HIV in
Women
Karin Nielsen M.D., MPH
David Geffen School of Medicine at UCLA
Images provided by iStock International Inc. All rights reserved. All copyrights held by the respective photographers. Used by permission. People in pictures are not necessarily HIV positive.
HIV in Women — Worldwide
2013:
Nearly half of
the more than 40
million HIV infections
worldwide are in
women
Women make up over
60% of 15- to 24year-olds living with
HIV/AIDS
UNAIDS. AIDS Epidemic Update: December 2005.
World Youth Report, 2003: HIV/AIDS and Young People.
HIV prevalence among pregnant women
in South Africa, 1990 to 1999
HIV prevalence (%)
25
22.8
22.4
98
99
20
17
14.2
15
10.4
10
7.6
5
4
1.7
2.1
91
92
0.7
0
90
93
94
95
96
Source: Department of Health, South Africa
97
HIV in Women in the United
States
 In
U.S., women account
for nearly 1 in 4 of new
HIV infections
 In some states, 3 out of 4
new HIV infections occur
in women (mostly women
of color)
 84% of new HIV infections
in women in 2010 were
transmitted by boyfriends
or husbands.
UNAIDS. AIDS Epidemic Update: 2010.
HPTN 064
HIV Prevalence 8% or
greater in selected
US populations
5
Snapshot of the Epidemic
 280,000 of 1.1 million
people living w/ HIV in the
U.S are women (24%).
 Women were 20% of new
HIV infections in 2010,
21% decrease since 2008
 In 2011, 8102 new AIDS
diagnoses in women, 25%
of AIDS diagnoses
 ¼ AIDS deaths in 2010
were in women.
Where Are All the HIV+
Women?
 Women
are diagnosed with HIV
later than male counterparts
 Most women are diagnosed with
HIV when pregnant, considering
pregnancy, or admitted to
hospital with acute illness
 Once diagnosed, up to 25% of
women postpone treatment
 Many women choose not to
disclose their status.
HIV distribution by race

Women of color are most affected by HIV:
– Majority of new infections (2/3, 64% of new infections in
women are in Black women) although Black women
comprise only 13% of female population in the U.S.
– Highest number of women living with HIV (60%); 19%
Latinas, 18% White.
– Likelihood of an HIV diagnosis is 20 x higher for a black
woman as compared to white and 4 x higher as compared
to Latina:
» Black: 38 per 100,000
» White: 1.9 per 100,000
» Latina: 8.0 per 100,000
What Happens with untreated
HIV-1 Infection
Plasma Levels
Plasma Viral Load
Peripheral Blood
CD4+ T-Cell Count
AIDS = CD4<200
Weeks
Years
Acute Infection
Chronic Infection
HIV Meds
NRTI
Nucleoside reverse transcriptase inhibitor (NRTI), also called a “nuke”
NNRTI
Non-nucleoside reverse transcriptase inhibitor (NNRTI), also called a “non-nuke”
PI
Protease inhibitor (PI)
II
Integrase inhibitors (II)
R5I
CCR5 receptor antagonist (attachment inhibitor)
FI
Fusion inhibitor (FI)
– There are 6 classes of drugs for HIV.
– An HIV treatment regimen is typically
composed of 3 medications
How Do the Drugs Work?
Lifecycle of the HIV Virus
Healthy cell
Virus
attaches
to cell
Protease
(CD4)
Infected cell
produces
new virus
Virus fuses
to cell
HIV virus
Integrase
Virus enters cell
Reverse
transcriptase
Goals of HIV Treatment
Goal 1: Keep your viral load as
low as possible
Goal 2: Keep your CD4 cell count up
Goal 3: Prevent transmission
Why is taking meds so important?


Adherence (taking all meds at the correct dose and
correct intervals) is important because taking
medicines as directed helps keep the virus from
making new copies of itself.
Billions of viral particles can multiply in someone’s
body every day, so to keep them under control, it’s
important that medicines are taken every day.
Why is adherence so
important?
Staying adherent helps keep individuals healthy
and prevents:
1. Viral load from going up
2. CD4 cell count s from going down
3. Development of viral resistance
1. Viral load going up

When someone misses
doses, there’s not enough
medicine in the body to
fight the virus, and the viral
load goes up
– HIV is under control when
the viral load is down.
2. CD4 cell count going down
When
individuals miss
doses, the viral load
goes up, so there is
more virus to attack the
immune system and
bring the CD4 cell count
down
3. Developing resistance

When individuals miss doses, the virus can
become “resistant” to HIV medicines
– The virus has to multiply to develop mutations that
cause resistance- “no mutation without replication”
– Resistance means changing HIV medicines
– When a virus is resistant, it has found ways to
outsmart HIV medicines and makes copies of itself
faster than before
3. Developing resistance

Skipping doses can lead to “mutations” of the
virus
– Mutations are copies that are slightly different than
the original and your HIV medicines cannot fight
them
Why do people miss doses
of their HIV medicines?
Too many pills
Confused about
when to take pills
Forgot to
take pills
Too buy to take them
Side effects
that are hard
to live with
Medicines that have
to be taken with
food or without food
Poor access to care
HIV Medications in Our Bodies
How Women Differ
Drug
interactions
Lower body
weight
Liver
metabolism
Higher body
fat content
Effects of
pregnancy
Hormonal
differences
Hader SL, et al. JAMA. 2001; DHHS. Guidelines…, February 2002 • Garcia PM, et al. Clinical Update. 2000 • Anderson GD.
J Gend Specif Med. 2002 • Mirochnick M. Ann NY Acad Sci. 2000 • Mildvan D, et al. J Acquir Immune Defic Syndr. 2002
What About All Those Side Effects?
 All
HIV drugs can cause
side effects
 Some people experience or
notice side effects less
 Side effects are most
common in the first 4 to 6
weeks after starting a new
medication—after that,
many lessen or go away
completely
 Lipodystrophy and lactic
acidosis are exceptions
Antiretroviral toxicity
Minor side effects
 Hepatitis
 Skin rashes
 Diabetes
 Lipodystrophy
 Mitochondrial toxicity

Do Men and Women with HIV Progress at the Same Rate?
Progression of HIV Disease in Women Receiving HAART



No difference in disease progression found between
women and men in recent studies
of HAART
Women in several longitudinal trials tend to show
baseline differences with men
– Younger age, lower viral load, higher CD4 cell counts
at time of treatment initiation
When adjusted for variables, response to ART is similar
between sexes
Jarrin I. 14th CROI, San Francisco 2007, Poster 776.
Moore AL. JAIDS. 2003;32:452-46.
Nicastri E,. AIDS. 2005;19:577-583.
Gender Differences in Quality of HIV Care in Ryan White
- Funded Clinics
Women were less likely than men to
receive
Women
Men
100%
82%
 HAART
80%
78%*
75%
†
 PCP prophylaxis
 Have their hepatitis C virus status
known
Percent (%)
65%
60%
40%
20%
despite being seen more regularly
(69% vs. 66%, P=0.04).1
0%
On HAART
On PCP Prophylaxis
*P<0.001 vs men. †P<0.0001 vs men.
Hirschhorn LR, et al. Women’s Health Issues. 2006;16:104-112.

Treatment study of patients with advanced HIV disease
in Africa, Asia, Caribbean, North and South America:
CD4 cell counts over time following treatment initiation
Figure 2
CD4+ Lymphocytes
-3
Change from Screening (mm )
450
Women
Men
400
350
300
250
200
150
100
50
Women 706
Men 784
P-value 0.95
24
686
765
0.05
677
732
0.05
666
703
0.002
653
675
<0.001
48
96
120
144
Week
560
563
0.005
168
355
337
0.12
192
Medical Complications in
HIV+ Women
Increased Complications
in Women
Side effects
Sexually
transmitted
infections
Gynecologic
problems
Contraception
and Pregnancy
issues
Lipodystrophy
and Diabetes
Depression
Cancer
Bone
thinning
Lactic Acidosis
 Lactic
acidosis is an increase of lactic acid in the
blood
 Symptoms include:
– Feeling very weak or tired
– Having unusual muscle pain
– Having trouble breathing
– Having stomach pain with nausea and vomiting
– Feeling cold, especially in arms and legs
– Feeling dizzy or lightheaded
– Having a fast or irregular heartbeat
Lipodystrophy
 in fat in the blood (cholesterol and
triglycerides)
 Changes in face, breast size, and body
shape
  risk of diabetes
  risk of heart problems

Lipodystrophy
What Can Be Done?
Review HIV medications
 Exercise
 Healthy diet
 No smoking
 Cholesterol-lowering drugs

Gynecological (GYN)
Problems



HIV+ women have more GYN infections that
are more difficult to treat than infections in
HIV negative women
Untreated vaginal infections can lead to
serious illnesses and strain the immune
system
HIV+ women should receive regular GYN
care from a doctor who is knowledgeable
about GYN conditions in HIV+ women
Gynecologic Complications In HIV




STDs more frequent
Complications more
common
Treatment failure
more common
Presentation may be
atypical or
prolonged





HSV infectionsrecurrent
Bacterial vaginosis
Syphilis
Vaginal yeast
infections recurrent
HPV leading to
cervical cancer
Menstrual Disorders



WIHS and HERS cohort--802 HIV+ v. 273 HIV
– women. Found very short or very long cycles in
HIV+ with < 200 CD4 count or high viral loads.
Otherwise cycles similar controlling for weight, age
and substance abuse.
Majority of HIV+ women ovulate
Abnormal bleeding in HIV + women should be
evaluated more closely in advanced patients to rule
out carcinoma, uterine lymphoma, genital tract TB or
CMV endometritis
Cancer
Some cancers are increased with HIV
infection
 PAP smears should be performed more
frequently in women with HIV
 More skin cancers in HIV- sunblock and
protective measures.
 Risk of breast cancer similar to non-HIVinfected women but regular mammograms
should be performed.

HIV Transmission
Low Probability Event
Women are more susceptible than men to contract HIV during
unprotected heterosexual intercourse
Stage of
Disease
in Partner
Factors that Impact the
Risk of Transmission
Exposure
site
STDs
Vaginal
Practices
Role of
contraception
Circumcision
Age
HAART
A Randomized Controlled Trial
 To determine if ART reduces HIV-1
transmission
• magnitude?
• durability of benefit?
 To determine if ART is used “earlier” to
reduce HIV-1 transmission
• personal health benefit(s)?
HPTN 052 Study Design
Stable, healthy, serodiscordant couples, sexually active
CD4 count: 350 to 550 cells/mm3
Randomization
Immediate ART
CD4 350-550
Delayed ART
CD4 <250
Primary Transmission Endpoint:
Virologically-linked transmission events
Primary Clinical Endpoint
WHO stage 4 clinical events, pulmonary tuberculosis, severe
bacterial infection and/or death
HPTN 052 Enrollment
(Total Enrollment: 1763 couples)
U.S.
Thailand
India
Kenya
Americas
278
Brazil
Botswana
South Africa
Malawi
Zimbabwe
Africa
954
Asia
531
HPTN 052: HIV-1 Transmission
Total HIV-1 Transmission Events: 39
Immediate Arm
4
Delayed Arm
35
p < 0.0001
HPTN 052: HIV-1 Transmission
Total HIV-1 Transmission Events: 39
Linked
Transmissions: 29
Unlinked or TBD
Transmissions: 10
• 18/28 (64%) transmissions from infected
participants with CD4 >350 cells/mm3
Immediate
Arm: 1
Delayed
Arm: 28
p < 0.001
• 23/28 (82%) transmissions in sub-Saharan
Africa
• 18/28 (64%) transmissions from female to
male partners
HPTN 052 Prevention Conclusion
Early ART that suppresses viral replication led to
96% reduction of sexual transmission of HIV-1 in
serodiscordant couples
Current Preventive Strategies
Can We Do Better for Women ?
Microbicides


a substance that can reduce
transmission of STDs and HIV when
applied either in the vagina or
rectum.
gels, creams, suppositories, films,
lubricants, or in the form of a sponge
or a vaginal ring

Cheap and nontoxic

Contraceptive properties

Act as physical barrier, maintain
acidic pH , prevent viral replication
(PMPA) or entry
HIV and Sexuality
Women and men sometimes stop
dating or having relationships after their
HIV diagnosis
 Fear of talking about their HIV status is
common
 Vaginal infections may make sexual
relations more painful
 Women with HIV and AIDS can still get
pregnant

What about Birth Control?
Condoms are efficacious if used
consistently
 Condoms fail, however, so a back-up
method is good to prevent pregnancies
 HIV therapy interacts with some birth
control pills—medical supervision
necessary.
 Other options are IUDs or hormone
shots

Do Hormones Impact HIV Levels in
the Serum or Genital Tract?
 Exogenous progesterone enhances HIV
transmission and estrogen is protective in SIVmacaque models
 Impact of menstrual cycle is inconclusive
 Mixed data on exogenous hormones and risk of
HIV infection
 CD4 counts are lower in pregnant and postmenopausal women
QUESTIONS ABOUT PREGNANCY
AND HIV

Can I have children?

Will my pregnancy impact my HIV or does HIV affect my
pregnancy?

When is HIV transmitted during my pregnancy?

Can I breastfeed?

Do all women need HAART?

What are the effects of HAART on my baby?
 Will I or my partner get infected?
 What is the risk of HIV infection in my baby?
 How long will I live?
Pregnancy
Risk
of transmitting HIV
from mother to infant during
pregnancy is about 1 in 4 if
no treatment.
We can reduce this to less
than 1% in women who
receive:
– Prenatal and HIV care
– C-section (if necessary) and
virus load > 1000
– No breastfeeding- still has
transmission risk.
Cumulative risk of mother to child HIV transmission in the
first year of a child’s life: 35 – 40%
HIV-1 Transmission
in utero
(8-10%)
HIV-1 Transmission
intrapartum
(17-20%)
HIV-1 Transmission
postpartum
(10-15%)
Maternal Plasma HIV-1 RNA Levels at Delivery and
Antiretroviral use during Pregnancy:
Impact on Perinatal Transmission
51.4
27.8
Rates per 100
60
17.2
11.3
29.4
50
40
19
30
20
0
7.2
4.5
0
12.5
0
14.7
6.1
2.6
1.8
0
>100000
0
2.4
>3000-40000
0
1.7
Undetectable
(<400)
Maternal Plasma HIV-1 RNA
ZDV Mono (<4/94)
ZDV Mono (>4/94)
0
Multi-ART
10
0
None
0
20.4
20
HAART
Interventions for Interruption
of HIV MTCT:
Stop women from becoming infected
• VCT
• Prevention
• Testing of partners
• Decrease virus load in mothers
• Maternal ARV: pregnancy, labor, BF
• Topical microbicides during labor
•Decrease infant exposure to virus:
• Maternal treatment with ARVS
• Infant pre, peri-exposure prophylaxis
• Elective C-section
• Stop establishment of infection:
• Infant post-exposure prophylaxis
• Immunization with an HIV- vaccine
•
54
Antenatal Antiretroviral Treatment and
Perinatal Transmission in WITS, 1990-1999
Type ARV vs None
p value:
0.76
<0.01
<0.01
<0.01
U.S. Example…
300
Heterosexual contact
IDU
140
Pediatric cases
250
120
200
100
80
150
60
100
40
50
20
0
0
85
86
87
88
89
90
91
92
93
94
Quarter-Year
95
96
97
98
99
Number of Cases
Number of Cases (thousands)
160
Pregnancy: Planning

Before getting pregnant:
– Find a doctor experienced in
HIV and pregnancy
– Talk with doctor about health,
habits, mental health,
medicines, and supplements
– Start taking a prenatal vitamin
and folic acid
– Give up smoking, drinking, and
street drugs
– Develop a support network
Hepatitis C and HIV

More side effects with HIV medicines

Chance of liver failure

Chance of liver cancer

Treatment of Hepatitis C can interact
with HIV medications
Depression



60% of HIV+ women display signs of clinical
depression
Depression is treatable!
Referral to a doctor is very important to
manage symptoms
What Are Symptoms of
Depression?
 Changes
in appetite or weight
 Aches and pains
 Feelings of sadness, guilt, or low self-worth
 Irritability
 Lack of interest in activities
 Low sex drive
 Thoughts of self-harm or suicide
 Difficulty making decisions or concentrating
 Changes in sleep patterns
 Fatigue or loss of energy
Got Stress?


Stress can impact quality of life, health,
relationships, work, and mental health
Studies have shown that stress may
accelerate progression of HIV disease
Older Women Are Also at
Risk
 Misunderstandings about HIV risk in
adults
•
•
•
•
older
Lack of awareness of HIV risk factors
May be newly single
Belief that HIV only affects younger people
Health care provider belief that older adults
not sexually active
 Unprotected sexual activity
• Use of erectile dysfunction drugs contributes to increased rates of sexual
activity
• Menopause: no risk for pregnancy=no need for condom
• Vaginal dryness due to estrogen depletion led to an increased risk of HIV
acquisition
 Lack of HIV prevention education targeting older adults
Luther VP, et al. Clin Geriatr Med. 2007;23:567-583.
are
HIV and Aging




Men and women with HIV are living longer
Older people are being diagnosed with HIV
Older HIV+ patients have more medical
problems (related to age) and are on more
medications
Older patients need different support and are
frequently afraid and ashamed to share
diagnosis with family members
What about menopause?




Menopause may occur earlier in HIV+ women
Symptoms include hot flashes, irregular
bleeding, mood changes, night sweats,
painful sex
Estrogen replacement therapy may help with
some of these symptoms and prevent bone
thinning
However, hormonal therapy may increase
heart disease in some, blood clots and breast
cancer.
Living Well:
Taking Care of the Whole Woman

The benefits of good nutrition are clear:
– Well-nourished people have healthier immune
system, and are better able to fight off infections
– Many HIV+ people use food and supplements to
manage complications and side effects


Regular exercise can improve health and
strengthen immune system
Recognize and seek help for depression
“Today, we have a real opportunity to deliver like never
before . . yet still the epidemic continues to outpace
us . . . We must demand action over rhetoric and
research over ideology.”
- Helene Gayle, MD
Women and HIV:
The following is true about women living with HIV in the U.S.:
a) 10% of the people living with HIV in the U.S. are women
b) The largest share of HIV- infection in women in the U.S.
is between women ages 13- 24 years of age.
c) Fifty percent of women living with HIV in the U.S are
Black, and the remainder of infected women are Latina
or White in equal proportions.
d) Women comprise one quarter of the deaths due to HIV
in the U.S.
e) All of the above
67
Regarding HIV transmission…
Which statements are true:
a) Antiretrovirals to infected individuals confer 96%
protection against acquisition of infection.
b) The risk of a woman on antiretrovirals with an
undetectable virus load to transmit infection to her
baby is 1% or less.
c) All women with HIV should deliver by elective Csection
d) Breastfeeding is recommended for women on
antiretroviral treatment in the U.S.
e) A and B are true
68
Regarding HIV in women:
Which statements are false:
a) Women with HIV tend to become infected earlier in
life than men in Sub-Saharan Africa
b) Circumcision of men is equally protective against
HIV acquisition and HIV transmission
c) Women with HIV are at higher risk of cervical
cancer than uninfected women
d) HIV infected women have different virus load
patterns as compared to men.
e) All statements are false
69
70