Women Living With HIV: An Evolving Story

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Women Living With HIVAn Evolving Story
Carmen D. Zorrilla, MD Professor of Obstetrics
and GynecologyUniversity of Puerto Rico School
of Medicine
The International AIDS SocietyUSA
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• Only one thing defines an impossible dream the
  fear of failure
• Paulo Coelho
• The Alchemist

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Slide 3
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Changes in HIV Testing Policies and the
Implications for WomenS. Maman, E. King J
Midwifery Womens Health.  200853(3)195-201

• The CDC recommends that health care providers
  offer HIV testing to all individuals aged 13 to
  64 years as part of routine medical exams in all
  health care settings in the United States.
• Women are more likely than men to be affected by
  the efforts to expand access to HIV testing in
  health care settings because of their increased
  vulnerability to HIV and their greater contact
  with the health care system.
• The burden of partner notification will be on
  the shoulders of women who may face negative
  repercussions from their partners.
• Nevertheless, it is important to offer testing
  and early access to care.

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Women Living with HIVInitial Evaluations

• Complete physical exam
• Routine laboratories
• Confirm HIV
• Viral load, Genotype
• CD4, CD8, Lymph profile
• Check for other STIs (GC/Chlamydia, Syphilis,
  Hepatitis panel, HSV)
• Pap Smear, HPV

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Women Living with HIVInitial Management

• Evaluate social support network
• Risk reduction counseling
• Prevention strategies
• Plans for disclosure
• Reproductive choices
• Pre-conceptional counseling
• Indication for HAART

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Women's Report of Regret of HIV Disclosure to
Family, Friends and Sex Partners Julianne M.
Serovich Tiffany L. McDowell Erika L. Grafsky
AIDS Behav.  200812(2)227-231

• 73 HIV-positive women involved in a longitudinal
  study of HIV disclosure.
• Results revealed that overall, participants
  experienced little regret.
• 59 of women experienced no regret and 71 had
  regret percentages that were less than 10.
• Results indicated that all estimated odds ratios
  were not statistically significant, with the
  exception of relationship satisfaction and
  relationship to participant.

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Consistency of Initial Antiretroviral Therapy
With HIV Treatment Guidelines in a US Cohort
ofHIV-Infected Women J.Cocohoba et al J Acquir
Immune Defic Syndr 200847377-383

• Initial ART regimens given to 217 ART
  treatment-nave women in the WIHS evaluated.
  Regimens were classified as guideline consistent
  (GC), guideline not recommended (GNR), or
  unlisted.
• 53 of the women reported use of GC ART,
• 17 reported GNR ART, and
• 30 reported ART unlisted in guidelines.
• Study site, higher pretreatment CD4 cell count,
  lower HIV RNA level, and initiation before 2001
  were associated with use of GNR regimens.
• GC ART users had a higher rise in CD4 cell counts
  and more frequent undetectable HIV-1 RNA levels 2
  years after initiation compared with those GNR (P
  0.0003) or unlisted initial ART.
• Use of (GNR) was associated with a higher
  incidence of switching and poorer short-term
  immunologic and virologic outcomes

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Patterns, Predictors, and Consequences of
InitialRegimen Type among HIV-Infected
WomenReceiving Highly Active Antiretroviral
Therapy E. Golub et al, Clin Infect Dis
200846305-312

• Initial HAART regimens that include PI resulted
  in significantly higher CD4 cell counts at 2
  years among HIV-positive women compared with
  regimens based on NNRTI or triple-NRTI
• Among recent HAART initiators, one-half switched
  regimen type within 12 months of initiation, and
  nearly two-thirds switched within the first 24
  months. These high rates of switching underscore
  the complex nature of managing HIV-treatment
  regimens
• Compared with those whose initial treatment was
  protease inhibitorbased HAART, those who began
  with triple-NRTIbased regimens had significantly
  lower CD4 cell counts at 1 year (P.006) and 2
  years (P.004) after initiation NNRTI initiators
  had lower CD4 cell counts after 2 years (P.05).

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Patterns, Predictors, and Consequences of
InitialRegimen Type among HIV-Infected
WomenReceiving Highly Active Antiretroviral
Therapy E. Golub et al, Clin Infect Dis
200846305-312
Figure 1. Calendar time trends in initial regimen
type among 1673 participants in the Womens
Interagency HIV Study. The x-axis indicates
January and July as the midpoints of the
calendar-based study-visit windows.
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Association Between Living With Children
andAdherence to Highly Active Antiretroviral
Therapyin the WIHS D. Merenstein et al,
Pediatrics 2008121e787-e793

• Having children living at home is associated with
  reduced adherence to highly active antiretroviral
  therapy (HAART) among women with HIV (n1,366)
• Women who had two or more children in the
  household had 72 adherence compared with 76
  among women with one child and 78 among those
  with no children.
• In multivariate analysis adjusting for
  demographics, illicit drug use, quality of life
  score, health insurance status, and CD4 cell
  count, the authors estimate a 6 decrease in the
  odds of adherence with each additional child as
  compared with childless women (p for trend
  0.055).

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Children Impact Womens Adherence

• Adherence to HAART is inversely associated with
  number of children living in household (n1,366)
• 6 decrease in odds of adherence with each
  additional child

Merenstein, Pediatrics 2008e787-793
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Occurrence of Vaginal Infections Among
HIV-Infected and High-Risk HIV-Uninfected Women
Longitudinal Findings of the WIHSH Watts et al J
Acquir Immune Defic Syndr.  200643(2)161-168

• 2,056 HIV and 554 HIV- women were evaluated
  semiannually from 1994 until March 2003.
• BV was diagnosed by Gram stain, TV by wet mount,
  and YV by symptoms , hyphae or positive culture.
• Over time, rates of BV and TV decreased
  significantly in both groups, whereas rates of YV
  declined only among HIV-infected women. Risk of
  BV was not associated with HIV status, whereas
  HIV-infected women had a lower risk of TV.
• HAART use was associated with decreased risk of
  all 3 infections.
• Conclusions Declines in BV, TV, and YV represent
  decreased morbidity for HIV-infected women and,
  potentially, decreased risk of transmission of
  HIV, because each has been associated with
  increased genital detection of HIV.

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HPV

• More than 100 types of HPV exist more than 30
  types can infect the genital area. The majority
  of HPV infections are asymptomatic and usually
  self-limited.
• Genital HPV infection occurs more frequently than
  visible genital warts among both men and women
  and cervical cell changes among women.
• Genital warts are usually associated with HPV
  types 6 or 11. Other HPV types that infect the
  anogenital region (e.g., high-risk HPV types 16,
  18, 31, 33, and 35) are strongly associated with
  cervical neoplasia.
• Persistent infection with high-risk types of HPV
  is the most important risk factor for cervical
  neoplasia
• Cervical cancer is the second most common cause
  of cancer in women in the world.

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HIV and HPV

• Although ART has dramatically altered HIV natural
  history, its impact on HPV and HPV-associated
  neoplasia is less clear. Some studies but not all
  have found reduced persistence/progression of CIN
  with use of ART.
• Most studies of cancer incidence have failed to
  show decreases in either cervical or anal cancer
  incidence since the widespread introduction of
  ART.
• With ART having limited or no impact on
  HPV-associated cancers, and HIV-seropositive
  individuals living longer, HIV-seropositive women
  and men will increasingly be entering middle age,
  when the incidence of cervical and other
  HPV-associated cancers typically increases.
• Guidelines for Prevention and Treatment of
  Opportunistic Infections in HIV-Infected Adults
  and Adolescents - June 18, 2008
  (www.aidsinfo.nih.gov)

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Question
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Cervical cancer screening guidelines
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HPV testing and HIV

• HPV testing may be used in the management of
  HIV-seronegative women with a cytologic diagnosis
  of ASC-US. This has been recommended for similar
  use in HIV women in American Society for
  Colposcopy and Cervical Pathology (ASCCP)
  guidelines but at present there are insufficient
  data to support this.
• Likewise, unlike for HIV-seronegative women,
  there are no current recommendations for the use
  of HPV testing for triage of HIV-seropositive
  women over the age of 30 years with normal
  cervical cytology (e.g., to less or more frequent
  Pap tests based on a hybrid capture test) or in
  follow-up of CIN after treatment.
• The Pap test should be obtained twice during the
  first year after diagnosis of HIV infection and,
  if the results are normal, annually thereafter.
• Guidelines for Prevention and Treatment of
  Opportunistic Infections in HIV-Infected Adults
  and Adolescents - June 18, 2008
  (www.aidsinfo.nih.gov)

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HPV Treatment

• In the absence of genital warts or cervical SIL,
  treatment is not recommended for subclinical
  genital HPV infection, whether it is diagnosed by
  colposcopy, biopsy, acetic acid application, or
  through the detection of HPV by laboratory tests.
  
• Strategies to treat genital warts or cervical
  dysplasia are
• Trichloroacetic acid (TCA) or bichloroacetic acid
  (BCA) (8090)
• Cryotherapy (liquid nitrogen or cryoprobe)
• Podophyllotoxin, e.g., podofilox (0.5 solution
  or gel)
• Imiquimod (5 cream) and
• surgical treatments
• Guidelines for Prevention and Treatment of
  Opportunistic Infections in HIV-Infected Adults
  and Adolescents - June 18, 2008
  (www.aidsinfo.nih.gov)

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• The Search always starts with beginners luck and
  ends with the Conquerors test
• Paulo Coelho
• The Alchemist

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HPV Vaccine

• On June 8, 2006, the FDA licensed the first
  vaccine developed to prevent cervical cancer and
  other diseases in females caused by certain types
  of genital human papillomavirus (HPV).
• The quadrivalent vaccine protects against four
  HPV types (6,11,16, 18), which are responsible
  for 70 of cervical cancers and 90 of genital
  warts. On June 29, 2006, the Advisory Committee
  on Immunization Practices (ACIP ) voted to
  recommend use of this vaccine in females, ages
  9-26 years.

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HPV vaccine efficacy

• The efficacy of this vaccine has mainly been
  studied in young women (16-26 years of age) who
  previously had not been exposed to any of the
  four HPV types in the vaccine.
• These clinical trials have demonstrated 100
  efficacy in preventing cervical pre-cancers
  caused by the targeted HPV types, and nearly 100
  efficacy in preventing vulvar and vaginal
  pre-cancers and genital warts caused by the
  targeted HPV types.
• The vaccine has no therapeutic effect on
  HPV-related disease. If a girl or woman is
  already infected with one of the HPV types in the
  vaccine, the vaccine will not prevent disease
  from that type.

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Preconception Counseling and care for women
living with HIV PHS Perinatal Guidelines July 8,
2008

• The Centers for Disease Control and Prevention
  (CDC), the American College of Obstetrics and
  Gynecology (ACOG), and other national
  organizations recommend offering all women of
  childbearing age the opportunity to receive
  preconception counseling and care as. a component
  of routine primary medical care

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Live birth patterns among HIV-infected women
before and after the availability of HAART A.
Sharma, Minkoff et al Am J Obstet Gynecol
2007196541

• Among HIV-infected women, the HAART era live
  birth rate was 150 higher than in the pre-HAART
  era (P.001) vs. a 5 increase among
  HIV-uninfected women.
• Mean age of the first group was 29 years and mean
  age of the second group was 33 years
• The rate of increase in live birth rate was
  higher for women 35 years old (vs. younger than
  25 years, P.02), and with more than a high
  school education (vs. less than high school,
  P.05).
• The availability of effective therapeutic
  interventions has had a profound impact on
  child-bearing among HIV-infected women.

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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 (gt10 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, methadone)

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Fertility Evaluation physical exam

• Body habitus (metabolic syndrome GDM, PCO)
• BMI (lt18 and gt27 related to decreased fertility)
• Hirsutism (Poly Cystic Ovaries-PCO)
• Pelvic exam with signs of PID

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Fertility evaluation Labs

• Preconception counseling labs
• Serum Prolactin and TSH
• Tubal patency by HSG or laparoscopy
• Ovarian reserve day 3 FSH (gt10-15 IU/L) and
  estradiol (gt75-80 pg/ml)
• Ovulation tests
• Progesterone gt3ng/ml on day 21 (1 week before
  menses)
• Positive LH (commercial ovulation kits) or
• BBT chart

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International AIDS Society Conference on HIV
Pathogenesis, Treatment and PreventionPietro
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 had conceived,
  after 10 attempts, 15 were pregnant.
• All the women in the study tested negative for
  HIV, 3 months after the last exposure.

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Question
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Pregnancy Considerations
Slide 30

• 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

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Modes of Transmission
Intrauterine
Labor and Delivery
Breastfeeding
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Key issues when treating pregnant women

• Drugs that cross the placenta and reach fetal
  circulation (such as NRTIs and NNRTIs)
• Drugs that do not (or very limited) cross the
  placenta (PIs)
• Know the PK profile of the drugs
• Labor and delivery treatment (if labor is
  prolonged)
• Neonatal ART and infant formula

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Issues with antiretroviral use in pregnancy

• Need for antiviral drug resistance testing
• Choice of drugs PI vs non-PI
• Missing pregnancy PK data on new drugs
  Amprenavir (Agenerase), Atazanavir (Reyataz),
  Darunavir (Prezizta), Fosamprenavir (Lexiva),
  Tipranavir (Aptivus), Maraviroc (Selzentry),
  Raltegravir (Isentress)
• Nelfinavir contamination (over)
• go to www.aidsinfo.nih.gov

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Slide 34
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Perinatal HIV Transmission Puerto Rico and CEMI
1990 - 2006

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Question