1 To whom correspondence should be addressed at: Reproductive Medical Unit, Obstetric Hospital, 2nd Floor, University College Hospital, Huntley Street, London WC1 6AU. Email: mfi{at}easynet.co.uk
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Abstract |
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Introduction |
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Scientific background |
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Life expectancy
Prior to the use of Highly Active Anti-Retroviral Therapy (HAART), the average time from HIV infection to development of symptoms was 8 years and to death, 13 years. Prognosis has been shown to be related to age (worse if >50 years), CD4+ ve T-cell count, viral load and prior AIDS diagnosis. For example, a man with a viral load >5000 copies/ml and CD4 >200 cells/mm3 has a 3.7% chance of disease progression in 3 years whereas a man with viral load >55 000 copies/ml and a CD4 of <50 cells/mm3 has an 85% chance of progression to AIDS in 3 years.
For patients with access to treatment, the prognosis is now radically better but estimates of life expectancy, as in most diseases, are not yet robust, as HAART has been widely prescribed only since 1996. The improvement in prognosis is however related to the patient's ability to adhere to complicated treatment regimens over long periods of time, and this should be considered when estimating an individual's likely survival.
Many cohorts have examined the difference in survival between men and women but the results remain conflicting, suggesting that any effect is probably not large. Women appear to have a lower viral load for any given CD4 count or time since sero-conversion, but as treatment guidelines are now based on CD4 counts, this is of no great significance in the management of patients.
Vertical transmission
An untreated mother who delivers vaginally and breastfeeds her baby has a 28% chance of infecting her baby. Transmission is associated with viral load (there is however no viral load below which transmission never occurs), CD4 count, maternal health and prematurity (increased risk with delivery before 34 weeks). With anti-retroviral therapy, Caesarean section and bottle feeding, the risk of vertical transmission is <3%. Caesarean section has been shown to decrease transmission in a cohort study and a randomized controlled trial, but these were conducted before most women were offered combination anti-retroviral therapy. With HAART it is now uncertain whether, or how much, elective Caesarean section further diminishes the transmission rate.
At present, there is no proof that ICSI might give a risk reduction as compared to insemination with washed sperm in cases of male HIV+. Both the advantages and the disadvantages are based on theoretical ideas (less exposure to infected material versus rupture of the oocyte membrane and full entry of sperm membrane).
The effects and long term risk for the child of antiviral therapy are still under clinical investigation, but no consistent pattern of adverse outcome has yet emerged.
Effect of pregnancy on maternal health
There is little increased risk of disease progression or death caused by pregnancy itself if the mother is well at the outset.
Safety of anti-retroviral drugs during pregnancy
All anti-retroviral drugs are associated with side effects and many of these are severe. Whether the risk of serious side effects is increased, or decreased, during pregnancy is not known with certainty, but case reports of maternal deaths have led to guidance regarding didanosine and stavudine in combination.
An International Registry of Outcomes of Pregnancies exposed to anti-retrovirals has not yet identified any specific neonatal syndrome associated with exposure to any individual drug, but the numbers reported are still small. In particular, there are few data concerning exposure to anti-retroviral drugs in the first trimester. Some anti-retroviral drugs (based on animal studies) are regarded as less safe for the fetus, e.g. efavirenz.
Horizontal transmission
Estimates of the risk of transmission of HIV between heterosexual partners have shown that this is related to the presence of other sexually transmitted infections (especially ulcerative conditions), viral load and the disease stage of the infected partner. Transmission from man to woman appears more likely than from woman to man. Estimates of the risk per sexual act are imprecise. As treatment with anti-retroviral drugs lowers viral load, it is assumed that this also decreases infectivity with unprotected intercourse. However, as viral load in blood and genital secretions are not always related, this cannot be relied upon.
Risk to other patients and the therapeutic team
Ideally all labs should take universal precautions. Furthermore, as there is evidence of contamination both to samples of other patients, to other patients and to the personnel involved, it is considered good practice to have a separate laboratory and well informed and trained personnel to treat these cases.
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Ethical considerations |
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Information and autonomy
Information is generally considered as the key to enhancing patients' autonomy. There is a need for good information for the public in general, as the matter is in constant evolution: risk of transmission, progress of the disease and treatment are rapidly changing. These factors are relevant to the ethical evaluation regarding treatment of these HIV+ patients. Furthermore, informing the public will also indirectly contribute to the reduction of the spread of the disease.
Responsibility
There are several dimensions of responsibility to consider. The patients have a duty to inform the team of their HIV status, so that necessary precautions can be taken by all concerned. Patients should also comply with the most effective treatment for their condition, both for their partner's and for the future child's sake. The physician has a responsibility towards the couple and their future offspring. The specific risks involved in this treatment should be fully explained to, and accepted by, the patients. Nevertheless, the welfare of the child is a joint responsibility of the physicians and intentional parents.
In the case of HIV infection we have to distinguish two groups with their different needs: fertile and infertile couples.
The welfare of the child is not only physical, but also includes a psycho-social dimension, i.e. the risk of being orphaned at a vulnerable age and of growing up in a family which is confronted with a serious illness. There is an agreement that, in general, the death of a parent is one of the most devastating traumas a child can experience. Nevertheless, the life expectancy of HIV+ parent may be comparable to that of a parent who suffers from cancer, or from a genetic disease such as cystic fibrosis. However, it is suggested that medical assistance in ART should only be considered for the time being for sero-discordant couples so that at least one parent is likely to be able to raise the child until adulthood. This proposal may be adjusted when long term studies show that the life expectancy of the symptomatic patients with the new therapies is considerably improved.
Specific problems
Engaging in fertility treatment implies agreement to disclose the HIV status to the reproductive partner. The confidentiality regarding private medical information cannot be respected within this context.
Taking into account the risks to the future child, to the partner, the other fertility patients and to the caring team, it is recommended that all infertility patients are screened for HIV. Efforts should be made to convince patients of the benefits of knowing their HIV status. Those patients who refuse screening after full information should be treated with the same precautions as if HIV+.
In the case of specific life style risks, the physician has the right to refuse collaboration in cases which may compromise parental competence and/or jeopardize the welfare of the child, such as non-compliance to HIV treatment, drug abuse, etc. Such conditions should be evaluated on a case by case basis.
It is recommended that HIV infected people are treated in reference centres with established protocols, especially as there are often other co-viruses which necessitate specific care for the patient (e.g. hepatitis B and C). Very careful evaluation of both the clinical part of the programme (i.e. oocyte retrieval) and of the laboratory conditions should be performed to ensure safety. A separate adapted laboratory as well as separate tanks for storage of infected material is recommended.
All new protocols should be rigorously evaluated. The centre should offer care from a multi disciplinary team including clinicians (fertility experts, HIV experts, obstetricians) biologists and embryologists. These centres should also have access to counsellors/psychologists with expertise in the care of HIV patients.
Rigorously tested large studies with follow-up of couples and their children are necessary to assess the long term safety of the methods of treatment.
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Acknowledgements |
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Notes |
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