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Contraception
       update and HIV issues




RHRU
Pregnancies: Unintended vs.
           Intended
Intended
  51%                     Unintended
                            49%:

                           Unintended
                         births (22.5%)




               Elective abortions
                    (26.5%)
Contraceptive Choices
•   Oral contraceptives: combined, progestin-only
•   Long-acting
    –   Injectable
    –   Implants
    –   IUD: copper T, progestin-only
•   Barrier contraceptives
•   Spermicides
•   Natural family planning
•   Emergency contraceptives
•   Female/male sterilization
Current Trends in Contraception
• Developing new delivery systems
• Increasing access to a full range of
  options
• Emphasizing better compliance:
  Longer acting hormonal contraceptives
  that do not require daily attention.
• Widening use of emergency
  contraception
Case for Long-Acting and
   Permanent Methods (LAPMs)
• Convenient for users and effectively prevent
  pregnancy
• Cost effective for programs over time - result in
  substantial cost savings for governments and
  attainment of health goals
• Long-acting, reversible methods fulfill the need
  for healthier timing and spacing of pregnancies
• Permanent (and long acting) methods would
  meet the need of individuals and couples who
  want no more children.
• Are between 3 & 60 times more effective than
  most short-acting methods
Progestin-Only Injectables
• The new, revised WHO guidance (April 2008) states that
  reinjections of DMPA can be given up to four weeks late
  without otherwise ruling out pregnancy.
• The data came from a 2007 prospective study in
  Thailand, Uganda, and Zimbabwe. Women followed for
  up to 24 months. The 2,290 DMPA users contributed
  13,608 DMPA injection intervals.
• Implications for practice:
   – Providers need not and should not turn away clients who are late
     for DMPA reinjection.
   – If a client is up to four weeks late, her provider should give her
     the injection.
   – If a client is more than fours weeks late, rule out pregnancy
     before giving injection.
   – If the injection cannot be given immediately, the provider should
     offer back-up methods of contraception. DMPA injections should
     still be scheduled three months apart.
• NET-EN grace period still 2 weeks
Progestin-Only Injectables: Bone
            density
• Summary:
  – New studies contribute further evidence that bone
    mineral density decreases during use of progestin
    only injectable contraceptives but increases again
    when use stops.
  – Studies need to look at possible long-term effects for
    adolescents and women entering menopause.
• Implications for practice:
  – The new evidence supports WHO’s guidance that the
    loss of bone mineral density does not limit use of
    progestin-only injectables.
  – Providers and users of progestin-only injectables who
    are adolescents or over age 45 may want to consider
    the advantages of using injectables and the
    theoretical risks of their effect on bone mineral
    density.
New methods
Newer pills
• Yasmin:
   – COC that contains a synthetic progesterone
     (drospirenone) with antiandrogenic and
     antimineralocorticosteroid properties.
   – Less water retention than other COCs, less negative
     emotional affect, and less appetite increase after six
     months' use.
   – Note contains spironolactone, a potassium-sparing
     diuretic, certain restrictions.
• Cerazette:
   – POP (75mcg of desogestrel daily) designed to inhibit
     ovulation.
   – 12 hour pill taking safety margin
   – Bleeding pattern more variable than with Microval,
     but greater tendency towards infrequent bleeding
     and amenorrhoea by the end of the first year.
Monthly Injection: Lunelle/
                Cycloprovera
•   Intramuscular injection q 28-30 days
•Combined injectable (25mg Medroxyprogesterone
acetate / 5 mg estradiol cypionate)
•   Rapid return to fertility after discontinuation
•   Adverse events are similar to COCs
•   Excellent cycle control
Contraceptive Implant: Implanon

• Single implant rod (4 cm in
  length and 2 mm in diameter)
  made of ethylene vinyl acetate
• Contains 68 mg of etonogestrel
  (3-keto-desogestrel), the active
  metabolite of desogestrel
• Effective for 3 years
   – Inhibits ovulation during the
     entire treatment period
Levonorgestrel Intrauterine System:
             Mirena

• Releases 20 µg of
  levonorgestrel per 24 hrs
• Duration: 5 years
• Packaged with sterile
  inserter
• High efficacy
   – Pearl Index of 0.1
Mirena Mechanisms of Action
– Cervical mucus is
 thickened
– Sperm motility and
 function inhibited
– Endometrium suppressed
– Weak foreign body
 reaction induced
– Ovulation inhibited (in
 some cycles)
Vaginal Ring: NuvaRing
                • The NuvaRing releases 15 µg
                  of ethinyl estradiol and 120 µg
         4 mm     of etonogestrel daily for 21
                  days
                • Begin the contraceptive
54 mm             cycle when pregnancy can
                  be excluded
                • The vaginal ring is flexible
                  and easy to insert and
                  remove
                • The ring is worn for 3 weeks
                  and discarded, and a new
                  ring is inserted 1 week later
                  (28 day cycle)
Rationale for Vaginally Administered
            Contraception
• Easily inserted by the user
• A monthly method
  • No need for daily intake
• Continuous release with constant serum
  hormone levels
• Lowest EE dose
• Avoids gastrointestinal interference with
  absorption
• Avoids hepatic first-pass metabolism of the
  progestin
Contraceptive Patch: Ortho Evra

       • Patch contains 6 mg norelgestromin
         and 0.75 mg ethinyl estradiol
       • Delivers continuous systemic low
         doses of hormones daily
         –   150 µg norelgestromin (NGMN)
         –   20 µg ethinyl estradiol (EE)
       • Bypasses GI tract
       • Ease of application and removal
       • Overall annual probability of
         pregnancy in patch users was
         reported at 0.8%
Transdermal Contraceptive System
 • Ortho Evra/Evra (20-µg ethinyl estradiol/
    150-µg norelgestromin)
    – 3 patch system
       • Apply 1 patch a week for 3 weeks
       • Apply each patch same day of the week
    – 1 week is patch-free
 Patch #1   Patch #2    Patch #3   Patch-free     Start next cycle
               28-day cycle                        28-day cycle



Week        Week       Week        Week         Week
 1           2          3           4            5
Emergency contraception
• Progesterone only versus Yuzpe regimen
• Single dose versus two interval doses
• Extension of 72 hour limit to 5 days
• Cu-IUD

• Three new studies looking at the mechanism of
  action of levonorgestrel emergency contraceptive
  pills (LNG-ECPs) contributed further evidence that
  LNG-ECPs work by primarily preventing ovulation.
• Implications for practice: Clients need thorough
  counseling on how and when to take ECPs, and to
  correct misunderstandings about when pregnancy is
  most likely.
Mechanical Barrier Methods

•   Male and female condoms
•   Male (“ez-on”) and female (bikini) condoms
•   Disposable diaphragms
•   Lea’s shield (silicone)
•   SILCS intravaginal barrier (silicone)
•   Femcap (silicone)
•   BufferGel cup
•   Microbicides
Female condom

• New, cheaper more
  acceptable female
  condoms being
  evaluated
Modelling estimates that
perfect use of FC among
women who have
intercourse 2x week with
infected male might
reduce annual risk of
acquiring HIV by > 90%
Male Contraception

• Traditional: condoms, vasectomy.
• 1990s: Weekly injections of testosterone
  enanthate to induce azospermia. Side effects:
  weight gain, acne and serum lipid changes.
• More recent research: androgen-progestogen
  combinations that suppress gonadotrophins.
• Gossypol (derivative of cottonseed oil).
• Lonidamine: reduces normal sperm
  production.
• Epidydymal agents.
Sterilisation
• Vasectomy more effective of the 2 methods (failure rate
  of 1 in 10,000) cf with female sterilisation (1 in 200
  lifetime risk of failure).
• Female sterilisation is effective immediately, whereas
  male sterilisation requires a “washout” period of about 3
  months (2 azospermic semen analysis at least 4 weeks
  apart confirms success).
• Risks of sterilisation
    – Female:
        • Risk of operative complications
        • Effect on long-term health – Regret 6%,
          uncomplicated female sterilisation has no long
          term effects on menstruation or the genital tract
    – Male:
        • Risk of operative complications
        • Effect on long-term health
Transcervical sterilization
• Fallopian tubes approached through cervix
  instead of abdominal incision.
• Essure permanent birth control system: coil
  mechanism.
• Quinacrine-induced occlusion: 2 doses of
  quinacrine pellets, one month apart, between
  day 7 and 10 of the menstrual cycle.
  ?carcinogenicity
• Erythromycin (animal studies).
• Intratubal Ligation device and two step
  Adiana system
Checklists
HIV and contraception
Who is getting infected
HIV and Maternal/infant mortality
HIV is the single largest
cause of maternal and
infant death in several
parts of sub-Saharan
Africa and has reversed
previous gains made in
some countries.
Pregnancy may increase
HIV acquisition.
Contraception and HIV:
               What to consider

   Women at risk                    Women infected
     for HIV                          with HIV




                                            Disease     Drug
Prevention   Acquisition   Infectiousness               interactions
                                          progression
HIV acquisition
• Large prospective cohort study, funded by the U.S.
  NICHD, was conducted by FHI and collaborating
  institutions among some 6,100 family planning clients in
  Uganda, Zimbabwe, and Thailand.
• Involved HIV-negative, 18- to 35-year-old women in
  three exposure groups of roughly equal size: combined
  oral contraceptive (COC) users, DMPA users, and
  women not using hormonal contraception.
• Designed specifically to evaluate the relationship
  between the use of low-dose COCs or DMPA and HIV
  acquisition
• Four-year study found no overall association between
  the use of either combined oral contraceptive (COC) pills
  or depot-medroxyprogesterone acetate (DMPA) and HIV
  acquisition.
HIV acquisition
• Women were tested for HIV infection every 12
  weeks until they became infected or had been
  followed for 15 to 24 months (overall retention
  rate of 91 percent).
• Strongest study to date exploring this issue.
  However, not a randomized controlled trial,
  therefore cannot provide evidence to establish a
  direct cause-effect relationship.
• Morrison C, Richardson B, Mmiro F, et al.
  Hormonal contraception and the risk of HIV
  acquisition. AIDS 2007;21(1):85-95.
HIV Acquisition: For Most, No Additional
  Risk With Hormonal Methods, IUDs
• A study in South Africa (Palesa Study) found
  that the numbers of new cases of HIV were
  similar among women using either progestin-
  only injectables or COCs and among women not
  using any hormonal method, after adjusting for
  differences in sexual risk behaviors and the
  presence of STIs.
• Limited evidence from other studies also
  suggest that women using the copper-bearing
  IUD are not at greater risk of acquiring HIV.
                                  Kleinschimdt 2005
HIV Acquisition: High risk groups

• Among populations at high risk of HIV exposure,
  such as sex workers, some studies (Mombasa
  study) find that hormonal contraception
  increases the risk of HIV acquisition. For
  example, sex workers in Kenya using COCs or
  DMPA had a 1.5 times and 1.8 times greater
  risk, respectively, of acquiring HIV than sex
  workers who were not using these methods,
  after adjusting for condom use and number of
  sexual partners.
                                   Lavreys 2005
HIV infectivity: Limited and Unclear
     Evidence on Viral Shedding
• Unknown whether HC use by HIV-infected women
  increases their risk of infecting sexual partners.
• Limited studies: Only 2 studies have been
  prospective, and the results of cross-sectional
  studies of HIV shedding from the genital tract are
  conflicting, perhaps due to relatively small study
  samples.
HIV infectivity: Limited and Unclear
   Evidence on Viral Shedding
• How to determine a woman's HIV infectiousness
  also is unclear.
   – Amount of HIV genital shedding necessary to
     increase infectiousness is unknown.
   – Questions remain about the best technique
     for detecting HIV in genital tract secretions.
• No consensus exists on what indicators best
  reflect the risk of HIV infectivity.
HIV infectivity
• 213 HIV-infected family planning clients in Mombasa, Kenya
  (2004)
   – Only prospective study of the direct effect of hormonal
     contraceptive use on genital tract shedding of HIV
   – Detected a significant but modest increase in cervical
     shedding of HIV-1 DNA after initiation of hormonal
     contraceptives. Not noted for separate groups.
• Increase in cervical shedding of HIV-1 DNA associated with
  hormonal contraceptive use overall was not accompanied by
  an increase in cervical shedding of HIV-1 RNA.
   – Possible explanation that HC use attracts infected cells to
     the genital mucosa (evidenced by increased HIV-1 DNA)
     but does not increase local viral replication in the mucosa
     (which increased HIV-1 RNA would reflect).
HIV infectivity
• Another prospective study, conducted in 2005 among
  967 U.S. women (654 of whom were HIV-infected),
  found that:
   – Progesterone-based contraceptives appeared to raise
     the number of cervicovaginal inflammatory cells,
     assumed to be associated with increased HIV-1 viral
     load in genital secretions.
   – Limitation: small number of participants using
     progesterone contraception - the analysis had little
     statistical power.
• IUDs do not appear to increase the infectiousness of
  women with HIV. The two studies that have looked at the
  prevalence of HIV-infected cells in the cervix found no
  greater shedding due to IUD use.
HIV progression: Could Hormonal
   Methods Speed Up Disease?
• Does the use of HC during the early or later stages of
  HIV infection affect disease progression?
• Only evidence so far that HC use might affect HIV
  disease progression comes from a prospective study
  conducted among 161 sex workers in Mombasa, Kenya.
  This evidence suggests that using HC at the time of
  infection — before women know that they are infected —
  may accelerate HIV-related deterioration of the immune
  system and thus speed the natural course of the
  infection.
• Evidence of risk considered insufficient to warrant any
  restrictions on hormonal contraceptive use by women
  with HIV/AIDS or women at high risk of infection.
Viral set point and diversity
• In Kenya study, median viral set point was significantly
  higher among women using the DMPA at the estimated time
  of HIV infection than among women using no hormonal
  contraception at that time. Persisted during follow-up
  (median of 34 months). However, continuing use of DMPA
  did not appear to further increase viral load.
• Overall, use of oral contraceptive pills was not associated
  with higher viral set points. But in subset of 156 HIV-infected
  sex workers use of either OCs or DMPA at the time of HIV
  infection was associated with acquiring genetically diverse
  virus populations from one partner.
• Limited evidence suggests any impact HC use may have on
  HIV disease progression occurs during the early stages of
  the infection.
Drug Interactions: Do ARVs Reduce
Effectiveness of LD Hormonal Contraceptives?
• Limited evidence suggests certain ARVs could alter
  blood levels of contraceptive hormones in women
  using low dose OCs.
• Two small studies reported that the ARVs
  nevirapine and ritonavir could lower both estrogen
  and progestin levels enough to increase risk of
  contraceptive failure. Both studies evaluated the
  effect of just a single dose of COC. No information
  is available on women taking a pill every day. Thus,
  it is not clear whether or how much contraceptive
  effectiveness would be reduced.
• Despite the theoretical concern about contraceptive
  effectiveness, women taking ARVs still generally
  can use COCs.
Drug Interactions: Do ARVs Reduce
Effectiveness of LD Hormonal Contraceptives?
• The few studies available find that ARVs have
  little or no effect on hormone levels in DMPA
  users with HIV. Providers can emphasize
  returning on time for the next injection. This will
  help to ensure that hormone levels remain high
  enough to prevent pregnancy. .
• Hormonal contraceptives do not appear to
  reduce the effectiveness of ARVs.
Contraceptive Options for HIV-infected
              Women
• Women with HIV have a right to decide whether
  they want to become pregnant and bear
  children.
• If an HIV-infected woman chooses not to have
  children, or wants to space her family, she
  should be able to make informed, voluntary
  decisions about contraception and then receive
  her method of choice. Such use of contraception
  by HIV-infected women is an important way to
  reduce HIV-positive births.
• HIV-infected women can use most contraceptive
  methods safely.
Contraceptive Options for HIV-infected
              Women
• Need to weigh the advantages and
  disadvantages of various methods and consider
  the effects of each method on her own health,
  risk of infecting others with HIV, and response to
  HIV/AIDS treatment.
• Counsellors should help each HIV-infected
  woman assess her contraceptive needs, review
  all options available to her, and determine
  whether she and her partner will be able to use
  a particular method or combination of methods
  safely, correctly, and consistently.
Contraception and HIV:
       Options




     Barrier methods
Condom Effectiveness
       Contraceptive Contraceptive          STI/HIV
       effectiveness effectiveness       effectiveness
       Consistent and    Typical use
        correct use


Male   97%              86%            Proven to protect
Condom                                 against STI/HIV
                                       Reduces HIV
                                       incidence by 80-
                                       97% when used
                                       correctly and
                                       consistently
Female 95%              79%            Effective in vitro.
Condom                                 Limited data on
                                       efficacy in real use
Condoms
• Condoms should be promoted, together with an
  additional form of contraception, as an ideal method of
  contraception.
• This reduces the transmission of HIV to her current and
  possible future partners if they are at risk of HIV
  infection. If they are already infected the use of condoms
  is still advised, as in addition to the prevention of
  conception, it prevents the transmission of sexually
  transmitted infections and prevents infection with new
  strains of HIV
• The effect of condoms is not
  altered by the use of ART.
Other barrier methods
• Barrier methods other than condoms offer only modest
  protection against pregnancy and are generally not
  recommended for women with HIV.
• Frequent use of spermicides containing nonoxynol-9 (N-
  9) may increase the risk of reinfection with other strains
  of HIV because N-9 can disrupt the lining of the vagina,
  making it more vulnerable to infection. Studies have also
  shown that N-9 offers no protection against STIs.
• Diaphragms and cervical caps are not recommended for
  women with HIV or AIDS and women at high risk of HIV
  infection because they are usually used with spermicides
  containing N-9.
• Recent study (Mira trial) showed no increase HIV
  protection with diaphragm use. (Lancet July 2007)
Contraception and HIV:
       Options




   ‘Modern’ methods of
      Contraception
Hormonal methods
• The World Health Organization (WHO) recommends that
  HIV-infected women can safely use hormonal
  contraceptives — including combined oral contraceptives
  (COCs), the injectables depot-medroxyprogesterone
  acetate (DMPA) and norethisterone enanthate (NET-
  EN), and implants such as Norplant.
• Questions remain about the effects of hormonal
  contraception on a woman's HIV infectiousness and
  disease progression and about the consequences of
  interactions between these methods and antiretroviral
  (ARV) drugs.
IUDs
• In 2004 the World Health Organization updated its
  guidance, based on recent research, and now advises
  that women with HIV can generally start using either a
  copper-bearing IUD or a hormonal IUD. Specific
  guidance includes:
   – Women with HIV who do not have AIDS can generally
     have copper-bearing and hormonal IUDs inserted.
   – Women with AIDS who are on ARVs and are clinically well
     generally also can have the IUD inserted.
   – IUD insertion usually is not recommended for women who
     have AIDS and are not on ARVs, however. The IUD also is
     not usually recommended for women who are using ARVs
     but are not clinically well.
   – If an IUD user becomes infected with HIV or if an IUD user
     with HIV develops AIDS, the IUD generally does not need
     to be removed. She should be monitored for signs of PID.
Sterilisation
• Offers couples a safe, highly effective, permanent
  method of contraception. May be a good option for HIV-
  positive women and their partners who have decided to
  forgo or end childbearing, and it raises no particular
  health concerns for HIV-infected women.
• HIV-discordant couples in which the man is HIV-negative
  and the woman is HIV-positive may want to consider
  male sterilization because it does not depend on the
  woman's health.
• Studies show a reduction in consistent condom use in
  couples after one partner has undergone sterilization.
  Couples should be counseled about the importance of
  using condoms if they might be at risk of HIV infection.
• Avoid coercion.
Female Sterilization and
          Vasectomy are Safe
• For people with AIDS, special arrangements should be
  made to perform the procedure in a setting with a
  qualified provider, with appropriate equipment and
  support.
• Women or men with acute AIDS-related illness may
  have to wait until their condition improves before
  undergoing the procedure
Emergency contraception
• Should be made available for all women who use barrier
  contraception only.
• Classical contra-indications for hormonal contraception
  such as previous ectopic pregnancy, cardiovascular
  disease, migraine, liver disease and breastfeeding are
  not considered contraindications to emergency
  contraception use.
• The use of antiretroviral therapy should not preclude the
  use of emergency contraception and the favoured
  method should be progesterone based morning after pill
  for women who are on ART.
Other methods
• Lactational amenorrhoea method:
  – Women who are infected with HIV or who have AIDS and
    choose to breastfeed their infant can use LAM.
  – Exclusive breastfeeding for the first six months of a baby’s
    life is the safer breastfeeding pattern to minimize the risk
    of HIV transmission through breastmilk.
  – If a woman’s monthly bleeding returns before six months,
    she will need another contraceptive method while
    continuing to breastfeed exclusively.
  – Women with HIV and their health care providers need to
    consider the infant feeding options available and to weigh
    their various risks and consequences.
Summary

• Increasing number of women will be aware
  of their HIV status
• Providers need to be aware of new data to
  advise HIV infected women regarding their
  options to prevent unwanted pregnancies
Contraception and HIV acquisition
Method &                Strength of evidence Comment
HIV acquisition         of interaction


Injectable progestins   -                  General population
                        +                  Higher risk groups
                                           (SWs), younger age
                                           group, HSV2 negative

COCs                    -                  General population
                        +                  Higher risk groups
                                           (SWs), younger age
                                           group
IUDs                    -                  General population
Contraception and HIV transmission
Method &                Strength of   Comment
HIV transmission        evidence


Injectable progestins   -             General population
                        ?+            Higher risk groups (SWs),


COCs                    -             General population
                        ?+            Higher risk groups (SWs)


IUDs                    -             General population
Contraception and HIV progression
Method &                Strength of   Comment
HIV progression         evidence

Injectable progestins   -             General population
                        +             Worse prognostic disease in
                                      higher risk groups (SWs).
                                      Worse disease progression?
                                      (from RCT with IUDs)
COCs                    +             Worse prognostic disease in
                                      higher risk groups (SWs).
                                      Worse disease progression?
                                      (from RCT with IUDs)
IUDs                    -             IUD use appears safe in HIV+ve
                                      women.
Thank you

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Contraception And Hiv

  • 1. Contraception update and HIV issues RHRU
  • 2. Pregnancies: Unintended vs. Intended Intended 51% Unintended 49%: Unintended births (22.5%) Elective abortions (26.5%)
  • 3. Contraceptive Choices • Oral contraceptives: combined, progestin-only • Long-acting – Injectable – Implants – IUD: copper T, progestin-only • Barrier contraceptives • Spermicides • Natural family planning • Emergency contraceptives • Female/male sterilization
  • 4. Current Trends in Contraception • Developing new delivery systems • Increasing access to a full range of options • Emphasizing better compliance: Longer acting hormonal contraceptives that do not require daily attention. • Widening use of emergency contraception
  • 5. Case for Long-Acting and Permanent Methods (LAPMs) • Convenient for users and effectively prevent pregnancy • Cost effective for programs over time - result in substantial cost savings for governments and attainment of health goals • Long-acting, reversible methods fulfill the need for healthier timing and spacing of pregnancies • Permanent (and long acting) methods would meet the need of individuals and couples who want no more children. • Are between 3 & 60 times more effective than most short-acting methods
  • 6. Progestin-Only Injectables • The new, revised WHO guidance (April 2008) states that reinjections of DMPA can be given up to four weeks late without otherwise ruling out pregnancy. • The data came from a 2007 prospective study in Thailand, Uganda, and Zimbabwe. Women followed for up to 24 months. The 2,290 DMPA users contributed 13,608 DMPA injection intervals. • Implications for practice: – Providers need not and should not turn away clients who are late for DMPA reinjection. – If a client is up to four weeks late, her provider should give her the injection. – If a client is more than fours weeks late, rule out pregnancy before giving injection. – If the injection cannot be given immediately, the provider should offer back-up methods of contraception. DMPA injections should still be scheduled three months apart. • NET-EN grace period still 2 weeks
  • 7. Progestin-Only Injectables: Bone density • Summary: – New studies contribute further evidence that bone mineral density decreases during use of progestin only injectable contraceptives but increases again when use stops. – Studies need to look at possible long-term effects for adolescents and women entering menopause. • Implications for practice: – The new evidence supports WHO’s guidance that the loss of bone mineral density does not limit use of progestin-only injectables. – Providers and users of progestin-only injectables who are adolescents or over age 45 may want to consider the advantages of using injectables and the theoretical risks of their effect on bone mineral density.
  • 9. Newer pills • Yasmin: – COC that contains a synthetic progesterone (drospirenone) with antiandrogenic and antimineralocorticosteroid properties. – Less water retention than other COCs, less negative emotional affect, and less appetite increase after six months' use. – Note contains spironolactone, a potassium-sparing diuretic, certain restrictions. • Cerazette: – POP (75mcg of desogestrel daily) designed to inhibit ovulation. – 12 hour pill taking safety margin – Bleeding pattern more variable than with Microval, but greater tendency towards infrequent bleeding and amenorrhoea by the end of the first year.
  • 10. Monthly Injection: Lunelle/ Cycloprovera • Intramuscular injection q 28-30 days •Combined injectable (25mg Medroxyprogesterone acetate / 5 mg estradiol cypionate) • Rapid return to fertility after discontinuation • Adverse events are similar to COCs • Excellent cycle control
  • 11. Contraceptive Implant: Implanon • Single implant rod (4 cm in length and 2 mm in diameter) made of ethylene vinyl acetate • Contains 68 mg of etonogestrel (3-keto-desogestrel), the active metabolite of desogestrel • Effective for 3 years – Inhibits ovulation during the entire treatment period
  • 12. Levonorgestrel Intrauterine System: Mirena • Releases 20 µg of levonorgestrel per 24 hrs • Duration: 5 years • Packaged with sterile inserter • High efficacy – Pearl Index of 0.1
  • 13. Mirena Mechanisms of Action – Cervical mucus is thickened – Sperm motility and function inhibited – Endometrium suppressed – Weak foreign body reaction induced – Ovulation inhibited (in some cycles)
  • 14. Vaginal Ring: NuvaRing • The NuvaRing releases 15 µg of ethinyl estradiol and 120 µg 4 mm of etonogestrel daily for 21 days • Begin the contraceptive 54 mm cycle when pregnancy can be excluded • The vaginal ring is flexible and easy to insert and remove • The ring is worn for 3 weeks and discarded, and a new ring is inserted 1 week later (28 day cycle)
  • 15. Rationale for Vaginally Administered Contraception • Easily inserted by the user • A monthly method • No need for daily intake • Continuous release with constant serum hormone levels • Lowest EE dose • Avoids gastrointestinal interference with absorption • Avoids hepatic first-pass metabolism of the progestin
  • 16. Contraceptive Patch: Ortho Evra • Patch contains 6 mg norelgestromin and 0.75 mg ethinyl estradiol • Delivers continuous systemic low doses of hormones daily – 150 µg norelgestromin (NGMN) – 20 µg ethinyl estradiol (EE) • Bypasses GI tract • Ease of application and removal • Overall annual probability of pregnancy in patch users was reported at 0.8%
  • 17. Transdermal Contraceptive System • Ortho Evra/Evra (20-µg ethinyl estradiol/ 150-µg norelgestromin) – 3 patch system • Apply 1 patch a week for 3 weeks • Apply each patch same day of the week – 1 week is patch-free Patch #1 Patch #2 Patch #3 Patch-free Start next cycle 28-day cycle 28-day cycle Week Week Week Week Week 1 2 3 4 5
  • 18. Emergency contraception • Progesterone only versus Yuzpe regimen • Single dose versus two interval doses • Extension of 72 hour limit to 5 days • Cu-IUD • Three new studies looking at the mechanism of action of levonorgestrel emergency contraceptive pills (LNG-ECPs) contributed further evidence that LNG-ECPs work by primarily preventing ovulation. • Implications for practice: Clients need thorough counseling on how and when to take ECPs, and to correct misunderstandings about when pregnancy is most likely.
  • 19. Mechanical Barrier Methods • Male and female condoms • Male (“ez-on”) and female (bikini) condoms • Disposable diaphragms • Lea’s shield (silicone) • SILCS intravaginal barrier (silicone) • Femcap (silicone) • BufferGel cup • Microbicides
  • 20.
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  • 24. Female condom • New, cheaper more acceptable female condoms being evaluated Modelling estimates that perfect use of FC among women who have intercourse 2x week with infected male might reduce annual risk of acquiring HIV by > 90%
  • 25. Male Contraception • Traditional: condoms, vasectomy. • 1990s: Weekly injections of testosterone enanthate to induce azospermia. Side effects: weight gain, acne and serum lipid changes. • More recent research: androgen-progestogen combinations that suppress gonadotrophins. • Gossypol (derivative of cottonseed oil). • Lonidamine: reduces normal sperm production. • Epidydymal agents.
  • 26. Sterilisation • Vasectomy more effective of the 2 methods (failure rate of 1 in 10,000) cf with female sterilisation (1 in 200 lifetime risk of failure). • Female sterilisation is effective immediately, whereas male sterilisation requires a “washout” period of about 3 months (2 azospermic semen analysis at least 4 weeks apart confirms success). • Risks of sterilisation – Female: • Risk of operative complications • Effect on long-term health – Regret 6%, uncomplicated female sterilisation has no long term effects on menstruation or the genital tract – Male: • Risk of operative complications • Effect on long-term health
  • 27. Transcervical sterilization • Fallopian tubes approached through cervix instead of abdominal incision. • Essure permanent birth control system: coil mechanism. • Quinacrine-induced occlusion: 2 doses of quinacrine pellets, one month apart, between day 7 and 10 of the menstrual cycle. ?carcinogenicity • Erythromycin (animal studies). • Intratubal Ligation device and two step Adiana system
  • 29.
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  • 34. Who is getting infected
  • 35. HIV and Maternal/infant mortality HIV is the single largest cause of maternal and infant death in several parts of sub-Saharan Africa and has reversed previous gains made in some countries. Pregnancy may increase HIV acquisition.
  • 36. Contraception and HIV: What to consider Women at risk Women infected for HIV with HIV Disease Drug Prevention Acquisition Infectiousness interactions progression
  • 37. HIV acquisition • Large prospective cohort study, funded by the U.S. NICHD, was conducted by FHI and collaborating institutions among some 6,100 family planning clients in Uganda, Zimbabwe, and Thailand. • Involved HIV-negative, 18- to 35-year-old women in three exposure groups of roughly equal size: combined oral contraceptive (COC) users, DMPA users, and women not using hormonal contraception. • Designed specifically to evaluate the relationship between the use of low-dose COCs or DMPA and HIV acquisition • Four-year study found no overall association between the use of either combined oral contraceptive (COC) pills or depot-medroxyprogesterone acetate (DMPA) and HIV acquisition.
  • 38. HIV acquisition • Women were tested for HIV infection every 12 weeks until they became infected or had been followed for 15 to 24 months (overall retention rate of 91 percent). • Strongest study to date exploring this issue. However, not a randomized controlled trial, therefore cannot provide evidence to establish a direct cause-effect relationship. • Morrison C, Richardson B, Mmiro F, et al. Hormonal contraception and the risk of HIV acquisition. AIDS 2007;21(1):85-95.
  • 39. HIV Acquisition: For Most, No Additional Risk With Hormonal Methods, IUDs • A study in South Africa (Palesa Study) found that the numbers of new cases of HIV were similar among women using either progestin- only injectables or COCs and among women not using any hormonal method, after adjusting for differences in sexual risk behaviors and the presence of STIs. • Limited evidence from other studies also suggest that women using the copper-bearing IUD are not at greater risk of acquiring HIV. Kleinschimdt 2005
  • 40. HIV Acquisition: High risk groups • Among populations at high risk of HIV exposure, such as sex workers, some studies (Mombasa study) find that hormonal contraception increases the risk of HIV acquisition. For example, sex workers in Kenya using COCs or DMPA had a 1.5 times and 1.8 times greater risk, respectively, of acquiring HIV than sex workers who were not using these methods, after adjusting for condom use and number of sexual partners. Lavreys 2005
  • 41. HIV infectivity: Limited and Unclear Evidence on Viral Shedding • Unknown whether HC use by HIV-infected women increases their risk of infecting sexual partners. • Limited studies: Only 2 studies have been prospective, and the results of cross-sectional studies of HIV shedding from the genital tract are conflicting, perhaps due to relatively small study samples.
  • 42. HIV infectivity: Limited and Unclear Evidence on Viral Shedding • How to determine a woman's HIV infectiousness also is unclear. – Amount of HIV genital shedding necessary to increase infectiousness is unknown. – Questions remain about the best technique for detecting HIV in genital tract secretions. • No consensus exists on what indicators best reflect the risk of HIV infectivity.
  • 43. HIV infectivity • 213 HIV-infected family planning clients in Mombasa, Kenya (2004) – Only prospective study of the direct effect of hormonal contraceptive use on genital tract shedding of HIV – Detected a significant but modest increase in cervical shedding of HIV-1 DNA after initiation of hormonal contraceptives. Not noted for separate groups. • Increase in cervical shedding of HIV-1 DNA associated with hormonal contraceptive use overall was not accompanied by an increase in cervical shedding of HIV-1 RNA. – Possible explanation that HC use attracts infected cells to the genital mucosa (evidenced by increased HIV-1 DNA) but does not increase local viral replication in the mucosa (which increased HIV-1 RNA would reflect).
  • 44. HIV infectivity • Another prospective study, conducted in 2005 among 967 U.S. women (654 of whom were HIV-infected), found that: – Progesterone-based contraceptives appeared to raise the number of cervicovaginal inflammatory cells, assumed to be associated with increased HIV-1 viral load in genital secretions. – Limitation: small number of participants using progesterone contraception - the analysis had little statistical power. • IUDs do not appear to increase the infectiousness of women with HIV. The two studies that have looked at the prevalence of HIV-infected cells in the cervix found no greater shedding due to IUD use.
  • 45. HIV progression: Could Hormonal Methods Speed Up Disease? • Does the use of HC during the early or later stages of HIV infection affect disease progression? • Only evidence so far that HC use might affect HIV disease progression comes from a prospective study conducted among 161 sex workers in Mombasa, Kenya. This evidence suggests that using HC at the time of infection — before women know that they are infected — may accelerate HIV-related deterioration of the immune system and thus speed the natural course of the infection. • Evidence of risk considered insufficient to warrant any restrictions on hormonal contraceptive use by women with HIV/AIDS or women at high risk of infection.
  • 46. Viral set point and diversity • In Kenya study, median viral set point was significantly higher among women using the DMPA at the estimated time of HIV infection than among women using no hormonal contraception at that time. Persisted during follow-up (median of 34 months). However, continuing use of DMPA did not appear to further increase viral load. • Overall, use of oral contraceptive pills was not associated with higher viral set points. But in subset of 156 HIV-infected sex workers use of either OCs or DMPA at the time of HIV infection was associated with acquiring genetically diverse virus populations from one partner. • Limited evidence suggests any impact HC use may have on HIV disease progression occurs during the early stages of the infection.
  • 47. Drug Interactions: Do ARVs Reduce Effectiveness of LD Hormonal Contraceptives? • Limited evidence suggests certain ARVs could alter blood levels of contraceptive hormones in women using low dose OCs. • Two small studies reported that the ARVs nevirapine and ritonavir could lower both estrogen and progestin levels enough to increase risk of contraceptive failure. Both studies evaluated the effect of just a single dose of COC. No information is available on women taking a pill every day. Thus, it is not clear whether or how much contraceptive effectiveness would be reduced. • Despite the theoretical concern about contraceptive effectiveness, women taking ARVs still generally can use COCs.
  • 48. Drug Interactions: Do ARVs Reduce Effectiveness of LD Hormonal Contraceptives? • The few studies available find that ARVs have little or no effect on hormone levels in DMPA users with HIV. Providers can emphasize returning on time for the next injection. This will help to ensure that hormone levels remain high enough to prevent pregnancy. . • Hormonal contraceptives do not appear to reduce the effectiveness of ARVs.
  • 49.
  • 50. Contraceptive Options for HIV-infected Women • Women with HIV have a right to decide whether they want to become pregnant and bear children. • If an HIV-infected woman chooses not to have children, or wants to space her family, she should be able to make informed, voluntary decisions about contraception and then receive her method of choice. Such use of contraception by HIV-infected women is an important way to reduce HIV-positive births. • HIV-infected women can use most contraceptive methods safely.
  • 51. Contraceptive Options for HIV-infected Women • Need to weigh the advantages and disadvantages of various methods and consider the effects of each method on her own health, risk of infecting others with HIV, and response to HIV/AIDS treatment. • Counsellors should help each HIV-infected woman assess her contraceptive needs, review all options available to her, and determine whether she and her partner will be able to use a particular method or combination of methods safely, correctly, and consistently.
  • 52. Contraception and HIV: Options Barrier methods
  • 53. Condom Effectiveness Contraceptive Contraceptive STI/HIV effectiveness effectiveness effectiveness Consistent and Typical use correct use Male 97% 86% Proven to protect Condom against STI/HIV Reduces HIV incidence by 80- 97% when used correctly and consistently Female 95% 79% Effective in vitro. Condom Limited data on efficacy in real use
  • 54. Condoms • Condoms should be promoted, together with an additional form of contraception, as an ideal method of contraception. • This reduces the transmission of HIV to her current and possible future partners if they are at risk of HIV infection. If they are already infected the use of condoms is still advised, as in addition to the prevention of conception, it prevents the transmission of sexually transmitted infections and prevents infection with new strains of HIV • The effect of condoms is not altered by the use of ART.
  • 55. Other barrier methods • Barrier methods other than condoms offer only modest protection against pregnancy and are generally not recommended for women with HIV. • Frequent use of spermicides containing nonoxynol-9 (N- 9) may increase the risk of reinfection with other strains of HIV because N-9 can disrupt the lining of the vagina, making it more vulnerable to infection. Studies have also shown that N-9 offers no protection against STIs. • Diaphragms and cervical caps are not recommended for women with HIV or AIDS and women at high risk of HIV infection because they are usually used with spermicides containing N-9. • Recent study (Mira trial) showed no increase HIV protection with diaphragm use. (Lancet July 2007)
  • 56. Contraception and HIV: Options ‘Modern’ methods of Contraception
  • 57. Hormonal methods • The World Health Organization (WHO) recommends that HIV-infected women can safely use hormonal contraceptives — including combined oral contraceptives (COCs), the injectables depot-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET- EN), and implants such as Norplant. • Questions remain about the effects of hormonal contraception on a woman's HIV infectiousness and disease progression and about the consequences of interactions between these methods and antiretroviral (ARV) drugs.
  • 58. IUDs • In 2004 the World Health Organization updated its guidance, based on recent research, and now advises that women with HIV can generally start using either a copper-bearing IUD or a hormonal IUD. Specific guidance includes: – Women with HIV who do not have AIDS can generally have copper-bearing and hormonal IUDs inserted. – Women with AIDS who are on ARVs and are clinically well generally also can have the IUD inserted. – IUD insertion usually is not recommended for women who have AIDS and are not on ARVs, however. The IUD also is not usually recommended for women who are using ARVs but are not clinically well. – If an IUD user becomes infected with HIV or if an IUD user with HIV develops AIDS, the IUD generally does not need to be removed. She should be monitored for signs of PID.
  • 59. Sterilisation • Offers couples a safe, highly effective, permanent method of contraception. May be a good option for HIV- positive women and their partners who have decided to forgo or end childbearing, and it raises no particular health concerns for HIV-infected women. • HIV-discordant couples in which the man is HIV-negative and the woman is HIV-positive may want to consider male sterilization because it does not depend on the woman's health. • Studies show a reduction in consistent condom use in couples after one partner has undergone sterilization. Couples should be counseled about the importance of using condoms if they might be at risk of HIV infection. • Avoid coercion.
  • 60. Female Sterilization and Vasectomy are Safe • For people with AIDS, special arrangements should be made to perform the procedure in a setting with a qualified provider, with appropriate equipment and support. • Women or men with acute AIDS-related illness may have to wait until their condition improves before undergoing the procedure
  • 61. Emergency contraception • Should be made available for all women who use barrier contraception only. • Classical contra-indications for hormonal contraception such as previous ectopic pregnancy, cardiovascular disease, migraine, liver disease and breastfeeding are not considered contraindications to emergency contraception use. • The use of antiretroviral therapy should not preclude the use of emergency contraception and the favoured method should be progesterone based morning after pill for women who are on ART.
  • 62. Other methods • Lactational amenorrhoea method: – Women who are infected with HIV or who have AIDS and choose to breastfeed their infant can use LAM. – Exclusive breastfeeding for the first six months of a baby’s life is the safer breastfeeding pattern to minimize the risk of HIV transmission through breastmilk. – If a woman’s monthly bleeding returns before six months, she will need another contraceptive method while continuing to breastfeed exclusively. – Women with HIV and their health care providers need to consider the infant feeding options available and to weigh their various risks and consequences.
  • 63. Summary • Increasing number of women will be aware of their HIV status • Providers need to be aware of new data to advise HIV infected women regarding their options to prevent unwanted pregnancies
  • 64. Contraception and HIV acquisition Method & Strength of evidence Comment HIV acquisition of interaction Injectable progestins - General population + Higher risk groups (SWs), younger age group, HSV2 negative COCs - General population + Higher risk groups (SWs), younger age group IUDs - General population
  • 65. Contraception and HIV transmission Method & Strength of Comment HIV transmission evidence Injectable progestins - General population ?+ Higher risk groups (SWs), COCs - General population ?+ Higher risk groups (SWs) IUDs - General population
  • 66. Contraception and HIV progression Method & Strength of Comment HIV progression evidence Injectable progestins - General population + Worse prognostic disease in higher risk groups (SWs). Worse disease progression? (from RCT with IUDs) COCs + Worse prognostic disease in higher risk groups (SWs). Worse disease progression? (from RCT with IUDs) IUDs - IUD use appears safe in HIV+ve women.