SUBSTANCE ABUSE&

HIV DISEASEJanet L. Mitchell, M.D., M.P.H., F.A.C.O.G.

Consultant on Women’s Health

Addiction, Research & Treatment Corporation

Brooklyn, NY

• Epidemiology

• HIV care

EPIDEMIOLOGY

Age at Diagnosis

AIDS Cases by Age and SexReported 1981-1999, United States

Nu

mb

er

of

Case

s

0 10 20 30 40 50 60 70 80 90

Female N=124,045Male N=609,326

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

AIDS Cases in Adult/Adolescent Men, Reported

July 1998 - June 1999, and Estimated AIDS incidence,* Diagnosed July 1998 – June 1999 by Risk Exposure United States

* Data adjusted for reporting delays and estimated proportional redistribution of cases initially reported withoutrisk. Data reported through March 2000.

AIDS Incidence Reported July 1998 - June 1999

Estimated AIDS Incidence*Diagnosed July 1998 - June 1999

<1%<1%1%

<1%<1%

45%

21% 21%

5% 8%

53%

13%27%

6%

Risk Exposure

Injection drug use (IDU)

Men who have sex with men

Hemophilia

Transfusion

Heterosexual contact

MSM/IDU

Other/not identified

36%

62%

28%

31%

40%

AIDS Incidence Reported July 1998 - June 1999

Estimated AIDS Incidence*Diagnosed July 1998 - June 1999

2%<1%1%

<1%1%

Injection drug use (IDU)

Hemophilia

Transfusion

Heterosexual contact

Other/not identified

Risk Exposure

* Data adjusted for reporting delays and estimated proportional redistribution of cases initially reported withoutrisk. Data reported through March 2000.

AIDS Cases in Adult/Adolescent Women, Reported July 1998 - June 1999, and Estimated AIDS Incidence,*

Diagnosed July 1998 - June 1999, by Risk Exposure United States

1 9 8 6 1 9 8 8 1 9 9 0 1 9 9 2 1 9 9 4 1 9 9 6 1 9 9 8 2 0 0 0

0

10

20

30

40

50

60

70

Year of Report

Perc

ent o

f Cas

es

American Indian/Alaska Native

Black, not Hispanic

Hispanic

Asian/Pacific Islander

White, not Hispanic

Proportion of AIDS Cases, by Race/Ethnicity and Year of Report,1985 - 2000, United States

AIDS in Blacks and Hispanics

Of the 774,467 AIDS cases reported to CDCthrough 2000, Blacks and Hispanics accounted for

Of AIDS cases reported in 2000, 66% were among Black and Hispanic adults and adolescents.

*Heterosexual injection drug users and persons with heterosexually acquired HIV

56% of total78% of women79% of heterosexuals*82% of children

and Race/Ethnicity, Reported through 2000, United StatesAIDS Cases in Adults and Adolescents by Exposure Category

*Includes patients with hemophilia or transfusion-related exposures and those whose medical record review is pending; patients who died, were lost to follow-up, or declined interview; and those with other or undetermined modes of exposure

not Hispanic not Hispanic White

N umber % N umber % N umber %

68

12

8

5

Black

27

36

6

16

Hispanic

35

36

5

13

223,470

39,764

24,958

16,866

78,651

102,492

15,848

45,601

48,287

50,196

7,673

18,683

7 16 1124,551 44,699 14,823

Exposure category

Men who have sex with men (MSM)

Injection drug use (IDU)

Heterosexual contact

Total

MSM and IDU

O ther/ not identified*

329,609 287,291 139,662

HIV CARE

“Women should be treated for their disease first.”

Age at Diagnosis

AIDS Cases by Age and SexReported 1981-1999, United

States

Nu

mb

er

of

Case

s

0 10 20 30 40 50 60 70 80 90

Female N=124,045Male N=609,326

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

05

10152025303540455055

82 84 86 88 90 92 94 96 98*

Year

Dea

ths p

er 1

00,0

00 P

opul

atio

n

Cancer

Heart disease

HIV infection

UnintentionalinjuryHomicide

Stroke

Diabetes

Liver disease

Suicide*Preliminary 1998 data

Trends in Annual Rates of Death from Leading Causes of DeathAmong Black Women 25-44 Years Old, USA, 1982-1998

National Center for Health StatisticsNational Vital Statistics System

0

10

20

30

40

50

60

70

80

90

87 88 89 90 91 92 93 94 95 96 97

Year

Perc

ent

Male

Female

Trends in the Percentage Distribution of Deaths from HIV Infection, By Sex, USA, 1987-1997

National Center for Health StatisticsNational Vital Statistics System

0

10

20

30

40

50

60

70

87 88 89 90 91 92 93 94 95 96 97

Year

Perc

ent

Black

White

Other*

Trends in the Percentage Distribution of Deaths from HIV Infection, By Race, USA, 1987-1997

*Asian, Pacific islander, or American IndianNational Center for Health StatisticsNational Vital Statistics System

0

10

20

30

40

50

60

70

80

90

Northeast South West MidwestRegion

Dea

ths

per 1

00,0

00 P

opul

atio

n

Non-HispanicBlack

Hispanic

Non-HispanicWhite

American Indianor Alaska Native

Asian or PacificIslander

*Adjusted to the age distribution of the projected year 2000 U.S. population

Age-adjusted* Mean Rate of Death from HIV Infection during 1993-1997,By Race / Ethnicity and Geographic Region, USA

National Center for Health Statistics, National Vital Statistics System

Is the Disease Different?• Diagnosis

– Presenting complaints– Presenting diagnosis

• Presentation– Heterosexual – Over 50 age group

• Treatment response– CD4/Viral load– Response to therapies

HIV Care

• Anti-retrovirals

• Prophylaxis

• Co-morbid conditions

HIV Care & Women’s Health

• Pre-conceptual Counseling– Pregnancy Planning?

• Anti-retrovirals– Efavirenz?

• Prophylaxis

• Co-morbid conditions– Diabetes– HTN

Phase Tmax (h) Cmax (nM) AUC (nM•h)Menstrual 1.25 (0.5-1.5) 8690 (5400-

12500)20200 (8900-

37700)Follicular 0.5 (0.5-1.0) 15400 (5950-

19800)34000 (6460-

46500)Luteal 2.0 (1.0-3.0) 8840 (3850-

14400)27600 (12100-

35900)

Pharmacokinetic of Indinivir in Menstruating Women

n=6

(age 37±5.4 years, CD4 count 354±137 cells/mm3)

ANTI-RETROVIRALS

EFFECTS ONMETHADONE

PRESUMED MECH. OFACTION

DATA

Nevirapine Reduced Induction of CYP-450 Clinical &limited PK

Efavirenz Reduced Induction of CYP-450 ClinicalRitonavir Increased Inhibition of CYP-450 Clinical &

limited PKNelfinavir Reduced ?? Induction of CYP-450 Clinical &

PKLopinavir/ritonavir

Reduced ?? Induction of CYP-450 Clinical &PK

Zidovudine ReducedZidovudine*

Inhibition of intracellularphosphorylation

Limitedclinical & PK

Didanosine ReducedDidanosine*

Inhibition of intracellularphosphorylation

Limitedclinical & PK

CYP-450: cytochrome P-450; PK: pharmacokinetics*No alteration in the pharmacokinetics of methadone, but aninteraction with the intracellular pharmacokinetics of the nucleosideanalogue.

Interactions Between ARV and Ethinyl Estradiol

Do not use Levels EERitonavir

Usual dosesNo interactionAmprenavir

Do not use Levels EENelfinavir

Usual dosesNo interactionIndinavir

Usual doses EE AUC 37%Efavirenz

Do not use EE AUC 19%Nevirapine

RecommendationEffect on EEARV

ANTIRETROVIRALS EFFECTS ONMETHADONE

PRESUMED MECH.OF ACTION

DATA

Nevirapine Reduced Induction of CYP-450 Clinical &limited PK

Efavirenz Reduced Induction of CYP-450 ClinicalRitonavir Increased Inhibition of CYP-450 Clinical &

limited PKNelfinavir Reduced ?? Induction of CYP-

450Clinical &PK

Lopinavir/ritonavir Reduced ?? Induction of CYP-450

Clinical &PK

Zidovudine ReducedZidovudine*

Inhibition ofintracellularphosphorylation

Limitedclinical & PK

Didanosine ReducedDidanosine*

Inhibition ofintracellularphosphorylation

Limitedclinical & PK

CYP-450: cytochrome P-450; PK: pharmacokinetics*No alteration in the pharmacokinetics of methadone, but an interactionwith the intracellular pharmacokinetics of the nucleoside analogues.

“Lipodystrophy”

What does it mean?

HIV-Associated Lipodystrophy

Fat Fat atrophyatrophy

Fat Fat accumulationaccumulation

HyperlipidemiaHyperlipidemia Insulin resistanceInsulin resistance

Aims: Guidelines

• Glucose metabolism

• Lipid metabolism

• Body composition

• Cardiovascular risk

• Lactic acidemia

• Osteopenia

Lipid Control Contrast of PI Reported Data

HDLHDL

Activella ™Activella ™1mgE/.5mg 1mgE/.5mg

NETANETA

Prempro®Prempro®.625mgE/2.5.625mgE/2.5

mg MPAmg MPA

3.53.5

FemHRT ™FemHRT ™5mcgE/1mg5mcgE/1mgNETANETA

-6.7-6.7

Ortho-Prefest™Ortho-Prefest™1mgE/.091mgE/.09mg NGMmg NGM

9.79.7

TriglyceridesTriglycerides

Lipid Profile(mean % change from baseline after 1 year of treatment)

9.49.4

-12.4-12.4

2.22.2 24.124.1 12.112.1

LDLLDL -4.9-4.9 -7.5-7.5-8.8-8.8-10.8-10.8

OBSTETRICAL CARE

Pregnancy

• Pregnancy does not accelerate HIV disease

• Stage of HIV disease can impact pregnancy outcome

• Perinatal transmission rates depend on multiple factors

• The use of anti- retrovirals for the treatment of the woman’s disease transmission rates > than elective c/sections

Current Standard of Care for Pregnant Women in Developed Countries

Combination Anti-retroviral Therapy (should include AZT if appropriate)

Perinatal Transmission Rates

• Zidovudine/ ACTG 076

• Combination therapy/HAART

• Nevirapine

• Elective c/section

Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy

www.hivatis.org/guidelines/adult/text/pregnancy1.html

Antiretroviral Pregnancy Registry

1410 Commonwealth Drive

Wilmington, NC 28403

telephone (800) 258-4263

fax (800) 800-1052

CDC WEBSITE:

http://www.cdc.gov/hiv/graphics.htm