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Reproductive Choices for Men & Women with HIV

HIV (Human immunodeficiency virus) is a lentivirus (a member of the retrovirus family) that causes AIDS (Acquired immune deficiency syndrome) a condition in humans in which the immune system begins to fail, leading to lifethreatening opportunistic infections

From its discovery in 1981 to 2006, AIDS killed more than 25 million people HIV infects about 0.6% of the world's population In 2005 alone, AIDS claimed an estimated 2.4– 3.3 million lives, of which more than 570,000 were children HIV infects primarily vital cells in the human immune system such as helper T cells (to be specific, CD4+ T cells), macrophages

• WHO update ,december 2006: • the total number of people living with HIV-1 infection had reached 39.5 million • In the past, drug users were considered the most important reservoir for the virus ,with the majority of them being men • Today women are considered at higher risk for infection by heterosexual intercourse

Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk The four major routes of transmission are unsafe sex, contaminated needles, breast milk, and transmission from an infected mother to her baby at birth (vertical transmission)

Most untreated people infected with HIV-1 eventually develop AIDS HIV progresses to AIDS at a variable rate affected by viral, host, and environmental factors Treatment with anti-retrovirals increases the life expectancy of people infected with HIV The average survival time with antiretroviral therapy was estimated to be more than 5 years

The majority of HIV infections are acquired through unprotected sexual relations The transmission of the virus from the mother to the child can occur in utero (during pregnancy), intrapartum (at childbirth), or via breast feeding

HIV infection leads to low levels of CD4+ T cells through three main mechanisms: 1. direct viral killing of infected cells 2. increased rates of apoptosis in infected cells 3. killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells

Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV When several such drugs, typically three or four, are taken in combination, the approach is known as highly active antiretroviral therapy, or HAART

In the era of highly active anti-retroviral therapy (HAART), life expectancy for HIV-infected patients has dramatically improved the risk of vertical transmission has decreased to less than 1%. Three-quarters of these individuals are in their reproductive years

ART (assisted reproductive technologies) The request for reproductive assistance has been mainly for two medical reasons: 1. to overcome an infertility problem 2. To decrease the risk of horizontal transmission

Three different scenarios: both partners being infected female-only infection male-only infection HIV-discordant couples

sperm alone, independent of any sexual contact, can transmit the virus Sperm donors must be screened Sperm must be frozen & placed in quarantine for a period of 6 months

HIV in semen: HIV-1 particles and HIV-1 DNA in ejaculated sperm an alternative receptor to CD4 on sperm membrane

washing techniques

1990, Italian gynaecologist, Semprini Before the introduction of HAART Process semen from HIV-1-infected men by combining density-gradient centrifugation with swim-up of spermatozoa testing for HIV using immunofluorescence Processed semen is inserted directly into the uterine cavity with a syringe (IUI)

Criticism from his colleagues: 1. The short life expectancy of the future father 2. The very low sensitivity & therefore a high chance of a false-negative result of the test of processed semen 3. The report of one case of HIV transmission after IUI with processed semen

Arguments: 1. Harm minimization 2. Unlawful 3. Medical interventions should not be discriminatory 4. Respect to patient’s autonomy ART programs

The basic principle underlying ART is the processing of semen HIV-free, motile spermatozoa & with a normal morphology the remaining spermatozoa can be used for assisted reproductive technologies

available ART options for discordant couples for HIV male positivity: Intrauterine insemination (IUI) in vitro fertilization (IVF) intracytoplasmic sperm injection (ICSI) The risk of HIV-1 transmission by ART can never be completely eliminated

Assisted reproduction in HIV-1 patients: 1. All the semen samples may be treated with ‘‘sperm washing’’. 2. Process using a 40–80% density gradient Separate motile spermatozoa from non-sperm cells, immotile spermatozoa and seminal plasma 3. centrifuged at 400 g for 30 min 4. Remove of supernatant

5. Recovered sperm pellet resuspended in 3 ml of fresh medium 6. Performance of a centrifugation at 400 g for 10 min 7. Remove of supernatant 8. One millilitre of medium layer on the pellet 9. Incubation at 37 C for 1 h 10. Swim-up 11. PCR

The exact mechanisms involved in male-tofemale transmission of HIV-1 are as yet undefined, but circumstantial evidence indicates that genital tract infections may act as facilitating factors

In sub-Saharan and Latin-American countries, where heterosexual transfer of the virus is the leading cause of infection, there is also a high prevalence of carriers of genital infections

When IVF or ICSI? When the female partner is suffering from infertility factors the male partner had less than 1*10â ś total motile cells in the final fraction after sperm washing both partners had a combination of sub-fertility conditions

- IUI is less costly than IVF or ICSI - Poor semen qualities or a sperm yield lower than two million spermatozoa after semen processing, ICSI is the only realistic treatment option - In ICSI a single spermatozoon is injected directly into an oocyte, during which the pellucid zone of the oocyte is penetrated artificially - pregnancy rates are generally higher with ICSI than with IUI, and thus less cycles of ICSI are needed to achieve pregnancy, with less exposure to possibly HIV-1-contaminated spermatozoa

Effectively reduce HIV mother to child transmission (MTCT): zidovudine monotherapy Single-dose nevirapine highly active antiretroviral therapy (HAART) pre-labour planned caesarean section (PLCS) not breast feeding

Natural Conception in Discordant Couples with an HIV-Infected Man! the estimated risk of HIV transmission is lower than 1/1000 unprotected intercourses at blood plasma HIV RNA concentrations lower than 1700 copies/ml, and is estimated to be even lower during successful HAART, when the blood plasma HIV-RNA concentration, decreases to below the limit of detection the most important predictor of sexual HIV transmission is HIV RNA

1. Couples diagnosed as infertile being offered ART 2. the initiation of HAART 3. The exclusion or treatment of genital tract infections 4. avoidance of unprotected intercourse other than around the established time of ovulation Prophylaxis with tenofovir 245 mg provided to the woman, 36 and 12 hours before intercourse

Thanks for your Attention

HIV & Reproduction