HIV AND WOMEN’S HEALTH Anandi Sheth, MD October 15, 2013

Anandi Sheth, MD
Emory University Division of Infectious Diseases
October 15, 2013
Epidemiology – Global
~50% of people living with HIV are women
~47% of new infections occur in women
Disproportionate impact on women in sub-Saharan Africa
 Particularly among young women (3-8 times increased HIV, AIDS
leading cause of death)
Women >15yo living with HIV, 1990
Women >15yo living with HIV, 2012
Epidemiology - US
Shift towards increased HIV incidence in women
in the US (now ~20% of new cases)
Racial disparities are magnified in women
Higher-than-expected concentrations in the
Southern US
Women and HIV Transmission
Sociobehavioral factors:
May not be able to negotiate consistent condom use
 Violence increases HIV risk through multiple mechanisms
 Stigma, poverty, substance abuse, other comorbid conditions
Biological factors:
Higher risk of HIV acquisition than men during vaginal sex
Large surface area
 Concomitant STIs/ inflammation/ mucosal trauma
 Hormonal effects on mucosa
High risk of transmission during anal sex
Access to Care and Natural History
Data are mixed, but some studies suggest gender
differences in timing of diagnosis, access to care,
progression to AIDS
Barriers to entry and retention in care
 Transportation,
child care, work schedules,
economics, insurance, stigma, mental health/
substance abuse
ART in Women
Generally, response to ART is comparable between men and
Adherence also similar, though may have different reasons for
Women may have increased risk of ART-associated complications
Lactic acidosis due to NRTIs
Rash and hepatitis due to nevirapine use discouraged in women
with CD4>250 (>400 for men)
PI-associated nausea/vomiting
Bone loss
Fat accumulation
In general, treatment guidelines are the same for men and
women with few exceptions
HIV-associated conditions unique to
Candida vulvovaginitis (recurrent) – most common presenting sx of HIV infection
in women!
Cervical dysplasia and cancer
Recurrent/ complicated PID
Increased frequency/ severity of genital HSV
Increased/ persistent BV
Abnormal uterine bleeding
AIDS-defining conditions: invasive cervical cancer, genital tract TB, genital tract
lymphoma, other genital tract OI (ex., CMV endometritis)
 Screen for GU disease routinely (q6mo-annual), after potential exposures or new
sexual partner
Case 1
35yoF with HIV, newly diagnosed, CD4=387, VL 27K,
presents for new patient appointment. She was
diagnosed by routine testing with her PCP, has no
history of abnormal Pap or genital HPV, and is
asymptomatic. How should she be screened for
cervical dysplasia?
A. Pap and HPV testing now. If normal, repeat annually.
B. Pap now. If normal, repeat in 6 months.
C. Pap now. If abnormal, repeat in 6 months.
D. Colposcopy now.
E. Pap now. If abnormal, colposcopy in 6 months.
HPV-related disease in HIV-infected
Clinical manifestations of HPV infection:
Oral, genital, and anal warts (condyloma acuminata)
Cervical, vaginal, vulvar, anal dysplasia and cancers, subset of
oropharyngeal cancers
HIV-infected women are ~10x more likely to have abnormal
Pap than HIV-uninfected women
Increased persistence of HPV and/or
progression of dysplasia, higher
cervical cancer risk
Genital warts, vulvar dysplasia, and
anal dysplasia (~25%) also common!
Credit: AETC HIV Screening and Women’s Health
Screening Guidelines in HIV-infected
Screen with Pap every 6 months in the first year after diagnosis
Screen annually afterwards
Consider screening within 1 year of onset of sexual activity regardless of age
After hysterectomy, do vaginal cuff Pap if patient has history of CIN or cervical CA
Colposcopy depending on cytology +/- HPV DNA per guidelines
Role of HPV testing (detects most oncogenic HPV types) in HIV-infected women has
not been established
Limited data on HPV vaccine (studies underway), recommended for HIV-infected
males & females 13-26 (prefer <19)
 Differ from guidelines for HIV-negative women (extend screening interval to 3-5 years
in women >30yo with normal cytology and negative oncogenic HPV DNA test results)
Should screening guidelines change
for some HIV-infected women?
420 HIV-infected vs. 279
uninfected women
Enrolled 2001-2002 after widespread use of HAART
Normal cervical cytology at enrollment, HPV testing performed
Conducted q6month Pap testing with appropriate follow-up
Results: similar (and low) 5-year cumulative incidence of cervical
precancer or cancer (HSIL+ or CIN2+) in oncogenic HPV-negative
HIV-infected vs. -uninfected women
Case 2
26yoF with HIV, CD4=300, VL undetectable on atripla.
She is planning to get pregnant in the next 1 year. You
should recommend that she do the following:
A. Continue atripla because her VL is undetectable
B. Discontinue atripla because tenofovir may be
C. Discontinue atripla because efavirenz may be teratogenic.
D. Continue atripla until she conceives. Then hold ART
during the first trimester.
E. She should receive a regimen containing zidovudine.
When does mother-to-child
transmission occur?
Overall risk of transmission without treatment - ~25%
In utero
<14 weeks (4%)
14-36 weeks (16%)
36 weeks+ (50%) ***
Intra-partum (30%)
Breastfeeding (?)
Conditions that may increase risk: maternal viral load,
maternal genital tract infections/ inflammation,
prolonged rupture of membranes
PACTG 076: Zidovudine for prevention
of mother-to-child transmission
477 pregnant HIV-infected women received AZT versus placebo as
100mg po 5x per day from 14-34 weeks
Intrapartum 2mg/kg iv x 1 followed by 1mg/kg until delivery
6 weeks oral for infant (2mg/kg q6h for 6 weeks started 8-12h after birth
Study halted in 1994 when 66% reduction in transmission noted in
treatment group (7.6% versus 22.6)
Became the standard for comparison of other regimens
Subsequent regimens including cART have reduced transmission to
<2% (see pages B7-B15 of perinatal guidelines
( for a complete list of studies
Current guidelines to reduce
perinatal transmission
Opt-out testing for pregnant women
 Pregnancy
increases HIV acquisition risk, so repeat HIV
test in the 3rd trimester in at-risk women!
 If woman presents without antenatal care, do rapid test,
initiate prophylaxis in mother and infant if rapid test is
positive (do not wait for confirmatory test)
Assess for risk factors for transmission: plasma
viremia, genital infections, drug use, unprotected sex
Screen for Hepatitis B and C
Current guidelines to reduce
perinatal transmission, continued
All pregnant women start ART regardless of CD4 and VL (see next
Intravenous AZT during delivery
C section at 38 weeks if VL >1000 copies/mL (at 39 weeks of other
indication for C-section)
Avoid invasive fetal monitoring, vacuum delivery or forceps during
vaginal delivery, avoid artificial or prolonged ROM
Postpartum care:
Continue ART (if CD4>500 discuss with patient)
Avoid breastfeeding if access to clean water and formula
Counsel on contraception
ART during pregnancy
All drugs listed have high placental transfer to the fetus
Zidovudine, lamivudine
*If Hep B co-infected: tenofovir + lamivudine/emtricitabine
Abacavir, emtricitabine ,tenofovir
Nevirapine (not if CD4>250 or baseline transaminmitis)
Efavirenz (Class D- test for pregnancy before initiating EFV-containing
regimens, do not use in women who are planning to become pregnant, may
be continued in women who are undetectable presenting for ant
Atazanavir/ ritonavir, lopinavir/ritonavir: dose adjust in the 2nd-3rd trimester
Darunavir/ ritonavir
Other classes
Use in special circumstances (insufficient data, no known teratogenicity)
In general: if a women is controlled already, continue the regimen:
Monitoring: VL baseline, 2-4 weeks after ART start or change, monthly until undetectable,
q3mo during pregnancy, and at 34-36weeks to decide on mode of delivery
If amniocentesis is needed- do after effective ART and VL undetectable
WHO Guidelines (2010, 2013)
2010: start ART for all pregnant women with CD4<350 or stage
3/4 disease at 14 weeks, continue lifelong
2013: all pregnant women regardless of CD4 count start ART
AZT/3TC or TDF/3TC plus NVP or EFV  2013 changed to
Two options for prophylaxis (2010):
Option A: twice daily AZT for mother and AZT or NVP for infant for 6
weeks or until 1 week after end of breastfeeding
Option B: three-drug prophylaxis for mother during pregnancy and
breastfeeding, and infant prophylaxis for 6 weeks after birth
regardless of breastfeeding
Option B+: mother continues three-drug treatment for life
Reproductive options for HIV
sero-discordant couples
Perinatal guidelines:
Case 3
24yoF with perinatal HIV infection complicated by poor adherence and
multi-class resistance. She was lost to follow-up 2 years ago, during
which she became pregnant, was started on ARVs without VL
suppression during pregnancy. She has been off ARVs since time of
delivery, presented to resume care, CD4=8, VL 189K. She is sexually active
with 1 male partner and inquires about contraception options. Which of
the following is true:
A. Combination oral contraceptives will be less effective due to ART
B. Starting oral contraception will increase risk of HIV transmission to her
male partner
C. An IUD is contraindicated because it will increase her risk of PID
D. Injectable contraceptives are associated with increased risk of HIV disease
E. All of the above
F. None of the above
Importance of Family Planning in PMTCT
Medical eligibility criteria for
contraceptive use
WHO 1: Use without restriction
WHO 2: Can use (advantages outweigh risks)
WHO 3: Don’t use unless you have to (Risks outweigh
WHO 4: Do not use (Unacceptable health risk)
Our patients may have other conditions (besides HIV/AIDS or ARV use) that
affect contraceptive eligibility
MMWR vol 59 (2010); WHO 2009
Barrier methods
Condoms (WHO 1)
Spermicides/microbicides (WHO 3/4)
Latex condom failure rate ~15% with typical use (2% perfect use)
Rupture 0.5-4% (deterioration, poor storage, oil lubricants)
Failure rate similar for female condom, acceptability less
Dual method recommended for HIV+ women (condom plus other)
Increased risk of STI (HIV) acquisition
Studies in progress
Diaphragm/ cervical cap (WHO 3/4)
Failure rate 19-32% with typical use
Requires spermicide
Combined Hormonal Methods
Combined Pills
 Efficacy
?reduced by abx (backup first 2 wks of TMP/SMX)
 Overall, no increased HIV transmission/ acquisition risk
Vaginal ring (Nuvaring)
 Active
for 3-5 weeks, need backup if removed >3 hours
Patch (Evra)
 Active
for up to 9 days
 Higher failure in women >90 kg
Failure 8% (typical use), 0.3% (perfect use)
NRTIs (WHO 1), NNRTIs (WHO 2), RTV-boosted PI (WHO 3)
Injectable (Depo-provera)
Failure rate same as combined methods
Side effects: irregular bleeding, less forgiving if taken late, mood
NRTIs (WHO 1), NNRTIs (WHO 2), RTV-boosted PI (WHO 3)
Failure 3% with typical use (0.3% perfect use)
Side effects: irregular bleeding, weight gain, hair loss
? Risk of CIS with long-term use if persistent HPV infection
WHO 1 for all ARVs
Insert (Implanon)
Lasts 3 years
Failure 0.05%
Side effects: irregular bleeding
WHO 1/2 for all ARVs
Failure 0.8%
 Lasts 10-12 years
 Side effect: irregular bleeding
 May have decreased disease progression compared with
hormonal methods
Levonorgestrel intrauterine system (Mirena)
Releases hormone locally
 Failure 0.2%
 Lasts 5 years, can become pregnant as soon as its removed
 Improves dysmenorrhea, decreased menstrual flow (long
May have short term increased menstrual irregularity
Both: WHO 2 (except if AIDS WHO 3 because of ?increased PID risk)
Drug Interactions with ARVs
NRTIs, RAL, MVC: all methods ok
EFV ↓ norgestimate metabolites (many oral)- don’t use; possibly ↓ etonogestrel (implant), ↓ levonorgestrel
(emergency contraception)
NVP guidelines conflicting but probably ok
Boosted PIs
In general, ↓ethinyl estradiol and progestin (except ATV)
Don’t use oral methods with any except
ATV/r (≥35mcg of ethinyl estradiol in combined)
ATV (≤ 30 mcg ethinyl estradiol in combined)
DMPA ok, implants not studied
↑ progestin, ↓ ethinyl estradiol consider alternative because possible increase side effect of progestin
Some data suggest ovulation still suppressed even if ethinyl estradiol is decreased!
Effect on ART efficacy not well studied (monitor carefully…)
Check for drug interactions with other meds and for other medical contraindications!
Intersection between HIV and intimate
partner violence (IPV)
CDC Definition:
Physical, sexual, or psychological harm by a current
or former partner or spouse. This type of violence
can occur among heterosexual or same-sex couples
and does not require sexual intimacy.
IPV and HIV risk: how are they
Childhood abuse
coping strategy
increased vulnerability
Less condom negotiation
transactional sex
i.e. intravenous
drug use
Increased sexual partners
Courtesy of A Kalokhe
High IPV prevalence in HIV-infected
IPV prevalence among HIV-infected populations
ranges from 39-93%
Among inpatient HIV+ crack cocaine users from
Atlanta and Miami, 56% reported any IPV, 26%
reported severe IPV
associated with increased unprotected sex,
increased STIs, and not using ART
 38% did not use any IPV resources
Kalokhe et al 2012
Screening for IPV
(adapted from a validated screener: Paranjape A. J Natl Med Assoc. 2006 )
Were you ever in a relationship in which:
a sexual partner beat, physically attacked, or
physically abused you?
a sexual partner sexually attacked, raped, or sexually
abused you?
a sexual partner threatened you with violence (i.e.
acts of aggression or abuse that were meant to harm
a sexual partner threw, broke, or punched things?
you felt controlled by a sexual partner?
Courtesy of A Kalokhe
Types of IPV experienced
Reported being in a
relationship in which:
a sexual partner was physically
20 (12%)
74 (43%)
94 (27%)
a sexual partner was sexually
10 (6%)
50 (29%)
60 (17%)
a sexual partner threw, punched,
or broke things
64 (38%)
96 (56%)
160 (47%)
a sexual partner threatened the
participant with violence
49 (30%)
100 (58%)
149 (43%)
felt controlled by a sexual partner
45 (27%)
97 (56%)
143 (42%)
Courtesy of A Kalokhe
Short, Easy, Sensitive and Specific IPV
Screening Tools: find them on-line
• HITS (Hurt, Insult, Threaten, Scream)
• STaT (Slapped, Threatened, and Throw): developed at Grady!
• HARK (Humiliation, Afraid, Rape, Kick)
• CTQ-SF (Modified Childhood Trauma Questionnaire–Short
• WAST (Woman Abuse Screen Tool)
Courtesy of A Kalokhe
IPV Resources at IDP and beyond
Discussion is encouraged during HIV pre-test counseling
IPV risk assessment is required for post-test counseling
Consider poor adherence, missed visits, etc. as a proxy for
Also consider when you are discussion HIV status
disclosure, safe sex counseling
At IDP: Mental health, substance abuse, financial
Referral to IPV services
Partnership Against Domestic Violence has a 24-hour crisis line:
Igho Ofotokun
Lisa Haddad
Ameeta Kalokhe