddisease, systemic chemotherapyis the preferred treatment.

Most drugs for the chemotherapyof Kaposi sarcoma are includedin the WHO essential drugs list.However, since internationalgeneric drug suppliers appearto offer only vincristine andmethotrexate, the availabilityof drugs to treat the disease islimited in developing countries.

Leishmaniasis

Leishmaniasis is transmitted bysandflies and currently affectssome 12 million people in 88countries. The most serious of itsfour forms is visceral leishmaniasis(VL)—also known as kala azar—which is characterized by irregularbouts of fever, substantial weightloss, swelling of the spleen andliver, and anaemia (occasionallyserious). Recently, there has beenan increase in overlapping of VLand HIV infection. Treatment withpentavalent antimony is relativelyexpensive, partly because of thecost of drugs but also becausehospital admission is recommended(in milder cases, trained healthworkers may administer theinjections or infusions at a patient’shome). Even with optimal treatment,mean survival time with this co-infection is only 12 months.

Lymphoma and squamouscell carcinoma

The treatment of lymphoma inHIV-infected persons is controver-sial. Survival is not greatly increasedby expensive chemotherapy,and quality of life is poor duringtreatment. Drugs used in theseregimens are included in the WHOessential drugs list and ought to beavailable, but this is often not thecase as they are not often stockedby generic drugs distributors. Also,

only sophisticated health-caresystems can handle them safely.

Mycobacterium avium complexdisease (MAC)

MAC disease appears to berelatively rare in Africa, butelsewhere it occurs in around 5%of persons with AIDS. Symptomsinclude fever, weight loss, nightsweats, diarrhoea, and wasting.

Recommended drugs for pro-phylaxis include azithromycin,clarithromycin and rifabutin.For treatment, clarithromycin/ethambutol/rifabutin combinationtherapy is the only regimen thathas been documented to increaselife expectancy; even so, in practicea two-drug regimen of a macrolideantibiotic and ethambutol is oftenused as it reduces the potential forboth drug interactions and toxicityand it decreases cost. With theexception of ethambutol, noneof these drugs is included in theWHO essential drugs list becauseof their high cost and the fact theydo not cure MAC.

Pneumocystis cariniipneumonia (PCP)

PCP is the most frequent HIV-associated opportunistic infectionin industrialized countries, butappears to be less frequent inAfrica. The symptoms are mainlypneumonia along with fever andrespiratory symptoms such as drycough, chest pain and dyspnoea.Definitive diagnosis requires micro-scopy of bodily tissues or fluids.

Severe cases of PCP are initiallytreated intravenously withtrimethoprim-sulfamethoxazole(TMP-SMZ), or clindamycin andoral primaquine. Mild cases canbe treated with oral TMP-SMZthroughout. With both of theseregimens, toxicity (notablyallergic-type reactions) oftenrequires changes in therapy.

Prevention of PCP is stronglyrecommended for HIV-infectedpersons with significant immunecompromise wherever PCP is a

significant health problem for HIV-infected persons, and also aftertheir first episode of PCP. Preventingand treating PCP need not be veryexpensive: use of no-brand genericproducts can reduce the cost ofdrugs for TMP-SMZ prophylaxis tounder US$ 12.00 per year.

Toxoplasmosis

This disease is found in about 5%of AIDS patients in the USA, buta greater proportion in Europe.Reliable data on its incidence indeveloping countries are lacking,but studies have demonstratedthat the disease does occur ina significant proportion of AIDSpatients. In HIV-infected personstoxoplasmosis mainly appears asencephalitis or as disseminateddisease. Diagnosis of toxoplas-mosis is by CT scan or MRI scan.Brain biopsies are rarely carriedout. If toxoplasmosis is stronglysuspected, patients are more likelyto be given a trial of therapy, andonly if they do not respond to thistherapy is a brain biopsy considered.

The disease is treated withpyrimethamine plus sulfadiazine.Primary chemoprophylaxis for PCPwith TMP-SMZ, or with dapsoneand pyrimethamine, offers protectionagainst toxoplasmosis as well.Secondary chemoprophylaxis iswith pyrimethamine plus sulfadiazineand leucovorin. While pyrimethamineis widely available, the drugcombination is toxic to bone marrowat the dosage recommended forprophylaxis. Prophylactic leucovorin(also called calcium folinate), whichis given to prevent the side effectsof pyrimethamine and as secondaryprophylaxis, is very expensive.

Tuberculosis

Tuberculosis (TB) is the leadingHIV-associated opportunisticdisease in developing countries.

The DOTS (directly observed,short course) treatment strategyrecommended by WHO treats TBin HIV-infected persons as effectivelyas it treats those without the virus.


A complete cure takes 6 to 8 monthsand uses a combination of anti-biotics. In addition to curing theindividual it also prevents furtherspread of the disease to others.This is why treating infectious casesof TB has important benefits forsociety as a whole, and is themainstay of the WHO’s TB controlstrategy. (See Tuberculosis and AIDSin the UNAIDS Best PracticeCollection for more information.)Isoniazid preventive therapy isrecommended as a health-preserving

Background

measure for HIV-infected personsat risk of TB, such as those witha positive TB skin test or who areliving in areas where the disease isendemic. TB prophylaxis has beenshown to increase the survival ofHIV-infected persons at risk of TB(see O’Brien and Perriëns in theSelected Key Materials). The casefor public funding of TB prophylaxisby developing countries awaitsconfirmation of its cost-effectivenesscompared to treating infectiousTB cases. However, given the low

incremental cost of isoniazid therapy—US$ 5.15 for a year’s preventionaccording to the 1996 Drug andPrice Independent Guide—once aperson is identified as HIV-infected,there is a strong case to provideTB prophylaxis for HIV-infectedpersons whenever financiallyfeasible. (See WHO Policy Statementon Preventive Therapy againstTuberculosis in People Living withHIV in the Selected Key Materials.)

Table 1. AIDS-defining opportunistic diseases: Prevalence in six countries1

Opportunistic disease Côte Brazil Mexico Thailand USA Zaire2 Infrastructure or malignancy d’Ivoire needed 3

Aspergillosis 3% 3–7% advanced

Atypical mycobacteriosis 4% 5–6% 2% 4% advanced

Bacteraemia 7% 4% advanced

Candidiasis 24% 5% 30% 11% 13% minimal

CMV 26% 5% 65–69% 4% 5% 13% advanced

Cryptococcosis 5% 5% 7–11% 2% 7% 19% medium

Cryptosporidiosis – Isosporiasis 4% 14% 8% 4% 6.2% <2% advanced

Enteritis, non-specific 4 12% 13% minimal

Herpes (systemic) 6% 5% 10% 4% minimal

Histoplasmosis 3% 5–10% 8% <2% advanced

Kaposi sarcoma 13% 5% 30–43% 21% 16% medium

Lymphoma 4% 4% 10% 0.7% advanced

Nocardiosis 5% <2% advanced

Penicilliosis 4–25% advanced

Progressive multifocal leukoencepha-lopathy (PML) or HIV encephalitis 6% 11% 7% 0.6% advanced

Pneumocystis carinii pneumonia 4% 22% 24% 26% 64% <2% medium

Pneumonia 5% 16% 34% advanced

Toxoplasmosis 21% 14–34% 17% 2% 3% 11% advanced

Tuberculosis 54% 41% 28% 20% 3% 41% medium

Others 9% 9%

Source: Perriëns J, Clinical aspects of HIV-related opportunistic diseases in Africa: tuberculosis and candidiasis.University of Gent, 1994.1 Data from autopsy studies, except Brazil (one autopsy and one clinical series), Thailand (two clinical series)

and USA (one clinical series).2 Democratic Republic of Congo.3 Infrastructure needed to diagnose, treat4 Clinical diagnosis for non-specific enteritis does not identify the cause. It permits treatment to be carried out,

but not necessarily the most effective one.


Background

Table 2. Comparative costs of treatment and prophylaxis for common opportunistic diseases in adults

Opportunistic Drug and dose Duration Cost of treatment (in $) Source (b)

disease course or per-year cost (a)

Candidiasis Ketoconazole 200 mg once a day 14 days 5.53 IDPIGFluconazole 50 mg once a day 07 days 26.34 BNFItraconazole liquid 100 mg twice a day 07 days 82.92 BNF

Cryptococcosis Amphotericin B 1 mg/kg daily +/- 14 days 164Acute treatment Flucytosine 100 mg/kg/day orally 14 days price not available BNF

Fluconazole 800 mg orally for 2 days see dose 662 BNFfollowed by 600 mg daily

Cryptococcosis Amphotericin 1 mg/kg/day 8 weeks 657 BNFConsolidation Fluconazole 400 mg/day 8 weeks 1685 BNFtreatment Itraconazole 400 mg/day (liquid) 8 weeks 1238 BNF

Cryptococcosis Fluconazole 200 mg once a day Long term 5493 p.a. BNFSecondary prophylaxis Amphotericin 50 mg twice a week Long term 610 p.a. BNF

Cytomegalovirus Ganciclovir 1 g 3 times a day orally Long-term 21 968 BNFinfection Ganciclovir 5 mg/kg once a day Long-term 12 358 BNFProphylaxis Foscarnet 90 mg/kg once a day Long-term 18 148 BNF

Cidofovir 5 mg/kg/14 days Long-term 29 071(c)

Cytomegalovirus Ganciclovir 5 mg/kg twice a day 14 days 959 BNFinfection Foscarnet 90 mg/kg twice a day 14 days 1160 BNFTreatment Cidofovir 5 mg/kg once a week 14 days 2236 (c)

Herpes simplex Simplex: Aciclovir 200 mg 5 times a day 05 days 45.82(d) BNFand zoster Zoster: Aciclovir 800 mg 5 times a day 07 days 170(d) BNF

Encephalitis: Aciclovir 10 mg/kg IV 3 times a day 10 days 1283(d) BNF

Kaposi sarcoma Bleomycin 15 units and vincristine 2mg 1 cycle 25.84 BNFevery three weeks. 33.58 BNF

Mycobacterium avium Azithromycin 1.25 g once a week (American dose 1.2 g) Long-term 923 p.a. BNFcomplex disease Clarithromycin 500 mg twice a day Long-term 1860 p.a. BNFProphylaxis Rifabutin 300 mg once a day Long-term 3176 p.a. BNF

Mycobacterium avium Clarithromycin 500 mg twice a day Long-term 1860 p.a. BNFcomplex disease + ethambutol 15 mg/kg once a day Long-term 34.68 p.a. IDPIGTreatment +/- rifabutin 450 mg once a day Long-term 4764 p.a. BNF

Mycobacterium Isoniazid 300 mg daily 1 year 5.15 p.a. IDPIGtuberculosis Prophylaxis

Mycobacterium Rifampicin 600 mg once a day 6 months Combined IDPIGtuberculosis Isoniazid 300 mg once a day 6 months 22.72 +Treatment Pyrazinamide 2 g once a day 2 months 11.11/course IDPIG

Pneumocystis carinii Trimethoprim-sulfamethoxazole 960 mg once a day Long-term 11.39 p.a. IDPIGpneumonia Dapsone 100 mg a day Long-term 3.58 p.a. IDPIGProphylaxis Dapsone 100 mg a day and pyrimethamine 25 mg Long-term 10.83 p.a. IDPIG

three times a week

Pneumocystis carinii Trimethoprim-sulfamethoxazole 90 mg/kg/day 21 days PO 3.93 IDPIGpneumonia IV: 611 BNFTreatment Clindamycin 600 mg four times a day 21 days PO 253 BNF

and primaquine 15 mg once a day IV 1370 BNFPO 0.11 IDPIG


(a) PO—orally; IV—intravenously; p.a. per annum

(b) Sources: IDPIG: International Drug Price Indicator Guide 1996, and BNF: British National FormularyNumber 33 (March 1997)

(c) Middlesex Hospital Price (recently released medication not yet in the BNF)

(d) Aciclovir prices given are for branded products, reduced generic prices not in the BNF yet

Doses calculated for an average 60 kg patient. If it is possible for intravenous vials to be used more than onceor the reconstituted solution kept, doses have been calculated as the number of milligrams for the treatmentcourse, and then converted into the number of vials (e.g. ganciclovir). When this is not possible, the number ofvials for each dose has been calculated (e.g. amphotericin 60 mg would require 2 x 50 mg vials/day).

Background

Table 2. (continued)

Opportunistic Drug and dose Duration Cost of treatment (in $) Source (b)

disease course or per-year cost (a)

Toxoplasmosis Sulfadiazine 2 g three times a day plus 6 weeks 217 BNFTreatment pyrimethamine 200 mg in divided 6 weeks 4.19 IDPIG

doses then 50 mg daily and calcium 6 weeks 244 BNFfolinate 15 mg daily (all oral)Clindamycin 600 mg orally four times 6 weeks 507+ BNFa day plus pyrimethamine and calcium 4.19 +folinate as above 244

Toxoplasmosis Sulfadiazine 1 g three times a day plus Long-term 944 p.a.+ BNFSecondary pyrimethamine 25 mg once a day and Long-term 16.97 p.a.+ IDPIGprophylaxis calcium folinate 15 mg once a day Long-term 2125 p.a. BNF

Clindamycin 450 mg three times a day Long-term 4411 p.a.+ BNFand pyrimethamine and calcium 16.97 p.a.+folinate as above 2125 p.a.


The Challenges

Lack of advocacyBecause of the large variety ofconditions related to HIV and thenumber of care options, prophylaxisand management of opportunisticdiseases (including their diagnosis,treatment and palliation) is a difficultissue to advocate for. Patients andtheir families may enthusiasticallylobby for access to a particulardrug they have heard about.However, it is harder to for themto inform themselves sufficientlyto advocate in an effective wayfor a full “package” of equipment,services, laboratory materials,testing kits and staff trainingneeded to deal with the full rangeof opportunistic diseases.

Representative organizationsmay have the same problem ofinsufficient knowledge, or theymay have too many other priorityissues to focus on this highly technicalone. Even medical personnel who,on a technical level, have a clearunderstanding of what is needed,often do not have the means ormotivation to turn this knowledgeinto effective advocacy.

In some places, it is difficult ordangerous for people living withHIV to carry out their own advocacyopenly, or for organizations to doit on their behalf.

Lack of infrastructureEffective intervention againstopportunistic diseases requires notonly the appropriate drug or othermedicament for a given medicalcondition, but also the infrastructurenecessary to diagnose the condition,monitor the intervention, and counselpatients. As well, use of drugs andtests must be supported by properstorage, handling and administrativeprocedures. (For a more detaileddiscussion of HIV-related drugs,see the Technical Update on Accessto Drugs. Also relevant to thisdiscussion is the Technical Updateon HIV Testing Methods.)

As can be seen in Table 1, the infra-structure required to prevent, diagnoseand manage opportunistic diseases

and malignancies can be classified(somewhat arbitrarily) in three levels:

• Minimal: diagnosis can be made byobservation of symptoms or use of asimple microscope; diagnostic, treat-ment and palliative procedures arenon-invasive; follow-up of patientsdoes not require highly trained staff.Relatively little investment in equip-ment is required. Successful diagnosis,treatment and palliation (including forterminal patients) chiefly require thatstaff have sufficient knowledge andexperience to recognize symptomsand prescribe drugs that are easilystored, along with equipment forsimple microscope work. Home-basedcare and community health initiativescan be very effective in deliveringtreatment and follow-up. Examplesare oral candidiasis and pulmonarytuberculosis, herpes, and cryptococcalmeningitis.

• Medium: diagnosis requires X-rayequipment or culture facilities, whilediagnostic and treatment proceduresrequire trained staff and well runlaboratories. Significant investmentin equipment and ongoing operatingcosts are required. Examplesare extra-pulmonary tuberculosis,cryptosporidiosis-isosporiasis, PCPand Kaposi sarcoma.

• Advanced: diagnosis requirementsinclude endoscopy and CT scanning;diagnosis and treatment requirehighly trained and specialized staff;investment in equipment and operatingcosts is high; patient follow-up maybe complex. Examples include toxo-plasmosis, MAC disease and CMV.

As one moves from level to level,costs and training requirementsincrease dramatically.

Lack of informationfor decision-makingTo estimate which interventions andwhat supporting infrastructure arerequired to handle HIV-relatedopportunistic infections and malignan-cies, decision makers need to know:

• What are the incidence rates ofthe HIV-related conditions in thearea under their responsibility?

• Which regimens are availableto treat or prevent the conditionsof interest, and at what cost?

• What are the non-drug costs ofdealing with opportunistic diseases(such as medical staff time, purchaseand operation of diagnostic equip-ment, storage and transportationof drugs, etc.)?

The main challenge of choosingbetween interventions is to alleviatethe morbidity and suffering ofthose in need while not exceedingthe financial and technicalcapabilities of the health system.

Unfortunately, these choices oftenneed to be made without the helpof formal cost-benefit and cost-effectiveness analyses. This is partlybecause, as described above, theinformation needed to calculatecosts is difficult to collect, but alsobecause benefits other than short-term improvements in qualityof life are not well understoodor easily quantified. For example,it has been demonstrated thatprophylaxis of MAC with azithromycincan lengthen survival, but it is stillnot clear exactly how much lifeexpectancy is lengthened with it.

The challenge of fairnessGiven the lack of complete epidemiol-ogical data in many regions andthe difficulties of formal cost-benefitand cost-effectiveness analysis,the process of choosing whichinterventions merit public fundingis frequently forced into lessmethodologically solid—and morepolitical—calculations than mosthealth administrators would like.This brings forward the additionalchallenge of ensuring equity andnon-discrimination in the decision-making process, and re-emphasizesthe need for informed advocacy.In places where resources are veryscarce, priority should be given tohealth needs shared by most or allof the population, including thosewho are HIV-infected. Examplesare drugs to relieve pain in terminalpatients and to treat or prevent TB.


The Responses

A complete response to the needscreated by HIV-related opportunisticdiseases requires a variety ofstakeholders to play their part.On the one hand, people infectedwith or affected by HIV mustbecome aware of (and believe in)the possibilities for managingopportunistic diseases if they areto advocate for them. On theother hand, health systems mustbe prepared to make decisionsabout what interventions can andshould be offered. In between,NGOs and community-basedorganizations can have a strongrole to play both in advocacy anddelivery of care.

Preventingopportunistic diseases

Interventions that prevent theoccurrence of opportunisticdiseases can result in significantgains in life expectancy and qualityof life among people living withHIV. Two useful sources for thosewishing more information on thisimportant subject are mentionedin the Selected Key Materials. InFrance, the book Prise en chargedes personnes atteintes par le VIH(Care for people with HIV) iswidely distributed to physiciansand presents a great deal ofpractical information on the subject.In the United States, guidelines onprevention of opportunistic diseasesare jointly published and updatedby the US Public Health Service(USPHS) and the Infectious DiseasesSociety of America (IDSA). Theseguidelines are also found on theInternet at http://www.thebody.com/cdcoiguide/guidelines1.html.

Mobilizing communities

In a variety of settings around theworld, community-based groupsand NGOs are working to providehome-based care for people withHIV/AIDS. However, it should berealized that only a fewopportunistic diseases andsymptoms such as oropharyngealand vaginal candidiasis or herpeszoster and herpes simplex can be

managed effectively through home-based care. Most opportunisticdiseases require Toxoplasmosisdiagnosis and treatment of acomplexity beyond the capabilitiesof most community-based groupsand NGOs.

Priorities for public spending

When faced with limited resources,as is the case for most health-caresystems, the best framework fordecision making is one that takesinto account both the costs and the“spinoff” value of interventions forHIV-related opportunistic diseases.The term “spinoff” means thatthe framework must not only valuethe benefits of a given interventionfor individual HIV-infected patients,but also the benefits for otherpeople—including those notinfected with HIV.

The clearest example of a high-priority public intervention againstopportunistic infection is probablythe diagnosis, treatment andprevention of tuberculosis. Evenwithout exact information on HIVprevalence or the cost-benefitratios of these interventions ina given setting, their overall valueto society can be accepted as highon several counts:• they benefit people affected by

or at risk from two epidemics:HIV/AIDS and TB;

• they are proven effective;• both the drug costs and

associated costs are relativelylow given the number of peoplereached by the intervention.

Even in societies with “minimal”resources and facilities, a basicpackage of palliative care should beavailable for persons living with HIV/AIDS, including terminal patients.

For conditions that can be treatedbut only at a very high cost, thedecision to be made is morecontroversial. Examples are CMV,MAC, fungal infections such ascryptococcal meningitis (CRM),penicilliosis and rarer systemicmycoses such as histoplasmosis

and coccidioidomycosis. All havevery high treatment and prophylaxiscosts. Governments should assesswhich of these diseases are commonin their population, and then decidewhether subsidizing the availabletherapies is warranted. In manycases the only affordable approachis to make available palliativedrugs that alleviate the sufferingcaused by these conditions.


© Joint United Nations Programme on HIV/AIDS 1998. All rights reserved. This publication may be freely reviewed, quoted, reproduced or translated, in part orin full, provided the source is acknowledged. It may not be sold or used in conjunction with commercial purposes without prior written approval from UNAIDS(contact: UNAIDS Information Centre, Geneva–see page 2.). The views expressed in documents by named authors are solely the responsibility of those authors.The designations employed and the presentation of the material in this work do not imply the expression of any opinion whatsoever on the part of UNAIDSconcerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers and boundaries. The mention ofspecific companies or of certain manufacturers' products do not imply that they are endorsed or recommended by UNAIDS in preference to others of a similarnature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

Selected Key Materials

Dormont PJ (ed). Prise en charge despersonnes atteintes par le VIH, 1996edition. Paris: Flammarion, 1996.This is a practical, compre-hensiveguide to management of HIV,published with the support of theFrench Ministry of Labour and SocialServices. It is widely distributed tophysicians in France.

Steward GJ (ed). Managing HIV.Sydney: The Australasian MedicalPublishing Company, 1996.Part 5 of this book provides acomprehensive overview of how HIV-related opportunistic diseases shouldbe diagnosed and treated.

U.S. Public Health Service (USPHS),Infectious Diseases Society ofAmerica (IDSA). Guidelines forthe Prevention of OpportunisticDiseases in Persons Infected WithHuman Immunodeficiency Virus:A Summary. Available on the Internetat http://www.thebody. com/cdc/oiguide/guidelines1.html. Thisoverview of prevention of HIV-related opportunistic infectionsincludes therapeutic recommend-ations and guidance on petownership, hygienic practices,and avoidance of environmental

exposure. A version specific to LatinAmerica and the Caribbean hasbeen published in Spanish.

Kaplan JE et al. Preventingopportunistic diseases in humanimmunodeficiency virus-infectedpersons: implications for thedeveloping world. American Journalof Tropical Medicine and Hygiene1996; 55(1):1–11. This discusseshow the USPHS/IDSA Guidelinescan/should be adapted to fitdeveloping country needs.

Leishmania and HIV: in gridlock.Geneva: WHO/UNAIDS, 1998(WHO/CTD/LEISH/98.9/UNAIDS).This document is aimed to helpdecision-makers shape and prioritizestrategies to deal with the growingthreat of leishmania/HIV co-infection.

Management Sciences for Health.Managing Drug Supply: The Selection,Procurement, Distribution, and Use ofPharmaceuticals (2nd edition). Boston:Kumarian Press, 1998.Comprehensive manual withpractical case studies on all aspectsof drug selection, procurement,distribution and use.

WHO Policy Statement on PreventiveTherapy against Tuberculosis inPeople Living with HIV. Geneva:WHO, August 1998.Recommendations to governmentsbased on a meeting of regionalexperts, including discussion of cost-benefit and cost-efficacy.

Marco M et al. The OI Report:A Critical View of the Treatment andProphylaxis of HIV-relatedOpportunistic Infections (version 2.0)New York: The Treatment ActionGroup (TAG), 1998.This report discusses opportunisticinfections since developmentof protease inhibitors. Includeschapters on bacterial infectionsand AIDS-related tuberculosis.

Van der Horst CM et al. Treatment ofcryptococcal meningitis associatedwith the acquired immunodeficiencysyndrome. New England Journalof Medicine, 1997, 337:15–21. Theauthors report on a trial testingtreatment of AIDS-related crypto-coccal meningitis using amphotericin Bplus flucytosine. The results includeincreased rate of cerebrospinal fluidsterilization and decreased mortality.

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