HIV/AIDS & Hepatitis HIV/AIDS & Hepatitis C: Contrasting C: Contrasting Pathways in Pathways in

Prevention and Prevention and TreatmentTreatment

Ronald P. Hattis, MD, MPHRonald P. Hattis, MD, MPHPresident, Beyond AIDS FoundationPresident, Beyond AIDS Foundation

delivered atdelivered at

Loma Linda UniversityLoma Linda UniversitySeptember 20, 2006September 20, 2006

Some interesting Some interesting contrasts between contrasts between hepatitis C and HIVhepatitis C and HIV

HEPATITIS CHEPATITIS C 1. Always reportable 1. Always reportable

by name in Californiaby name in California 2. No written consent 2. No written consent

needed for testingneeded for testing 3. About 4 million 3. About 4 million

infected in USinfected in US 4. Hardly any money 4. Hardly any money

for prevention andfor prevention and treatmenttreatment

HIVHIV 1. Not reportable by 1. Not reportable by

name until 2006name until 2006 2. Written consent 2. Written consent

needed for testingneeded for testing 3. About 1 million 3. About 1 million

infected in USinfected in US 4. Lots of money for 4. Lots of money for

prevention and prevention and treatmenttreatment

How could discrepancies be addressed How could discrepancies be addressed

for better prevention and treatment?for better prevention and treatment? If HIV/AIDS could be treated in a less If HIV/AIDS could be treated in a less

exceptional manner, techniques that have exceptional manner, techniques that have been successful in controlling syphilis and been successful in controlling syphilis and TB could be more easily applied (e.g., TB could be more easily applied (e.g., reporting, partner notification, routine reporting, partner notification, routine screening, and case management to screening, and case management to influence safe behavior)influence safe behavior)

If hepatitis C could achieve attention and If hepatitis C could achieve attention and funding on the scope of HIV/AIDS, control funding on the scope of HIV/AIDS, control and treatment efforts could be more and treatment efforts could be more proportional to the magnitude of the proportional to the magnitude of the problemproblem

Interactions between HIV Interactions between HIV and hepatitis Cand hepatitis C

Many drug users with HIV also acquired Many drug users with HIV also acquired hepatitis C through the same means hepatitis C through the same means (needle sharing).(needle sharing).

Since hepatitis C is so much more Since hepatitis C is so much more prevalent, a high proportion of HIV prevalent, a high proportion of HIV patients also have hepatitis C, but the patients also have hepatitis C, but the proportion of hepatitis C patients with HIV proportion of hepatitis C patients with HIV is relatively small.is relatively small.

HIV promotes hepatitis C progression to HIV promotes hepatitis C progression to cirrhosis, cancer, and liver failure, so that cirrhosis, cancer, and liver failure, so that severe liver disease occurs earlier.severe liver disease occurs earlier.

Interactions between HIV Interactions between HIV and hepatitis C, contd.and hepatitis C, contd.

Hepatitis C also makes it harder to Hepatitis C also makes it harder to treat HIV, because many drugs must be treat HIV, because many drugs must be metabolized by the liver. Drugs used metabolized by the liver. Drugs used for HIV may further damage the liver.for HIV may further damage the liver.

Treatment recommendations for Treatment recommendations for hepatitis C are not changed by hepatitis C are not changed by presence of HIV, but hepatitis C presence of HIV, but hepatitis C treatment seems to be more effective treatment seems to be more effective in immune-competent individuals.in immune-competent individuals.

Interactions between HIV Interactions between HIV and hepatitis C, contd.and hepatitis C, contd.

HIV patients also infected with HIV patients also infected with hepatitis C are not as able to hepatitis C are not as able to suppress hepatitis C, and have suppress hepatitis C, and have larger numbers of hepatitis C larger numbers of hepatitis C viruses in their plasma and livers.viruses in their plasma and livers.

Hepatitis C may be more infectious Hepatitis C may be more infectious sexually and from mother to infant sexually and from mother to infant in HIV co-infected patients.in HIV co-infected patients.

Comparing the viruses: HIV and Comparing the viruses: HIV and HCVHCV

Both HIV and HCV are RNA virusesBoth HIV and HCV are RNA viruses– do most of their damage through insidious, do most of their damage through insidious,

chronic infection after long asymptomatic periods.chronic infection after long asymptomatic periods.

Both HIV and HCV mutate frequentlyBoth HIV and HCV mutate frequently– causing enough variability in surface proteins to causing enough variability in surface proteins to

evade antibody attacksevade antibody attacks– antibodies are a marker for infection rather than antibodies are a marker for infection rather than

evidence of immunity.evidence of immunity.

For hepatitis C, most transmission is by For hepatitis C, most transmission is by needle and only minimally by sexneedle and only minimally by sex

For HIV, most transmission is by sex and For HIV, most transmission is by sex and secondarily by needle.secondarily by needle.

Comparing the HIV and Comparing the HIV and hepatitis C epidemics in the hepatitis C epidemics in the

U.S.U.S. Incidence of hepatitis C in the U.S. is past its Incidence of hepatitis C in the U.S. is past its

peak, but the impact of eventual cirrhosis, liver peak, but the impact of eventual cirrhosis, liver failure, and liver cancer from already-infected failure, and liver cancer from already-infected persons will be immense.persons will be immense.

HIV incidence has been stable, but prevalence is HIV incidence has been stable, but prevalence is increasing, in part because of longer life spansincreasing, in part because of longer life spans

Supposing hepatitis C were only 20% as deadly Supposing hepatitis C were only 20% as deadly as HIV but the prevalence is 5 times higher, how as HIV but the prevalence is 5 times higher, how will the ultimate mortality compare?will the ultimate mortality compare?– Actual mortality will depend on effectiveness of future Actual mortality will depend on effectiveness of future

treatments as well as on courses of the epidemicstreatments as well as on courses of the epidemics

HIV at its Worst: HIV prevalence in five countries in sub-Saharan Africa

            South Botswana Namibia Lesotho

Swaziland Africa

Population (000s) 39,900 1,597 1,695 2,108980

Population 5-49 (000s) 20,982 786 795 1,000468

% of Total Popn. w/HIV 10.50% 18.20% 9.40% 11.40% 13.30%

HIV Infected People (000s) 4,200 290 160 240130

Adult Prev. Rate of HIV 20.00% 35.80% 19.50% 23.60%25.30%

% of HIV in Females 54.80% 51.20% 53.10% 54.20%51.50%

Pregnant Women HIV Prev. 19.20% 43.00% 25.90% N/A30.30%

AIDS Orphans (Living 370,952 54,943 53,023 29,469 10,705

Source: UNAIDS 2000 Update

OK, that’s Africa; how about OK, that’s Africa; how about the U.S. - Is HIV under control the U.S. - Is HIV under control here?here? Estimated 40,000 new cases Estimated 40,000 new cases

continue to occur yearlycontinue to occur yearly– Actually represents overlap of epidemic Actually represents overlap of epidemic

course in multiple sub-population groupscourse in multiple sub-population groups Some increasingSome increasing Some decreasing, but only because few Some decreasing, but only because few

susceptibles left and the long-infected die susceptibles left and the long-infected die out.out.

Recent resurgence of syphilis among Recent resurgence of syphilis among and accompanied by HIV infections and accompanied by HIV infections among young gay males.among young gay males.

Other ominous HIV trends in Other ominous HIV trends in U.S.U.S.

Published reports show infected men Published reports show infected men who are told their HIV viral loads are who are told their HIV viral loads are low or undetectable assume they are low or undetectable assume they are not infectious, and reduce safe not infectious, and reduce safe behavior.behavior.

Increases in “barebacking” and “bug-Increases in “barebacking” and “bug-chasing” (intentionally becoming chasing” (intentionally becoming infected) have been reported.infected) have been reported.

50% of new HIV cases are occurring 50% of new HIV cases are occurring in African-Americansin African-Americans..

Prevalence of HCV Prevalence of HCV (Hepatitis C Virus) Antibody (Hepatitis C Virus) Antibody

in U.S.in U.S. 1.8% of US population, ~ 4,000,000 (4 1.8% of US population, ~ 4,000,000 (4 times the prevalence of HIV)times the prevalence of HIV)– But up to 30% prevalence in jails and prisons But up to 30% prevalence in jails and prisons

(10 times the prevalence of HIV)(10 times the prevalence of HIV)

1% of population HCV RNA (+), ~ 2,700,0001% of population HCV RNA (+), ~ 2,700,000RaceRace– WhiteWhite 1.5% 1.5%– BlackBlack 3.2% 3.2%– Mexican 2.1%Mexican 2.1%

Highest prevalence in 30-49 year oldsHighest prevalence in 30-49 year olds

CDC. MMWR. 1998;47(RR-19):1-39.

Decline among Decline among transfusion recipientstransfusion recipients

Decline among Decline among injection-drug usersinjection-drug users

YearYear

55

1010

1515

2020

00

8282 8484 8585 8686 8787 8888 8989 9090 9191 9292 93938383 9494 9595 9696

Cases per Cases per 100,000100,000

Centers for Disease Control and Prevention. Unpublished data.Centers for Disease Control and Prevention. Unpublished data.

Estimated Incidence,Estimated Incidence,United States, 1982-1996United States, 1982-1996

Acute Hepatitis CAcute Hepatitis C

HIV Prevention MeasuresHIV Prevention Measures

(type 1)

Sources of hepatitis CSources of hepatitis C

AcquisitionAcquisition and Course Of and Course Of Hepatitis CHepatitis C

Genotype commonest in the US (type 1) Genotype commonest in the US (type 1) unfortunately unfortunately worstworst in prognosis and in prognosis and poorest in responsiveness to treatment.poorest in responsiveness to treatment.

Approximately 85-90% of infected persons Approximately 85-90% of infected persons become chronically infected. become chronically infected. – Remainder of infections resolve clinicallyRemainder of infections resolve clinically– Doubtful virus ever totally eradicated.Doubtful virus ever totally eradicated.

Course of Hepatitis C Course of Hepatitis C variablevariable– Severity of illness ranges from transient, self Severity of illness ranges from transient, self

limited and asymptomatic infection to a limited and asymptomatic infection to a chronic, progressive liver diseasechronic, progressive liver disease

Leads ultimately (usually >20 yrs.) to cirrhosis, HCC, Leads ultimately (usually >20 yrs.) to cirrhosis, HCC, or liver failureor liver failure

The escalating cost of hepatitis Chepatitis C

As with HIV, acute infection causes As with HIV, acute infection causes minimal mortality and patients are minimal mortality and patients are usually asymptomatic for yearsusually asymptomatic for years

Serious disease usually takes 20+ years, Serious disease usually takes 20+ years, vs. 10+ for HIVvs. 10+ for HIV

Late liver disease will increase as Late liver disease will increase as infections matureinfections mature– CirrhosisCirrhosis– Hepatocellular carcinoma (rarely without Hepatocellular carcinoma (rarely without

cirrhosis)cirrhosis)– Liver failureLiver failure

Hepatitis C already leading cause of liver Hepatitis C already leading cause of liver transplantstransplants

Prevention considerationsPrevention considerations

HIV and hepatitis C have no cures or HIV and hepatitis C have no cures or vaccines vaccines

To prevent transmission, infected persons To prevent transmission, infected persons must reduce partners and likelihood of must reduce partners and likelihood of infecting each partner infecting each partner

Usually requires behavior change; Usually requires behavior change; sometimes, cultural change in an entire sometimes, cultural change in an entire communitycommunity

Many people will change behavior if they know Many people will change behavior if they know they are infected, but both infections may be they are infected, but both infections may be asymptomatic for yearsasymptomatic for years– People may not know they have been exposed, let People may not know they have been exposed, let

alone infectedalone infected

Prevention considerations, Prevention considerations, contd.contd.

Widespread screening and partner Widespread screening and partner notification programs therefore would notification programs therefore would seem to make sense.seem to make sense.

However: However: – Mass screening for hepatitis C has not Mass screening for hepatitis C has not

been funded been funded – Much of the funded screening for HIV is Much of the funded screening for HIV is

anonymousanonymous– Until recently, local health officers have Until recently, local health officers have

not known who is infectednot known who is infected– Insufficient funds or local authority to trace Insufficient funds or local authority to trace

contacts and notify them. contacts and notify them.

The concept of The concept of reproductive rate of a reproductive rate of a disease agentdisease agent

To gradually bring a communicable disease To gradually bring a communicable disease into control, the reproductive rate of the into control, the reproductive rate of the infectious agent (infectious agent (RRoo) must be less than one. ) must be less than one.

RRoo is the number of new cases resulting from is the number of new cases resulting from each case. each case. RRoo == (average transmissions per (average transmissions per exposure) x (exposures/partner) x (partners exposure) x (exposures/partner) x (partners exposed/time) x (length of time patient is exposed/time) x (length of time patient is infectious, lifelong for HIV).infectious, lifelong for HIV).

If this number is greater than one, the If this number is greater than one, the disease will continue to increase disease will continue to increase exponentially.exponentially.

Reproductive rate, contd. Reproductive rate, contd. Ways to reduce RWays to reduce Ro o thereforetherefore include:include:

– Reducing infectiousness of sex or drug abuse, Reducing infectiousness of sex or drug abuse, by using condoms, or clean needles (“harm by using condoms, or clean needles (“harm reduction”)reduction”)

– Eliminating the behavior that causes exposure, Eliminating the behavior that causes exposure, by abstinence, or non-use of injecting drugs by abstinence, or non-use of injecting drugs (exposure prevention, the truest primary (exposure prevention, the truest primary prevention and the topic for another talk)prevention and the topic for another talk)

– Reducing number of persons exposed, by Reducing number of persons exposed, by maintaining only monogamous relationships, or maintaining only monogamous relationships, or non-sharing of needlesnon-sharing of needles

If the average infected person does not If the average infected person does not even know s/he is infected until having even know s/he is infected until having already transmitted the disease, it is already transmitted the disease, it is difficult to explain how difficult to explain how RRoo can be <1 and can be <1 and current prevention strategy can contain current prevention strategy can contain the epidemic.the epidemic.

What else is needed to control What else is needed to control transmission of HIV and transmission of HIV and

hepatitis C?hepatitis C? Communicable diseases are ordinarily Communicable diseases are ordinarily

controlled at the source (the infected controlled at the source (the infected person)person)

Direct work with infected persons Direct work with infected persons (“prevention for positives”) has been (“prevention for positives”) has been missing from prevention programs for missing from prevention programs for both HIV and hepatitis C (and hepatitis both HIV and hepatitis C (and hepatitis B)B)

In the case of HIV, the excuse should In the case of HIV, the excuse should not be lack of money, but for hepatitis not be lack of money, but for hepatitis C, it may beC, it may be

““Prevention for positives”Prevention for positives”

““Prevention case management” can Prevention case management” can assist infected patients to avoid infecting assist infected patients to avoid infecting others.others.

– This can involve encouraging a sense of This can involve encouraging a sense of responsibility not to infect others, and help responsibility not to infect others, and help with techniques for behavior change.with techniques for behavior change.

Partner notification can influence earlier Partner notification can influence earlier reduction in transmission-prone behavior reduction in transmission-prone behavior of persons already infected, and help of persons already infected, and help exposed but not yet infected persons to exposed but not yet infected persons to remain uninfected.remain uninfected.

These services are not routine in most These services are not routine in most parts of California or other places in U.S.parts of California or other places in U.S.

The Uganda Model: “ABC”The Uganda Model: “ABC” A program that seems to have been A program that seems to have been

responsible for reduction of unsafe responsible for reduction of unsafe behavior and HIV prevalence in Uganda is behavior and HIV prevalence in Uganda is known as “ABC.” This has become a known as “ABC.” This has become a centerpiece of the new Global AIDS Bill.centerpiece of the new Global AIDS Bill.

AA = Abstain from sex if possible = Abstain from sex if possible

BB = Be faithful if already involved in a sexual = Be faithful if already involved in a sexual relationshiprelationship

CC = Condoms should be used if A and B are not = Condoms should be used if A and B are not possible.possible.

No current equivalent for needle transmission No current equivalent for needle transmission (most common for hepatitis C)(most common for hepatitis C)

Objectives of Beyond Objectives of Beyond AIDS and allied groupsAIDS and allied groups

Eliminate barriers to applying the most Eliminate barriers to applying the most effective possible prevention techniques for effective possible prevention techniques for HIV. e.g.:HIV. e.g.:– Confidential reporting by name (battle won 2006)Confidential reporting by name (battle won 2006)– Contact tracing, partner notification, and Contact tracing, partner notification, and

prevention case managementprevention case management– Routine and universal screeningRoutine and universal screening– Promotion of cultural changes to avoid exposurePromotion of cultural changes to avoid exposure

Not just depending on reducing the harm caused by Not just depending on reducing the harm caused by exposureexposure

– Devoting resources to diseases in proportion to Devoting resources to diseases in proportion to their importance as public health problemstheir importance as public health problems

Objectives of Beyond Objectives of Beyond AIDS and allied groups, AIDS and allied groups, contd.contd. Eventually, reverse the course of Eventually, reverse the course of

the global HIV pandemic through the global HIV pandemic through sound public health policysound public health policy

Direct attention and resources to Direct attention and resources to other neglected public health other neglected public health priorities, such as hepatitis Cpriorities, such as hepatitis C

Prioritize prevention of transmissionPrioritize prevention of transmission

The non-routine nature of The non-routine nature of HIV testing, 1985-presentHIV testing, 1985-present Anonymous testing offered, on Anonymous testing offered, on

assumption that stigma of HIV will assumption that stigma of HIV will deter confidential testing deter confidential testing

Pre-test counseling encouraged (or Pre-test counseling encouraged (or required for funding), including risks as required for funding), including risks as well as benefits of testingwell as benefits of testing

Unique penalties for unauthorized Unique penalties for unauthorized disclosure of resultsdisclosure of results

Written consent required by most Written consent required by most states under most circumstances states under most circumstances (unlike all other blood tests)(unlike all other blood tests)

The non-routine nature of The non-routine nature of HIV testing, contd.HIV testing, contd. HIV testing is often deferred in medical HIV testing is often deferred in medical

settings due to time and skill settings due to time and skill requirements of counselingrequirements of counseling

HIV Testing has not been included in HIV Testing has not been included in routine panels, including for pregnant routine panels, including for pregnant women in Californiawomen in California

Perception of many patients is that HIV Perception of many patients is that HIV testing is not routine; some may testing is not routine; some may actually be deterred by counseling actually be deterred by counseling

HIV testing: new HIV testing: new technologytechnology

There are now rapid tests, oral and urine tests, There are now rapid tests, oral and urine tests, and home collection kits to mail specimens to and home collection kits to mail specimens to lablab– No home tests to perform yourself…yetNo home tests to perform yourself…yet

November 7, 2002: OraQuick Rapid HIV-1 November 7, 2002: OraQuick Rapid HIV-1 bloodblood test licensed by FDA test licensed by FDA – 20-minute simple fingerstick test20-minute simple fingerstick test– HIV-1/2 version approved March 19, 2004HIV-1/2 version approved March 19, 2004– Approved for clinical laboratoriesApproved for clinical laboratories

Waived CLIA testing approved January 2003 Waived CLIA testing approved January 2003 (apparently for HIV-1(apparently for HIV-1

– Does not include confirmatory testingDoes not include confirmatory testing Can keep specimen for confirmatory Western BlotCan keep specimen for confirmatory Western Blot

HIV testing: new HIV testing: new technology, contd.technology, contd.

March 26, 2004: OraQuick Advance, a Rapid March 26, 2004: OraQuick Advance, a Rapid HIV- 1/2 test approved for HIV- 1/2 test approved for oral mucosal oral mucosal fluidsfluids (not actually saliva) (not actually saliva)– First approved rapid test not requiring bloodFirst approved rapid test not requiring blood

Estimated cost to public health clinics $8/testEstimated cost to public health clinics $8/test http://www.fda.gov/bbs/topics/news/2004/NEW01042.htmlhttp://www.fda.gov/bbs/topics/news/2004/NEW01042.html http://www.medicineonline.com/reference/Health/http://www.medicineonline.com/reference/Health/

Conditions_and_Diseases/Immune_Disorders/Conditions_and_Diseases/Immune_Disorders/Immune_Deficiency/AIDS/info/Rapid-Oral-HIV-Test/Immune_Deficiency/AIDS/info/Rapid-Oral-HIV-Test/

– Oral Western Blot test also approved for Oral Western Blot test also approved for confirmationconfirmation

– CLIA waiver approved June 25, 2004CLIA waiver approved June 25, 2004 http://www.hhs.gov/news/press/2004pres/20040625b.htmlhttp://www.hhs.gov/news/press/2004pres/20040625b.html

– Urine test exists, but not popularUrine test exists, but not popular– Future: Home testing? Pre-date test kits for two?Future: Home testing? Pre-date test kits for two?

HIV testing: new HIV testing: new technology, contd.technology, contd.

What is the difference What is the difference between salivabetween salivaand mucosal transudate?and mucosal transudate?

Oral mucosal transudate Oral mucosal transudate has high concentrations has high concentrations of IgG; saliva has of IgG; saliva has practically none. Oral practically none. Oral mucosal transudate mucosal transudate comes from thecomes from thetissues of the cheek and tissues of the cheek and gum; saliva comes from gum; saliva comes from the salivarythe salivaryglands.glands.

– Information from OraSure Information from OraSure 

The OraSure systemdraws HIV antibodies out of the tissues between the cheek and gum. The virus itself is rarely ever found in oral fluid.

This sample, calledmucosal transudate,contains far fewercontaminants thantypically found insaliva.

HIV testing: new HIV testing: new technology, contd.technology, contd.

http://www.freedomantiviral.com/

HIV testing: new HIV testing: new technology, contd.technology, contd.

HIV testing: signs of HIV testing: signs of changechange Fall 2002: CDC leadership Fall 2002: CDC leadership

expresses increasing concernexpresses increasing concern– Estimated 200 to 250 thousand Estimated 200 to 250 thousand

Americans with HIV do not know Americans with HIV do not know their statustheir status Approximately 25%Approximately 25%

– 40,000 new infections/year40,000 new infections/year Despite over 20 years of prevention Despite over 20 years of prevention

efforts.efforts.

HIV testing: signs of HIV testing: signs of change, contd.change, contd. April 18, 2003 (MMWR): CDC recommends:April 18, 2003 (MMWR): CDC recommends:

– Unlinking HIV counseling from testingUnlinking HIV counseling from testing Both still supported but counseling not a prerequisite Both still supported but counseling not a prerequisite

– Making testing routine in medical and other Making testing routine in medical and other settings.settings.

2003: CDC also informally recommending 2003: CDC also informally recommending “opt-out” prenatal testing“opt-out” prenatal testing– Requires active refusal rather than active Requires active refusal rather than active

written consentwritten consent– Not proposed for other settings at this timeNot proposed for other settings at this time

HIV testing: signs of HIV testing: signs of change, contd.change, contd.

September 22, 2006:September 22, 2006: CDC releases revised CDC releases revised recommendations on HIV testing of adults, recommendations on HIV testing of adults, adolescents, pregnant women in health care adolescents, pregnant women in health care settingssettings– Test routinely in all health care settingsTest routinely in all health care settings

At least annually if high riskAt least annually if high risk– No pre-test prevention counselingNo pre-test prevention counseling– No written consent (the new wrinkle)No written consent (the new wrinkle)

BUT still required by law in CaliforniaBUT still required by law in California ““General consent for medical care” adequate General consent for medical care” adequate BUT also states that patient should be notified first and BUT also states that patient should be notified first and

may refuse (“opt-out” screeningmay refuse (“opt-out” screening– Prenatally, in routine panel (but also “opt-out” Prenatally, in routine panel (but also “opt-out”

screening)screening) Retest in third trimester if high local rate of HIV in Retest in third trimester if high local rate of HIV in

pregnancy pregnancy

Prevention of HIV transmission to Prevention of HIV transmission to babies: “routine & universal” babies: “routine & universal” prenatal testing followed by prenatal testing followed by

medicationmedication 1994: ACTG (AIDS Clinical Trials Group) Protocol 1994: ACTG (AIDS Clinical Trials Group) Protocol

076 study using monotherapy076 study using monotherapy– Zidovudine (AZT) can reduce HIV in babies of infected Zidovudine (AZT) can reduce HIV in babies of infected

women by two-thirdswomen by two-thirds

1998: Institute of Medicine report1998: Institute of Medicine report– Advocates routine and universal prenatal testingAdvocates routine and universal prenatal testing– Notes that counseling can be a barrier Notes that counseling can be a barrier

2001: PACTG (Pediatric AIDS Clinical Trials Group) 2001: PACTG (Pediatric AIDS Clinical Trials Group) Protocol 316Protocol 316– Rate of newborn infection can be reduced from over Rate of newborn infection can be reduced from over

20% to about 1.5% with combination therapy 20% to about 1.5% with combination therapy – More recent studies reduced to near zeroMore recent studies reduced to near zero

The struggle to make prenatal The struggle to make prenatal HIV testing more routine HIV testing more routine

in California (3 Beyond AIDS in California (3 Beyond AIDS bills)bills)

2003: AB 16762003: AB 1676 (John Dutra), similar to two (John Dutra), similar to two previous unsuccessful bills, became lawprevious unsuccessful bills, became law– Pamphlet; simple signature for test Pamphlet; simple signature for test

acceptanceacceptance– Still no “opt-out” testing in California, and Still no “opt-out” testing in California, and

written acceptance neededwritten acceptance needed– Bill will make it easier to combine HIV Bill will make it easier to combine HIV

testing with other routine prenatal teststesting with other routine prenatal tests– Women who miss prenatal testing must be Women who miss prenatal testing must be

asked to accept test during labor/deliveryasked to accept test during labor/delivery

New treatment trends for New treatment trends for HIVHIV

Since 1996, treatment based on “cocktail” of Since 1996, treatment based on “cocktail” of 3 or more drugs, known as HAART (highly 3 or more drugs, known as HAART (highly active anti-retroviral therapy)active anti-retroviral therapy)

A typical regimen A typical regimen – 2 “NRTIs,” (nucleoside or nucleotide reverse 2 “NRTIs,” (nucleoside or nucleotide reverse

transcriptor inhibitors) combined with transcriptor inhibitors) combined with – protease inhibitor or protease inhibitor or – ““NNRTI” (non-nucleoside reverse transcriptase NNRTI” (non-nucleoside reverse transcriptase

inhibitor)inhibitor) Could require multiple pills up to five times a Could require multiple pills up to five times a

dayday

New treatment trends for New treatment trends for HIV, contd.HIV, contd.

Earlier regimens involved complex Earlier regimens involved complex dosages throughout the daydosages throughout the day– Some with food, some without foodSome with food, some without food

Protease inhibitors being combined Protease inhibitors being combined with ritonavir (a member of same with ritonavir (a member of same group) to boost blood levelsgroup) to boost blood levels

Once daily treatment an Once daily treatment an advantageadvantage– Can increase complianceCan increase compliance– MightMight slow development of resistanceslow development of resistance

New treatment trends for New treatment trends for HIV, contd.HIV, contd. Once/day drugs now availableOnce/day drugs now available

– NRTI’s (Nucleoside and nucleotide reverse NRTI’s (Nucleoside and nucleotide reverse transcriptase inhibitors):transcriptase inhibitors):

Videx EC (didanosine/ddI, long-acting capsule)Videx EC (didanosine/ddI, long-acting capsule) Epivir (lamivudine/3TC)Epivir (lamivudine/3TC) Emtriva (emtricitabine, similar to lamivudine)Emtriva (emtricitabine, similar to lamivudine) Viread (tenofovir)Viread (tenofovir)

– NNRTI (Non-nucleoside reverse NNRTI (Non-nucleoside reverse transcriptase inhibitor):transcriptase inhibitor):

Sustiva (efavirenz)Sustiva (efavirenz)

– PI (Protease inhibitor):PI (Protease inhibitor): Reyataz (atazanavir)Reyataz (atazanavir)

New treatment trends for New treatment trends for HIV, contd.HIV, contd. Combination pillsCombination pills

– Reduce resistance due to noncomplianceReduce resistance due to noncompliance Strategy previously utilized for TBStrategy previously utilized for TB

– One pill twice/day combo pillsOne pill twice/day combo pills Combivir (zidovudine + lamivudine)Combivir (zidovudine + lamivudine) Trizivir (zidovudine + lamivudine + abacavir)Trizivir (zidovudine + lamivudine + abacavir)

– One pill once/day combo pillsOne pill once/day combo pills Epzicom (abacavir + lamivudine)Epzicom (abacavir + lamivudine) Truvada (emtricitabine + tenofovir)Truvada (emtricitabine + tenofovir) Atripla (emtricitabine + tenofovir + Atripla (emtricitabine + tenofovir +

efavirenz)efavirenz)

New treatment trends for New treatment trends for HIV, contd.HIV, contd. An earlier concept was to “hit early, hit An earlier concept was to “hit early, hit

hard” with the combination of drugshard” with the combination of drugs Now, onset of treatment is delayed till Now, onset of treatment is delayed till

CD4 count is decreasing (e.g., <350)CD4 count is decreasing (e.g., <350)– This change due to high rate of side effects and This change due to high rate of side effects and

diminished effectiveness if used for many yearsdiminished effectiveness if used for many years

– May take years of infection before current May take years of infection before current treatment criteria are mettreatment criteria are met

Early treatment to reduce infectiousness can no longer Early treatment to reduce infectiousness can no longer be proposed as a major control strategybe proposed as a major control strategy

– What is good for the patient may not always be What is good for the patient may not always be what is good for public healthwhat is good for public health

New treatment trends for New treatment trends for HIV, contd.HIV, contd. With increasing drug resistance, With increasing drug resistance,

especially among patients treated especially among patients treated for many years, HIV is becoming for many years, HIV is becoming more difficult to treat with existing more difficult to treat with existing drugs.drugs.

First fusion inhibitor, Fuzeon became First fusion inhibitor, Fuzeon became available 2003 but requires 2 available 2003 but requires 2 injections/day and costs $20,000/yr.injections/day and costs $20,000/yr.

Treatment trends for Treatment trends for hepatitis Chepatitis C

Former Treatment of hepatitis CFormer Treatment of hepatitis C– Short-acting interferons requiring 3 times a Short-acting interferons requiring 3 times a

week (TIW) shotsweek (TIW) shots– Oral ribavirin daily (sold together in Oral ribavirin daily (sold together in

RebetronRebetron®®)) Interferon Interferon alpha-2aalpha-2a (Roferon-A®): 3 MU TIW (Roferon-A®): 3 MU TIW

Interferon Interferon alpha-2balpha-2b (Intron-A®) 3 MU TIW (Intron-A®) 3 MU TIW

Alfacon-1 (Infergen®):Alfacon-1 (Infergen®): 9 9 g TIWg TIW

IFN alpha-2b + Ribavirin (Rebetron®)IFN alpha-2b + Ribavirin (Rebetron®)

3 MU TIW3 MU TIW Pt weight Pt weight ≤ ≤ 75kg: 1000mg75kg: 1000mg

Pt weight > 75kg: 1200mgPt weight > 75kg: 1200mg

Current treatment: longer acting Current treatment: longer acting “pegylated” interferons, weekly “pegylated” interferons, weekly

shotsshots Only the interferon has changedOnly the interferon has changed

– Now long-acting, inject only once/weekNow long-acting, inject only once/week– Still accompany with daily oral ribavirinStill accompany with daily oral ribavirin

First product:First product:– 12 kD12 kD Peginterferon alpha 2b (PegIntron®) 1.5 Peginterferon alpha 2b (PegIntron®) 1.5

mg/kg injection + Ribavirin 800 mg/day orallymg/kg injection + Ribavirin 800 mg/day orally– Regimen that received FDA approval– Higher Ribavirin doses NOT prospectively

studied nor FDA approved

Current treatment for hepatitis C, Current treatment for hepatitis C, contd. – latest product contd. – latest product pairpair

40 kD40 kD Peginterferon alpha 2a Peginterferon alpha 2a (Pegasys®) (Pegasys®)

– 180 mcg sq weekly180 mcg sq weekly

+ Ribavirin (Copegus®)+ Ribavirin (Copegus®)≤≤ 75kg, 1000mg/d75kg, 1000mg/d

>75 kg, 1200mg/d>75 kg, 1200mg/d

Treatment problemsTreatment problems

All current treatments for both HIV All current treatments for both HIV and hepatitis C are very expensive and hepatitis C are very expensive and have significant toxicityand have significant toxicity

– Antiretroviral drugs cause GI side effects, Antiretroviral drugs cause GI side effects, anemia, rash, fat redistribution anemia, rash, fat redistribution (lipodystrophy), pancreatitis, neuropathy, (lipodystrophy), pancreatitis, neuropathy, hyperlipidemia, even diabetes hyperlipidemia, even diabetes

Sometimes hard to tell which drug is responsible, Sometimes hard to tell which drug is responsible, because used together and HIV alone can cause because used together and HIV alone can cause some of these effectssome of these effects

– Interferon causes flu-like symptoms, Interferon causes flu-like symptoms, neutropenia, thyroid problems, depression, neutropenia, thyroid problems, depression, even suicide; ribavirin causes hemolytic even suicide; ribavirin causes hemolytic anemia and birth defects requiring anemia and birth defects requiring 2 2 methodsmethods of contraception of contraception

Treatment problems, Treatment problems, contd.contd. Drugs are needed that are active Drugs are needed that are active

against against bothboth HIV and hepatitis C HIV and hepatitis C

– Lamivudine and tenofovir are active Lamivudine and tenofovir are active against both HIV and hepatitis B (so against both HIV and hepatitis B (so is adefovir, though withdrawn for is adefovir, though withdrawn for HIV), but no drugs currently help HIV), but no drugs currently help both HIV and hepatitis C.both HIV and hepatitis C.

Initiatives by private industryInitiatives by private industry

In Africa, pharmaceutical companies In Africa, pharmaceutical companies (stung by criticism for high drug costs) (stung by criticism for high drug costs) collaborating with NGOs (non-collaborating with NGOs (non-governmental organizations) to fund governmental organizations) to fund programs for treatmentprograms for treatment

Pharmaceutical companies reducing prices Pharmaceutical companies reducing prices on drugs for third worldon drugs for third world– Waiving patents to permit local manufacture of Waiving patents to permit local manufacture of

genericsgenerics

In absence of adequate funding for In absence of adequate funding for hepatitis C prevention, pharmaceutical hepatitis C prevention, pharmaceutical companies (e.g., Schering, Roche) a key companies (e.g., Schering, Roche) a key source of educational materialssource of educational materials

Conclusions:Conclusions:

HIV and hepatitis C are both difficult to HIV and hepatitis C are both difficult to control and difficult to treatcontrol and difficult to treat– Neither is curable and neither has a vaccineNeither is curable and neither has a vaccine– Both are immense public health problems.Both are immense public health problems.

Public health efforts are hampered byPublic health efforts are hampered by– Political restrictions (especially for HIV)Political restrictions (especially for HIV)– Lack of funding (especially for hepatitis C)Lack of funding (especially for hepatitis C)

New strategic approaches and new New strategic approaches and new treatment strategies have recently been treatment strategies have recently been developed; longterm results are unknowndeveloped; longterm results are unknown

Continued creative approaches are Continued creative approaches are neededneeded