Download Women, Pregnancy and PMTCT

Women: HIV, ART and
PMTCT
HIV Care and ART:
A Course for Pharmacists
Introductory Case: Alem
 A 32 year-old woman returns to the pharmacy
one month after starting ART. As she reaches for
her prescriptions, you notice that she is
scratching her arms. You know that many ART
medications can cause a rash, so you look to
see what she is taking
 Her regimen is as follows: Nevirapine 200 mg
bid, lamivudine 150 mg bid and stavudine 40 mg
bid
 You see a rash on her arms that is blistering.
She does not look well
2
Introductory Case: Alem (cont.)
Which of the following statements is true about nevirapine
and the potential for side effects in women?
1. There are no differences between men and women in
regard to nevirapine side effects
2. Women are equally at risk as men for developing
hepatitis from nevirapine
3. Women have a higher risk for developing severe (grade
3 or 4) skin rashes than men
4. Women are at greater risk of developing lactic acidosis
from nevirapine than men
3
Learning Objectives
 Part 1: Women and HIV
 Explain the epidemiology of HIV disease in women
 Recognize the gender differences regarding ART
between men and women
 Identify significant toxicities of antiretroviral therapy
that are more common in women than men
4
Learning Objectives
 Part 2: Pregnancy, ART and PMTCT
 Identify risk factors for maternal to child transmission
and ways to reduce risk
 Identify ARV drugs that can be used during pregnancy
to prevent MTCT
 Recognize indications for ART and first line regimens
in pregnancy
 Understand the safety and efficacy of ARVs during
pregnancy
5
Part 1: Women and HIV
Global Facts
 Of 40 million people living with HIV/AIDS
worldwide, 17.5 are women (2005)
 77% of all women living with HIV are in subSaharan Africa (2005)
 Among HIV positive adults, women account for
57% in sub-Saharan Africa, 26% in southeast
Asia, 27% in Europe, and 25% in the US (2005)
7
UNAIDS Estimates for Ethiopia
 There were 1.9 million HIV-positive adults, over
half of whom (1.1 million, 57.9%) were women,
(1.5, 770K women, 2003)
 The group with the highest prevalence in the
country is women ages 15-24
 Decline in HIV prevalence has been detected among
young inner-city women in Addis Ababa; infection
levels among women 15–24 attending antenatal
clinics dropped from 24.2% in 1995 to 15.1% in 2001
8
Prevalence of HIV in Young
Women (Sub-Saharan Africa)
9
Source: UNAIDS Report on the Global AIDS Epidemic 2004
Vulnerability Factors




Biological
Economic
Social
Cultural
“Women are most vulnerable to HIV infection,
given the social and economic disadvantages
they face in their day to day lives.”
• Dr. Nafis Sadik, Executive Director of the
United Nations Population Fund
10
Gender Differences








Viral load
Disease progression
Drug pharmacokinetics
Lipodystrophy
Lactic acidosis
Contraceptives
Adherence
Gynecological Issues
11
Viral Load and
Disease Progression
 Women may have lower viral loads than men in
early disease
 Low viral load may NOT truly reflect low risk for
progression
 Women and men progress at similar rates
 Gender not significantly associated with time to
AIDS or survival time
12
Drug Pharmacokinetics
 Body size—differences in weight
 Fat to muscle distribution
 Concentration of enzymes needed for drug
metabolism is different
 Hormonal effects
 Pregnancy
 Hormonal replacement therapy
 Oral contraceptives
13
Lipodystrophy
 Fat accumulation more common in women; fat
depletion more common in men
 Accumulation and depletion in different body
areas of same person occurs equally in men and
women
 Lipid abnormalities: triglyceride and cholesterol
level elevations more common in men
14
Lactic Acidosis
 The FDA has received 60 reports of lactic
acidosis associated with dual nucleosides, with
55% mortality
 83% in women; 50% >175lbs
 Presented with nonspecific symptoms
 Link between mitochondrial dysfunction and
lactic acidosis?
 Occurs in women with high CD4
15
Contraception and ART
 Efavirenz is contraindicated in pregnancy
 Additional barrier methods are recommended to
prevent pregnancy and transmission of HIV and
STIs
 Dual methods of contraception highly
recommended for sexually active EFV users:
barriers plus:
 Progestins (Depo-Provera)
 IUCD
16
Antiretrovirals and Oral Contraceptives
 NNRTIs and PIs interfere with blood levels of
combination oral contraceptives
 Nelfinavir, Nevirapine and Ritonavir
 Associated with decreased levels of ethinyl estradiol,
resulting in decreased contraceptive effectiveness
 Do not combine
17
Drug Interactions
 Hormonal contraception
 Nevirapine, lopinavir, ritonavir, and nelfinavir may lead
to sub therapeutic levels of ethinyl estradiol (EE)
resulting in unwanted pregnancy
 Atazanavir, efavirenz, & indinavir increase
EE/norethindrone
 Must use additional/alternate method of contraception
18
Women and Adherence
 Adherence issues are more complicated for
women who need special attention and support:




Often don’t disclose HIV status due to stigma
May feel isolated
Caregivers
Challenges in accessing and maintaining care include
child care, transportation, inexperienced providers,
etc.
19
Optimal Adherence for Women
 Evaluate for mental health, substance abuse
and other “adherence interruptus” problems
 Assess HAART readiness
 Develop a mutually agreeable HAART regimen
specific to her lifestyle
 Prepare for side effects
 Encourage atmosphere of communication and
trust
 Be accessible and available
20
Gynecological Issues
 Conditions causing inflammation or infection increase
the likelihood a woman will acquire or transmit HIV





Bacterial vaginosis
Cervicitis
Herpes ulcers
Genital warts
Condyloma
 Recurrent candidiasis
 Prevalent in 25-30% of women with HIV
 Risk increases 20-fold with CD4<100
 HPV genital warts associated with increased incidence
of cervical cancer
21
ARV Drugs Toxicity in Women:
How Do They Differ From Men?








Rash
Hepatotoxicity
Lactic acidosis/Hepatic steatosis
Mitochondrial toxicity
Dysmenorrhea
Lipodystrophy/Hyperlipidemia
Osteoporosis
Renal compromise
22
ARV Drugs Toxicity in Women: NNRTIs
 Nevirapine (NVP)
 Rash
• Females 5.5 to 7.3 x more likely to develop NVP
associated severe skin rash than men
 Hepatotoxicity
• Females up to 3 x more likely than men
• When CD4 count is >250 there is a much higher risk
 Time to onset:
• Risk of rash or heatotoxicity greatest in the first 4-6
weeks of therapy
• NVP first 18 weeks: requires close monitoring
23
Introductory Case: Alem (cont.)
1. There are no differences between men and
women in regard to nevirapine side effects
FALSE


Women are at greater risk of developing both rash
and hepatotoxicity from nevirapine than men
Women who begin nevirapine should be monitored
closely for the first 6 weeks (up to 18 weeks) on
therapy
24
Introductory Case: Alem (cont.)
2. Women are equally at risk as men for
developing hepatitis from nevirapine
FALSE
 Overall (men and women combined) incidence of
symptomatic hepatotoxicity is 4%, asymptomatic
hepatitis: 8.8%
 Hepatotoxicity generally occurs within first 4-6
weeks of therapy
25
ARV Drugs Toxicity in Women: NNRTIs (2)
 Efavirenz
 Rash:
• 26% of patients experience, <2% requiring
discontinuation
• Female sex an independent risk factor
 Teratogenic: causes birth defects
• should be avoided in pregnancy
• should be avoided in women of childbearing age
• should only be used in women of childbearing age if
effective contraception is absolutely in place
26
Introductory Case: Alem (cont.)
3. Women have a higher risk for developing severe
(grade 3 or 4) skin rashes than men
TRUE

Overall (men and women combined) the incidence of rash is 15%
• Women are as much as 8x more likely than men to develop
rash
• Rash generally occurs in the first 6 weeks of therapy
• Female sex is an independent risk factor
27
ARV Drugs Toxicity in Women: NRTI’s
 Mitochondrial toxicity: class effect greater in
women
 Attributed to higher intracellular drug levels
 Lactic acidosis and hepatic steatosis




Symptoms are vague
May be associated with pancreatitis
Other risk factors: obesity and prolonged use of NRTIs
DDI + D4T combination is added risk
• Must avoid use in pregnancy
28
Introductory Case: Alem (cont.)
4. Women are at greater risk of developing lactic
acidosis from nevirapine than men
FALSE
 Women are at greater risk of developing lactic
acidosis. It is most likely caused by nucleoside
analogues
 Nevirapine has not been shown to cause lactic
acidosis
29
ARV Drugs Toxicity in Women: PI’s
 Hyperglycemia**
 PI use, age and Body Mass Index (BMI) are
independent predictors of developing diabetes
 Routine screening for diabetes is essential among
patients on PI therapy
 Drug interactions
 Oral contraceptives
 Hormonal replacement therapy
 Effect of menstrual cycle
 Drug serum levels
30
ARV Drugs Toxicity in Women: PI’s (2)
 Lipodystrophy
 Recent evidence suggests that levels of body fat
change are comparable among men and women
• Lipoatrophy (fat loss) is the predominant body shape
change in women
 Lipid abnormalities
• Elevation of triglycerides and cholesterol (much more
common in men)
31
ARV Drugs Toxicity in Women:
All ARVs
 Renal toxicity
 Limited information
 Decreased bone mineral density
 3 studies found that traditional risk factors and not
ARVs were associated with decreased bone mineral
density (BMD)
• CROI 2003 (Abstract 102,103,766)
32
Treatment Guidelines for Women
 Guidelines are not gender specific
 Issues to consider when starting treatment
 Preconception counseling
• Teratogenicity of ARVs




Drug interactions
Efficacy
Tolerability, side effects
Co-morbidities (TB, pregnancy, depression)
33
Women of Reproductive Age
 Regimen selection should account for the possibility of
planned or unplanned pregnancy
 Sexual activity, reproductive plans and use of effective
contraception, should be discussed with the patients
 When evaluating for initiation of therapy, counsel on the
potential risk of efavirenz containing regimen
 Avoid efavirenz
• in pregnancy
• If woman is not using consistent contraception
34
Part 2:
HIV, Pregnancy and Preventing
Maternal to Child Transmission
Introduction
 HIV is a family infection
 Mothers and fathers have an impact on
transmission of HIV to the baby
 There is increased chance of transmission to the
baby when a woman becomes infected with HIV
when she is pregnant or breastfeeding
 Partners should have safer sex throughout
pregnancy and while breastfeeding
36
Pregnant Women Testing HIV Positive
2001, Ethiopia, Urban
Shashemene
13.1
Gambella
14.6
Gonder
15.1
Dire dawa
15.2
Addisava
15.6
Adigrat
16.2
Maichew
16.8
MKELIE
17.2
Nazareth
18.7
Jijiga
19
Bahrdar
23.3
0
5
10
15
20
25
Prevalence (%)
Source: AIDS in Ethiopia, 4th Edition, October 2002. CDC/MOH
37
Pregnant Women Testing HIV
Positive 2001, Ethiopia, Rural
Attat
1.5
Gambo
1.1
Aira
2.6
Borena Dadim
1.7
BOREA Gosa
1.7
Ambo Toke
4.6
0
1
2
3
4
5
Prevalence (%)
Source: AIDS in Ethiopia, 4th Edition, October 2002. CDC/MOH
38
Pregnancy Outcome: Goals
 Uncomplicated pregnancy
 Healthy, uninfected infant
 Healthy mother who has not compromised her
future options for HIV therapy
39
HIV and Pregnancy
 Pregnancy does not
accelerate the
progression of HIV
disease to AIDS
 Patients with AIDS are
more likely to suffer from
pregnancy-related
complications
40
Effect of Advanced HIV on Pregnancy
 Decreased fertility
 Spontaneous abortion
 Infections (opportunistic, GU, postpartum, postsurgical)
 Preterm labor
 Premature rupture of membranes
 Low birth weight babies
 Stillbirths
41
Current Status of
Mother-to-Child Transmission
 Estimates of HIV transmission rates from women
to children are about 20-40%
 MTCT is by far the largest source of HIV
infection in children under 15
42
Estimated risk and timing of MTCT in
the absence of interventions
Timing
Transmission Rate
During pregnancy
5-10%
During labour and delivery
10-15%
During breastfeeding
5-20%
Overall without breastfeeding
15-25%
Overall with breastfeeding to six months
20-35%
Overall with breastfeeding to 18-24 months
30-45%
Note: Rates vary because of differences in population characteristics such as
maternal CD4+ cell counts, RNA viral load and duration of breastfeeding
Source: World Health Organization. HIV transmission through
breastfeeding. A review of available evidence.
43
Factors Influencing MTCT
 Viral Load
 The higher the viral load, the higher the risk of MTCT
 Lowering risk through:
 Use of ART during pregnancy and postpartum to
mother and newborn
 Adequate nutrition, particularly vitamin A
44
Factors Influencing MTCT (2)
 Maternal Factors Increasing Risk
 Viral or parasitic placental infection (especially
malaria)
 Becoming infected with HIV during pregnancy
 Severe immune deficiency
 Advanced clinical and immunological state
 Maternal malnutrition
45
Factors Influencing MTCT (3)
 Labor and Delivery—Factors Increasing Risk









Prolonged rupture of membranes (>4 hours)
Injury to birth canal during child birth
Antepartum procedures
Acute chorioamnionitis
Invasive fetal monitoring
Instrumental delivery
Mixing of maternal and fetal body fluids
Delayed infant cleaning and eye care
Routine infant airway suctioning
46
Factors Influencing MTCT (4)
 Fetal Conditions





Premature delivery
Low birth weight
Immature immune status
First infant in a multiple birth
Oral diseases
47
ART Clinical Scenarios
 Four possible clinical scenarios of a pregnant
woman:




On ART and become pregnant
Pregnant and ART indicated and available
Pregnant and not requiring ART or ART not available
Pregnant and presenting after 34 weeks with no prior
ART
48
Scenario 1:
On ART and Become Pregnant
 Woman on efavirenz
 Counsel about potential
teratogenicity
 Stop EFV and start NVP if
in first trimester
 Woman on
D4T/3TC/nevirapine
 Woman on
ZDV/DDI/LPV/r
 Continue treatment
 Full blood count monthly
 Monitor blood glucose
levels as appropriate
 Continue treatment or
change D4T to ZDV (full
blood count monthly if on
ZDV)
 ALT monthly & when
indicated
49
Scenario 2:
Pregnant and Eligible for ART
 Begin first line therapy for woman:
 ZDV 300 mg bid or D4T 40 mg every 12 hours (or 30 mg q 12
hours if <60 kg)

+
 3TC 150 mg q12 hrs

+
 NVP 200 mg qd for 2 weeks, then 200 mg q12 hrs
 If unable to use NVP, PI options include NFV, LPV/r or SQV/r
 ALT q 2 weeks for 1 month, then q month, then as indicated
 Begin AZT 4 mg/kg for 7 days for infant
50
Scenario 3:
Pregnant and Not Requiring ART
 Early stage HIV (WHO Stage I or II disease with
CD4 >200)
 Follow the national PMTCT guidelines
51
Scenario 4:
Pregnant Presenting After 34 Weeks
 Defer ART
 Provide PMTCT
 Review need for ART after delivery
52
Use of Antiretrovirals in Pregnancy:
Potentially Competing Issues
Safety &
Efficacy for
Mother
Safety
of
Infant
Prevention
of
Transmission
53
Antiretroviral Therapy to
Reduce Perinatal Transmission: Options
 Short course ARV prophylaxis for PMTCT
 HAART not available or indicated
 HIV+ woman presents in labor with no prior ARV
 Capacity for ARV prophylaxis limited to Nevirapine to
mother and infant
54
Short course ARV Prophylaxis for
PMTCT* - Scenario #1
Maternal
antepartum
Maternal
intrapartum
Maternal
postpartum
Infant
NVP 2
mg/kg
AZT 300 mg
single dose
bid orally
AZT 300 mg
HAART not
with 72
starting at
Single dose and 3TC
available or
hours of
28 weeks
NVP 200
150 mg
not
birth AND
pregnancy
mg orally
orally BID 7
indicated
AZT 4
or as soon
days
mg/kg orally
as possible
bid for 7
days
55
Short course ARV Prophylaxis for
PMTCT* - Scenario #2
Maternal
antepartum
HIV +
woman
presents
in labor
with no
prior ARV
Maternal
intrapartum
Single dose
NVP 200
mg orally
AND AZT
300 mg
orally every
12 hours
until delivery
Maternal
postpartum
Infant
If mother received
NVP less than 2
hours before
delivery, infant
should be given
TWO doses of NVP
2 mg/kg orally
-ONCE as soon as
possible after
delivery
-SECOND dose at
48-72 hours of life
56
Short course ARV Prophylaxis for
PMTCT* - Scenario #3
Capacity
for ARV
prophylaxi
s limited to
Nevirapine
for mother
and infant
Maternal
Maternal
Maternal
antepartum intrapartum postpartum
Infant
Single
dose NVP
200 mg
orally
NVP 2
mg/kg
orally
within 72
hours of
birth
57
WHO Recommendations
 For mothers presenting in labor without prior ART,
 Single dose nevirapine and zidovudine given to the mother
during labor
 And, single dose nevirapine and four weeks of zidovudine from
birth given to the infant
 Or
 Zidovudine/lamivudine during delivery and for 7 days postpartum
given to the mother
 And, Zidovudine/lamivudine for 7 days given to the infant from
birth
 Where capacity to deliver only minimal range of ARVs
exists:
 Single dose nevirapine for the mother during labor
 And, single dose nevirapine for the infant within 72 hours of birth
Source: WHO, Antiretroviral drugs and prevention of mother-to-child transmission of
HIV infection in resource-limited settings: Recommendations for a public health 58
approach (2005 Revision).
Single Dose Nevirapine: ART
Prophylaxis for PMTCT
 Advantages:






Rapid oral absorption
Rapid transplacental passage
Highly potent antiviral
Long half-life, persists for 7-10 days
NVP provides prophylaxis to the baby during birth
Toxicities rare: severe rash, hepatitis
 Disadvantage:
 Rapidly selects for drug-resistant mutants
59
MTCT: Single-Dose
Nevirapine Vs Ultra-Short ZDV
% Transmission
Breastfed Infants
14-16 weeks 18 months
Nevirapine INTRA POST
versus
13.1%
15.7%
25.1%
25.8%
200 mg x1 2 mg/kg x1
Ultra-Short INTRA
ZDV
300 mg
q 3 hr
POST
4 mg/kg bid
x1 wk
 NVP resistance 19% at 6-8 weeks (mothers),
46% at 6-8 weeks (infants)
Sources: Guay L.A. et al. Lancet 1999;354:795; Jackson J.B. et al. Lancet 2003;362:859
60
MTCT: Single-Dose Nevirapine vs ZDV/3TC
% Transmission:
Birth
Nevirapine
(variant of
INTRA POST
HIVNET 012)
versus
ZDV/3TC
(PETRA)
7.0%
200 mg x1 Mom 200 mg x1
Baby 2 mg/kg x1
INTRA POST
Q 3 hr Mom & baby
x1 wk
NVP resistance 6 weeks
67% moms, 53% infants
Btn Birth-8 Wks
5.7%
Overall, 8 wks: 12.3%
5.9%
3.6%
Overall, 8 wks: 9.3%
(Overall: p=0.11)
61
Source: Moodley D et al. JID 2003;187:725-35
Higher Transmission with Breast (N=623)
than Formula (N=694) Feeding
% Transmission
25
20
15
10
5
0
Birth
ZDV/
3TC
Formula
4 Weeks
Breast NVP
8 Weeks
Formula
Regardless of Treatment
Breast
62
Based on data from Moodley D. et al. JID 2003;187:725-35
Conclusions:
Nevirapine Prophylaxis Regimens
 When only intrapartum (IP)/postpartum (PP)
prophylaxis is given, single dose NVP is:
• Superior to IP/PP ZDV alone
• Similar to IP/PP ZDV/3TC
63
Pharmacokinetics of ARVs in Pregnancy
 Few trials evaluated the clinical significance of
physiologic changes during pregnancy on the
PK of commonly used drugs
 Half life of NVP is reduced from 66 hr in nonpregnant women to 45 hr in pregnant women
 Nelfinavir levels a third lower in pregnancy
 Unboosted IDV levels are sub-therapeutic, but
still may be indicated
 Pregnancy does not change the PK of ZDV, 3TC
and DDI
64
Risk of Development of Resistance: Mother
 Non-HAART regimens associated with the
development of resistance
 ZDV monotherapy: 0.3 - 14% risk of low-level ZDV
resistance
 ZDV + 3TC: 38% high-level 3TC resistance (ANRS
075)
 Nevirapine monotherapy: 15% - 18% high level NVP
resistance
► No longer detectable 12 months postpartum
65
Risk of Development of Resistance: Infant
 ZDV: longer courses (28 weeks) may result in
resistance transmission to the infant
 ~50% of infants develop NVP resistance
 The mutations are often different from the mother’s
because of de novo selection or emergence of a
mutant with greater fitness
66
Safety of NRTIs in Pregnancy
 Human pregnancy data only for ZDV, 3TC, DDI,
D4T
 No increase in birth defects have been observed
 Lactic acidosis and hepatic steatosis
 Rare, but potentially fatal syndrome
 Linked to prolonged use of NRTIs, esp DDI, D4T,
DDC (AVOID the use of DDI/D4T combination in
pregnancy)
 Vague symptoms
67
Safety of NNRTIs in Pregnancy
 Nevirapine single dose has not been associated
with adverse side effects in women and children
 Nevirapine resistance risk as above
 Nevirapine elimination may be accelerated in infants
whose mother received chronic nevirapine as part of
ART
 Pregnancy should be avoided in women
receiving efavirenz
 No human pregnancy data on long term use of
NNRTIs
68
Safety of PIs In Pregnancy
 Protease inhibitors associated with reduced
insulin sensitivity
 Pregnancy also associated with varying degrees
of insulin resistance
 Risk of diabetes greater with PI-containing
regimen
 Monitor fasting glucose and 2 hr GTT
 Avoid indinavir and liquid amprenavir
Source: Justman, 6th CROI
69
Data on the Use of ART During Pregnancy
 Category B
 Animal reproduction studies fail to demonstrate a risk to the fetus and
adequate but well controlled studies of pregnant women have not been
conducted
 Examples: DDI, FTC, TDF, Atazanavir, Nelfinavir, Ritonavir
 Category C
 Safety in human pregnancy has not been determined; animal studies
are either positive for fetal risk or have not been conducted
 Examples: ABC, 3TC, D4T, ZDV, NVP, DLV, Amprenavir
(fosamprenavir), Indinavir, Lopinavir/r
 Category D
 Positive evidence of human fetal risk that is based on adverse reaction
data from investigational or marketing experiences, but the potential
benefits from the use of the drug among pregnant women may be
acceptable despite it’s potential risks
 Example: EFZ
70
Summary: ARVs to Avoid in Pregnancy
 Efavirenz containing regimens
 Teratogenic
 DDI + D4T combination therapy
 Lactic acidosis
 Oral liquid formulation of amprenavir
 Propylene glycol
 Indinavir
• Avoid in late pregnancy (avoid use of unboosted IDV in
pregnancy)
71
Summary: Safety & Efficacy Issues in
Pregnancy
 HAART results in the lowest risk of transmission
to the infant
 Use of HAART best preserves mother’s future
therapeutic options
 Monitoring required for:
 Lactic acidosis/hepatic steatosis
 Rash, hepatotoxicity in women with CD4 >250
 Glucose intolerance
72
Summary: Antiretroviral Toxicities to
Fetus/Infant
 No increased risk of birth defects with exposure
to ARVs overall or for first trimester ZDV or 3TC
exposures
 No patterns of toxicity associated with
antiretrovirals within 5-10 years
 Mitochondrial toxicity may occur rarely
 Long-term studies underway to ascertain if
carcinogenic
73
Case Studies
Case 1
Case Study: Beza
 Beza is a 22 year-old woman newly diagnosed
with HIV who comes to the pharmacy to begin
antiretroviral therapy with NVP, 3TC and ZDV
 She is ready to start therapy and wants to be
healthy so that she can have a baby. She has a
new prescription for prenatal vitamins with her
that she would like to fill today
76
Case Study: Beza (2)

She asks you if it is okay to continue taking her
antiretrovirals (ART) should she become
pregnant. She has heard that ART can be
harmful to infants.
1. How would you counsel this patient?
2. Which antiretrovirals should be avoided in
pregnancy?
77
Case 2
Case Study: Tsegenet
 Tsegenet is a 34 year-old woman in her third
pregnancy who delivered a healthy 3.5 kg baby
girl an hour after she arrived at the maternity.
 After the birth, she told the staff she had a
positive HIV test done in clinic but did not take
the tablet given to her before rushing to the
maternity because she did not want her family to
know about her HIV infection
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Case Study: Tsegenet (2)
1. What treatment does Tsegenet require now?
2. What treatment does her baby require?
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Case 3
Case Study: Mihret
 Mihret, a 27 year-old female with a CD4 cell count of 182
cells/mm3 presents to clinic three weeks after starting
her new antiretroviral regimen. She states she has been
taking most of her medications. She admits to not always
practicing safe sex and is concerned about getting
pregnant. Her weight is 63 kg
 Her medical provider decides to start her on
norethindrone/ethinyl estradiol 0.5mg / 0.035 mg and
reinforces her need to use condoms
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Case Study: Mihret (2)
 Current Medications:




Stavudine 40 mg PO bid
Lamivudine 150 mg PO bid
Nevirapine (Viramune): 200 mg PO bid
Cotrimoxazole DS (160 mg/800 mg) PO qd
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Case Study: Mihret (3)
 Which of the following is TRUE regarding a
potential drug-drug interaction?
A) Nevirapine reduces the plasma levels of ethinyl
estradiol.
B) Nevirapine increases the plasma levels of ethinyl
estradiol.
C) Nevirapine reduces the plasma levels of
norethindrone
D) Nevirapine increases the plasma levels of
norethindrone
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Case 4
Case Study: Rahel
 Rahel, a 31 year-old, single HIV positive woman
came to the clinic with pain in her mouth and
chest upon swallowing. She had night sweats
and diarrhea for one month. Her usual weight
was 58 kg
 On exam she weighed 51 kg, had no palpable
lymph nodes, and had oral candidiasis. She
was diagnosed with presumed esophageal
candidiasis and treated with oral fluconazole for
2 weeks. Her pain subsided and she began to
eat
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Case Study: Rahel (2)
 Based on the esophageal candidiasis, she had
WHO Stage IV disease, although no CD4 count
was available.
 She began daily Cotrimoxazole for PCP
prophylaxis and was started on HAART at the
same time with stavudine 30 mg bid, lamivudine
150 mg bid, and efavirenz 600 mg qhs
 She has been adherent with her medications.
The night sweats and diarrhea have stopped,
her appetite has increased, and she has gained
6 kg
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Case Study: Rahel (3)
 At her 6-month follow-up visit she reports that
her menstrual period is 2 months late. A
pregnancy test is positive
 Should she continue her antiretroviral therapy?
 If she requires a change in her regimen, what
would you suggest as an alternative?
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Key Points
 Women are more susceptible than men to
contracting HIV through heterosexual
intercourse
 HIV infected women require special care
 Women are affected differently by HIV and ARVs
 Increased rates of certain toxicities in women
may be due to differences in drug metabolism
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Key Points (2)
 Issues to consider when starting treatment
include: preconception counseling, teratogenicity
of ARVs, drug interactions, efficacy, tolerability,
and co-morbidities
 Patients with AIDS are more likely to suffer from
pregnancy-related complications
 Transmission of HIV infection from mother to
child can occur during pregnancy, birth, or
breastfeeding
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Key Points (3)
 MTCT is the largest source of HIV infection in
children under 15
 HAART can reduce the risk of MTCT to less than
2%
 ART to reduce perinatal transmission must be
given to the mother and infant
 Regardless of treatment strategy, a higher rate
of transmission occurs with breast feeding rather
than formula
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