Transcript 2007 Women and HIV International Clinical Conference

2008 Women and HIV International
Clinical Conference
Reproductive Dilemmas for
Women Living with HIV
Carmen D. Zorrilla, MD
Professor Ob-Gyn
UPR School of Medicine
PI: UPR-CTU, PR-CCHD,CEMI
The Law of Choices:
Reclaiming our power
We are both burdened and blessed
by the great responsibility of free
will- the power of choice.
Our future is determined, in large
part, by the choices we make
now.
We cannot always control our
circumstances, but we can and do
choose our response to whatever
arises.
Reclaiming the power of choice, we
find the courage to live fully in
the world.
Dan Millman
The Laws of Spirit
Objectives
• To describe the issues and interventions to
deal with reproductive health particularly the
following:
• Infertility
• Preconceptional care
• Pregnancy considerations
Introduction
• HIV infection has changed from a life-threatening to
a chronic illness because of the availability of HAART
• Some of the behaviors that place women at risk for
HIV (IDU, Sex work) also place them at risk for
infertility
• Even though some women will postpone pregnancy
because of an HIV diagnosis, it will not change the
desire for reproduction
Pregnancy and HIV
• Transmission rates have decreased substantially
with current management (ART, C/S, infant formula)
• Current MTCT rates are around or less than 1%
• Pregnancy does not affect the progression of HIV
disease
• Women living with HIV do not have to postpone
pregnancies indefinitely
Infertility
• Seen in 10-15% of couples (general population)
• The factors may relate to the female (65%) or the male
(20%) and 15% unknown.
• Women living with HIV might have additional problems
due to the risks of STI’s and tubal occlusion.
• STI’s also increase the risk for pregnancy losses. HIV+
women might have more abnormal cycles (longer or
shorter) than controls*
• HIV + women might have anovulation and infertility
especially IDUs**
*Harlow S, Schuman P, Cohen M, et al Effect of HOV infection on menstrual cycle length. J.
Acquir Immune Defic Syndr 2000;24;68-75
** Chirgwin KD, Feldman J, Muneyyirci-Delale O et al. menstrual function in HIV infected women
without AIDS J. Acquir Immune Defic Syndr Hum retrovirol 1996;12;489-494
**Clark RA, Mulligan K, Stamenovic E, et al. Frequency of anovulation and early menopause
among women enrolled in select ACTG studies J infect Dis 2001; 184; 1325-1327
Fertility evaluation: History
• Menstrual cycle frequency (25-35 days), and quality
(dysmenorrhea is associated to endometriosis, abnormal or
profuse bleeding can be a symptom of fibroids)
• Changes in weight (>10 lbs)
• Signs of insulin resistance
• Concurrent medications (HAART)
• Exercise (vigorous exercise impairs fertility)
• Dieting
• Cigarette smoking (impairs fertility)
• History of STIs or PID
• Substance use (IDU, Heroin blocks ovulation, methadone
restores ovulation)
• Testosterone use (males)
Fertility Evaluation: Physical exam
• Body habitus (metabolic syndrome: GDM,
PCO)
• BMI (<18 and >27 related to decreased
fertility)
• Hirsutism (Poly Cystic Ovaries-PCO)
• Pelvic exam with signs of PID
• Males: testicular size
Fertility evaluation: Labs
•
•
•
•
Preconception counseling labs
Serum Prolactin and TSH
Tubal patency by HSG or laparoscopy
Ovarian reserve: day 3 FSH (>10-15 IU/L) abnormal
and estradiol (>75-80 pg/ml) abnormal
• Day #3 FSH > 25 or age> 44 equals close to 0%
success rate
• Ovulation tests:
– Progesterone >3ng/ml on day 21 (1 week before
menses)
– Positive LH (commercial ovulation kits) or
– BBT chart
Clomiphene Challenge Test
• An Assay of FSH response
• Patient takes 100mg on cycle day 5-9, FSH is
checked on day 3 & 10
• FSH >26 poor prospect for pregnancy
• Abnormal tests increase with age
– 3% in pts less than 30 y/o
– 26% in pts greater than 39 y/o
– 38% unexplained fertility…
Assisted reproductive technology
•
•
•
•
HIV+ female/HIV- male
HIV+ male/HIV- female
Both HIV+
Donor gametes
HIV+ woman/HIV- male
• If the male is HIV-, sperm is handled with the
usual precautions
• Check female health status: Low viral load,
high CD4, clinically stable, avoid efavirenz,
ddI, d4T
HIV+ woman/HIV- male
Techniques
• Self insemination (12-36 hrs after the LH peak)
using a syringe and an angio-cath
• Intrauterine insemination (IUI) when there is
oligospermia, semen is washed and resuspended
and it can be inserted into the uterine cavity (risks:
infection, anaphylaxis)
• Ovulation induction with Clomiphene
• Ovulation induction with Gonadotropins (FSH)
• In vitro Fertilization with embryo transfer (IVF-ET)
HIV- woman/HIV+ male
• HIV infection has been reported in 6 cases of
donor insemination*
• Some states regulate (control) the use of
“contaminated semen” and consider it as a
felony
*Wortley PM, Hammett TA, Flemming PL. Donor insemination and
HIV transmission Obstet Gynecol 1998;91:515-518
HIV- woman/HIV+ male
Techniques
• Sperm-washing and artificial insemination
(intrauterine) with nested PCR to detect HIV
in post wash sample has been used in Europe
(3,600 attempts with no seroconversions)*
*Semprini AE, Levi-Setti P, Bozzo M et al insemination of HIV- women with
processed semen of HIV+ partners
*Sauer MV. Sperm washing techniques address the fertility needs of HIV+
men: a clinical review Reprod Biomed Online 2005;10:135-140
Safety and Efficacy of Sperm Washing in HIV-1serodiscordant Couples Where the male is Infected:
Results From the European CREAThE Network
Bujan; Hollander; Coudert;Gilling-Smith; Vucetich;Guibert; Vernazza; Ohl;
Weigel; Englert; Semprini AIDS. 2007;21(14):1909-1914
• Sperm washing used to obtain motile spermatozoa for
3,390 assisted intrauterine inseminations, 107 IVF, 394
ICSI (intra-cytoplasmic sperm injections) and 49 frozen
embryo transfers.
• A total of 580 pregnancies were obtained from 3,315
cycles. Pregnancy outcome was unknown in 47 cases.
Safety and Efficacy of Sperm Washing in HIV-1serodiscordant Couples Where the male is Infected:
Results From the European CREAThE Network
Bujan; Hollander; Coudert;Gilling-Smith; Vucetich;Guibert; Vernazza; Ohl;
Weigel; Englert; Semprini AIDS. 2007;21(14):1909-1914
• The 533 pregnancies resulted in 410 deliveries and 463
live births.
• The result of female HIV testing after assisted
reproduction was known in 967 out of 1036 woman
(7.1% lost to follow-up).
• All tests recorded were negative.
• The calculated probability of contamination was equal to
zero (95% confidence interval, 0-0.09%).
Safety and Efficacy of Sperm Washing in HIV-1serodiscordant Couples Where the male is Infected:
Results From the European CREAThE Network
Bujan; Hollander; Coudert;Gilling-Smith; Vucetich;Guibert; Vernazza; Ohl;
Weigel; Englert; Semprini AIDS. 2007;21(14):1909-1914
Conclusions:
This first multicentre retrospective study of assisted
reproduction following sperm washing demonstrates the
method to be effective and to significantly reduce HIV-1
transmission risk to the uninfected female partner.
These results support the view that assisted reproduction
with sperm washing could not be denied to
serodiscordant couples in developed countries and,
where possible, could perhaps be integrated into a
global public health initiative against HIV in developing
countries
Tenofovir-Based HIV Postexposure Prophylaxis
K Mayer et al
J Acquir Immune Defic Syndr 2008;47:494-499
• 68 patients who presented after high-risk sexual exposure were
prescribed a course of tenofovir DF 300 mg and lamivudine 300 mg,
each given as one pill once a day, and a further 44 patients who
received a course of tenofovir DF 300 mg and emtricitabine 200 mg
(Truvada) given as a single fixed-dose tablet once daily, for NPEP.
• The treatment courses were completed by 87.5% of patients in the
tenofovir/lamivudine group and 72.7% of those in the
tenofovir/emtricitabine group. Adherence was significantly higher
than the 42.1% reported in 122 historical controls who were
prescribed 126 courses of zidovudine and lamivudine for NPEP
• No one in the tenofovir DF-containing NPEP groups became HIVinfected during the study period, whereas three individuals who
used zidovudine-containing regimens became infected during or
shortly after their course of NPEP (not statistically significant).
International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention
Pietro Vernazza et al St. Gallen Hospital (Switzerland)
Abstract
• 21 Serodiscordant couples where the men were already
taking antiretrovirals (HIV below the detectable level).
• The female partners received two doses of tenofovir,
one to be taken 36 hours before intercourse and another
12 hours before.
• After each of the couples had made three attempts, 11
of the 21 couples (52%) had conceived, after 10
attempts, 15 (71%) were pregnant.
• All the women in the study tested negative for HIV, 3
months after the last exposure.
Timed Intercourse
• Considered unsafe for serodiscordant couples
• Transmission risk is small (0.1-0.2%) but
cumulative exposure will increase the risk
• Unprotected intercourse during the following
2 days after the LH surge (ovulation kits)
• Consider timed intercourse with tenofovir
PREP*
* CZ
Both partners HIV+
• Risks of reinfection/superinfection and other
STIs
• Ideally: washed inseminations or IVF-ET
• Consider timed intercourse with tenofovir
PREP if the woman is not on ART*
Pregnancy Considerations
• Pre-conception Care is important for those
women living with HIV who have postponed a
pregnancy and want to achieve it now
• Therapy options might be different if you
acknowledge a potential future pregnancy
• For new patients in care, the suspicion and
detection of early pregnancy is crucial
Preconception Care
• The main goal of
preconception care is to
provide health promotion,
screening, and interventions
for women of reproductive
age to reduce risk factors
that might affect future
pregnancies
• It is part of a larger healthcare model that results in
healthier women, infants
and families
Recommendations to Improve Preconception
Health and Health Care –United States
MMWR April 21, 2006/Vol.55/No. RR-6
1. Improve the knowledge and attitudes and
behaviors of men and women related to
preconception health
2. Assure that all women of childbearing age
in the USA receive preconception care
services
Recommendations to Improve Preconception
Health and Health Care –United States
MMWR April 21, 2006/Vol.55/No. RR-6
3. Reduce risks indicated by a previous adverse
pregnancy outcome through interventions
during the interconception period, which
can prevent or minimize health problems for
a mother and her future children
4. Reduce the disparities in adverse pregnancy
outcomes
The law of expectation
Expanding our reality
Energy follows thought; we
move toward, but not
beyond, what we can
imagine.
What we asume, expect, or
believe creates and colors
our experience.
By expanding our deepest
beliefs about what is
possible, we change our
experience of life.
Dan Millman
The Laws of Spirit
Preconception counseling and care specifically
recommended for HIV-infected women
DHHS Perinatal Guidelines November 2, 2007
a.
b.
c.
Select effective and appropriate contraceptive methods
to reduce the likelihood of unintended pregnancy.
Providers should be aware of potential interactions of
antiretroviral drugs with hormonal contraceptives that
could lower contraceptive efficacy.
Counsel on safe sexual practices that prevent HIV
transmission to sexual partners and protect women
from acquiring sexually transmitted diseases (STDs)
and the potential to acquire more virulent or resistant
HIV strains.
Counsel on eliminating alcohol, illicit drug use, and
cigarette smoking.
Interactions Between Anti-HIV Drugs and OC’s
Antiretroviral
Interaction
Recommendation
Delavirdine
Ethinyl estradiol levels may
increase
Clinical significance unknown
Efavirenz
37% increase in ethinyl
estradiol
No interaction with depomedroxyprogesterone
Use alternative or additional
method of contraception if
using oral contraceptives
Nevirapine
Approximately 20% decrease in Use alternative or additional
ethinyl estradiol
method of contraception if
No interaction with depousing oral contraceptives
medroxyprogesterone
Amprenavir
Increase in ethinyl estradiol and Do not coadminister; use
norethindrone levels observed alternate method of
with amprenavir; 20% decrease contraception
in amprenavir levels
Atazanavir
48% increase in ethinyl
estradiol AUC, 110% increase
in norethindrone AUC
Use lowest effective dose or
alternative methods
Interactions Between Anti-HIV Drugs and OC’s
Antiretroviral
Interaction
Recommendation
Darunavir/ritonavir
Potential decrease in ethinyl
estradiol
Use alternative or additional method
of contraception
Fosamprenavir
Increase in ethinyl estradiol and
Do not coadminister; Use alternate
norethindrone levels observed with method of contraception
amprenavir; 20% decrease in
amprenavir levels
Indinavir
26% increase in norethindrone;
24% increase in ethinyl estradiol
No dose adjustment
Lopinavir/ritonavir
42% decrease in ethinyl estradiol
Use alternative or additional method
of contraception
Nelfinavir
18% decrease in norethindrone;
47% decrease in ethinyl estradiol;
no interaction with depomedroxyprogesterone
Use alternative or additional method
of contraception if using oral
contraceptives
Ritonavir
40% decrease in ethinyl estradiol
Use alternative or additional method
of contraception
Saquinavir
No data
No data
Tipranavir/ritonvir
Approximately 50% decrease in
ethinyl estradiol Cmax
Use alternative or additional method
of contraception
Preconception counseling and care specifically
recommended for HIV-infected women
DHHS Perinatal Guidelines November 2, 2007
d. Educate and counsel women about risk factors for perinatal HIV
transmission, strategies to reduce those risks, and potential effects
of HIV or treatment on pregnancy course and outcomes.
e. When prescribing antiretroviral treatment to women of childbearing
potential, considerations should include the regimen’s effectiveness
for treatment of HIV disease and the drugs’ potential for
teratogenicity should pregnancy occur. Women who are planning to
get pregnant should strongly consider use of antiretroviral regimens
that do not contain efavirenz (EFV) or other drugs with teratogenic
potential. In addition, the effectiveness of a regimen in preventing
mother-to-child HIV transmission should be considered.
Preconception counseling and care specifically
recommended for HIV-infected women
DHHS Perinatal Guidelines November 2, 2007
f. Attain a stable, maximally suppressed maternal viral load prior to
conception in women who are on antiretroviral therapy and want to
get pregnant.
g. Evaluate and control for therapy-associated side effects that may
adversely impact maternal-fetal health outcomes (e.g.,
hyperglycemia, anemia, hepatic toxicity).
h. Evaluate for appropriate prophylaxis for opportunistic infections and
administration of medical immunizations (e.g., influenza,
pneumococcal, or hepatitis B vaccines) as indicated.
i. Encourage sexual partners to receive HIV testing and counseling and
appropriate HIV care if infected.
Preconception counseling and care specifically
recommended for HIV-infected women
DHHS Perinatal Guidelines November 2, 2007
j. Counsel regarding available reproductive options, such as
intrauterine or intravaginal insemination, that prevent
HIV exposure to an uninfected partner; expert
consultation is recommended.
k. Breastfeeding by HIV-infected women is not
recommended in the United States due to risk of HIV
transmission.
Issues with antiretroviral use in pregnancy
• Antiviral Drug resistance testing
• Choice of drugs: PI vs non-PI
• Missing Pregnancy PK data on new drugs
(amprenavir, atazanavir, darunavir)
• New classes of drugs: CCR5, entry inhibitors
• New formulations:
– Lopinavir/ritonavir capsule (lpv 133/rtv33mg) no longer
available, no data on tablets (lpv 200/rtv 100mg)
– Saquinavir SGC (sqv 800/rtv100 mg had good PK in
pregnancy);1,200 mg SQV-hgc/50 mg RTV with AUCs above
10,000 ng • h/mL (n=2)
*Lopez-Cortes, L. F., R. Ruiz-Valderas, R. Pascual, M. Rodriguez, and A. Marin
Niebla. 2003. HIV Clin Trials. 4:227-9.
Nelfinavir (Viracept)
Contamination with ethyl methane sulfonate
• Last summer, Viracept was recalled from the European and
US market due to high levels of a harmful substance known
as ethyl methane mesylate (EMS), a byproduct of the Viracept
manufacturing process. EMS is known to be an animal
carcinogen (can cause cancer) mutagen (can be harmful to
DNA, the genetic material in cells) and a teratogen (can be
harmful to the development of an unborn child). The level at
which EMS may become carcinogenic in humans is not
known.
The DHHS Panel on Treatment of HIV-Infected
Pregnant Women and Prevention of Perinatal
Transmission Recommendations:
• When considering the risk/benefits for use of Viracept
(nelfinavir), the needs of the individual patient must always
be considered.
• Pregnant women who need to begin antiretroviral therapy or
prophylaxis should not be offered regimens containing
Viracept (nelfinavir) until further notice, but rather begin an
alternative antiretroviral regimen.
• Pregnant women who are currently receiving Viracept
(nelfinavir) should be switched to an alternative antiretroviral
regimen.
• For pregnant women with no alternative treatment options,
the risk-benefit ratio remains favorable for the continued use
of Viracept (nelfinavir) in these women.
Management
Pediatric Patients
• For pediatric patients who are
stable on Viracept-containing
regimens, the FDA and Pfizer
agree that the benefit-risk ratio
remains favorable and those
patients may continue to receive
Viracept.
• Pediatric patients who need to
begin HIV treatment should not
start regimens containing
Viracept until further notice.
Other Patients
• There is no change in the
recommended use of
Viracept for all other
patients.
Recommendations
• Preconceptional care as part of routine care
for women living with HIV
• Need for provider self-acknowledgement of
beliefs and values before reproductive issues
are discussed or managed
• It is better to refer than to deny options
The law of compassion
Awakening our humanity
The universe does not judge us;
it only provides consequences
and lessons and opportunities
to balance and learn through
the law of cause and effect.
Compassion is the recognition
that we are each doing the
best we can within the limits
of our current beliefs and
capacities.
Dan Millman
The Laws of Spirit
Measure time, if you
must, in lessons
learned, not in minutes
or hours or years.
Brian Weiss
Only Love is Real