ART services for HIV-positive people

November 18, 2010Carole No Comments »

A positive blood test for HIV used to be a death sentence. With the development  of highly active antiviral therapy (HAART), patients are able to decrease their viral load to non-detectable levels. HAART therapy is the use of at least three different antiviral medications from two different class types  in daily doses to depress viral replication. In one study of almost 400 couples, when  HAART therapy was used,  transmission of the HIV between heterosexual couples was reduced by 80%.  The World Health Organization (WHO) has numerous publications regarding worldwide experience with HIV prevalence, diagnosis and treatment. (Note that you will find the acronym ART used in the WHO literature, but there it stands for anti-retroviral treatment, not assisted reproductive technology. I will use ART to refer to assisted reproduction in this post). In any case, the introduction of a combination of anti-viral drugs early in the progression of the disease has largely caused HIV to be reclassified as a chronic disease to be managed and allowing patients to have expectations of leading a relatively normal life.

HIV-infected patients desire to have families like everyone else but are placed at risk for transmitting HIV to their non-infected spouse and partner through sexual intercourse.  ART procedures such as sperm washing and sperm injection can provide a safer alternative to unprotected intercourse for these couples who want to conceive. Dr. James D.M. Nicopoullos, MD of the Assisted Conception Unit of Chelsea and Westminster Hospital in London recently published “A decade of the United Kingdom sperm washing program: untangling the transatlantic divide” in Fertility & Sterility (Vol. 94, No. 6, November 2010). In his paper, Dr. Nicopoullos looks at the very different models for delivery of ART services to HIV patients in the US and Europe.

In Europe, the Center for Reproductive Assisted Techniques for HIV in Europe (CREATEhE) was created to gather and disseminate knowledge, experience and results from centers offering ART services to HIV discordant couples all over Europe. CREATEhE has data collected from over 3000 treatment cycles from nine centers and did not find one case of HIV seroconversion to an uninfected partner or resulting child when ART was used. The Human Fertilisation and Embryology Authority which regulates and licenses ART in Europe maintains that it is ethical to provide these services if adequate precautions are taken to prevent disease transmission.  Much more controversy exists in the US about the ethics of providing fertility services to HIV positive patients. As HAART treatment for HIV becomes routine and patients continue to live normal lives perhaps ethical concerns about providing treatment will slowly subside.

If you are an HIV patient in the US, you are less likely to find ART clinics that offer these services, although there are some clinics and and a few research programs that work together to provide services. Why are ART services to HIV patients difficult to find in the US? An early discouragement to providing services was provided by the  CDC in 1990 when it recommended NOT to use washed sperm from HIV positive persons for intrauterine insemination(IUI). In spite of thousands of safe IUI cycles using washed sperm reported by clinics all over the world since 1990, the CDC has not changed its recommendation. Because the CDC has no regulatory powers, the CDC recommendation did not make IUI with washed sperm from HIV positive men illegal. However, some states have criminalized ART services for HIV positive patients. Knowingly using sperm from an HIV positive person for insemination is an illegal act ranging in severity from misdemeanor to felony in states including Florida, California, Illinois, Delaware and Indiana.

The American Society for Reproductive Medicine (ASRM) has issued the ethics statement,”Human Immunodeficiency Virus and Infertility Treatment”, which can be downloaded from the ASRM webpage.  The main points are:

  • Human immunodeficiency virus (HIV) is a serious, chronic disease most prevalent among younger patients who are likely to want children.
  • HAART  can effectively minimize the risk to patients, partners and offspring.  Using HAART, c-section delivery and no  breast-feeding reduces the risk of newborn infection to ~2%.
  • Sperm preparation techniques used with either insemination, IVF or ICSI have been shown to be very effective at preventing infection of uninfected partners or resulting children.
  • ASRM recommends that fertility clinics, if they are equipped to provide the services, should offer these services to HIV patients who are willing to risk infection, even if reduced, through these techniques.

ASRM has also published specific guidance for providing services in “Guidelines for reducing the risk of viral transmission during fertility treatment” which can be downloaded here. This guidance discusses existing regulations about infectious disease transmission as well as specific technical lab procedures that can be used to minimize risk.

Other Federal Regulation. The Food and Drug Administration is very concerned with the transmission of infectious disease and have been given full legal authority to oversee the use of third parties who wish to donate sperm or eggs for use in ART procedures. I’ve posted previously about the FDA’s role in requiring very specific screening and testing of prospective donors. Only sexually intimate partners are exempt from this screening and testing. Therefore sexually intimate couples where one or both partners are HIV positive are also exempt from this ruling. But the FDA also clearly prohibits the use of gametes from any HIV positive donor to a person or couple, whether or not the recipient couple is HIV positive.

Clinical practice. Because clinics providing ART services to HIV patients want to minimize the risk of disease transmission, couples can expect to be tested for HIV before beginning treatment to verify that HAART therapy is working and HIV viral loads are undetectable. Most, if not all clinics, would likely delay starting any ART therapy until the viral load is non-detectable in the blood. ASRM recommends that detectable virus in the blood be less than 10,000 viral copies per milliliter before ART treatment and that processed sperm samples be further tested for HIV RNA before use. Most CREAThE clinics also require post-processing testing of the sample for viral particles.

Technically speaking, what can be done to “clean” up a sperm specimen so it can be used for ART?

Sperm washing. Start with a specimen from a partner or spouse who is HIV positive but on HAART therapy with non-detectable virus in his blood. The ejaculate can be washed using centrifugation through a thick liquid or gradient which removes most of the seminal plasma fluids that accompany the sperm in the ejaculate. You can see a graphic depiction of sperm washing here, along with one couple’s story. To further decrease the risk of transmission, sperm in the pellet and the fluid from the sperm can be subjected to additional testing using PCR to detect individual virus particles.  Only processed samples that test negative would be used for insemination.

Additional processing can be used on samples for IVF or ICSI. Because much less sperm is required for IVF/ICSI compared to insemination, lab procedures such as swim-up that eliminate most of the sperm can be used to provide additional selection against the virus. Further clean-up can be done using a technique called a swim-up which works like its name. A sperm pellet is overlain with warm culture medium and the tube is placed in the incubator for a period of time (perhaps an hour) during which the most aggressive swimming sperm swim-up out of the pellet and up to the upper part of the fluid column where they can be selectively removed, leaving more sluggish packed sperm and associated virus behind.

ICSI. Dr. Mark V. Sauer, a US physician, published his experience performing hundreds of HIV ART cycles over a decade.  Using processed sperm for ICSI (without any post-processing testing), he did not have one case of HIV infection, suggesting that processing for ICSI and exposing the egg to a single sperm may be sufficient to prevent infection. His program requires pre-ART testing  to confirm that their HAART therapy is working. Men must have test results showing <50,000 viral copies/mL and high CD4 counts (>250 cells/mm3, indicating good immune system function) over a 6-month period before initiating treatment. Extensive sperm processing was also performed using a combination of centrifugation through a gradient and swim-up techniques.

Research Program. Dr. Anne Kiessling started the SPAR program to give ART clinics a partnering lab that would process and test sperm for viral load for clinics who felt their own facilities were not adequately equipped to take on this task. SPAR stands for Special Program of Assisted Reproduction, a Bedford Research Clinical Laboratory Program, a not for profit research program. SPAR provides four services to partnering ART clinics and their ART patients:

  1. Evaluation of male and female partners for duration of disease, current health status, other co- infections, and status of antiviral therapy. Dr. Kiessling provides direct patient counseling to explain the program before treatment starts.
  2. Testing of patient’s blood and semen with polymerase chain reaction (PCR), a highly sensitive test that can detect free-floating virus particles (HIV RNA) in seminal plasma and also virus that has infected cells (HIV proviral DNA). Samples can be collected in the patient’s home and shipped to SPAR.
  3. SPAR tests the semen sample and if negative for virus, washes and cryopreserves semen. The viral negative, processed,  frozen sample is then shipped to the participating ART clinic for use.
  4. SPAR helps patients identify ART  centers that will work with SPAR processed/tested sperm. The SPAR program, in keeping with CDC recommendations, state that “Intra-uterine Insemination (IUI) is NOT an approved SPAR procedure.

A step-by-step SPAR checklist can be read here.

Using virus free sperm is not cheap. Patients are charged around $2600 to use SPAR services including counseling, testing, processing, freezing sperm and shipping to the patient’s ART clinic. The typical cost for IVF at most US ART clinics is about $12,000 dollars. (I do not have any financial interest in any of the programs described.)

Infertility services to HIV infected persons are not available everywhere in the US and where services exist, are often prohibitively expensive for many patients. However, ART can be used to maximize the chances of conceiving a healthy child  without transmitting HIV for these couples.

© 2010, Carole. All rights reserved.

Join the discussion