substance abuse & hiv disease janet l. mitchell, m.d., m.p.h., f.a.c.o.g. consultant on...
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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
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
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 & 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.
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
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
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