Maternal health, transmission and fertility

Polly Clayden, HIV i-Base

Good maternal health outcome following 218 deliveries

An oral presentation by Hermione Lyall from St Mary’s Hospital in London evaluated long-term outcome for a group of 245 HIV-positive pregnant women from a multicentre cohort in London. [1]

As is the case throughout the industrialised world, thanks to greatly improved health and survival expectations, there has been a dramatic increase in the number of HIV positive women becoming pregnant in the UK in recent years.

Few studies have evaluated the longer-term health and survival of these women.

For this study the investigators performed a chart review of all women with an HIV positive diagnosis and prospectively recorded follow up in antenatal care in five London centres between January 1998 and December 2000.

The majority of the women studied were African (n=205) and the mean age at delivery was 30.4 years.

At the first antenatal visit 183 women were defined as CDC status A, 27 B and 19 C. Overall the mean CD4 count was 353 cells and median viral load 4,700 copies/mL. At delivery the mean CD4 was 413 cells and viral load 2,168 copies/mL. 158 mothers conceived on triple therapy; 115 commenced triple therapy during pregnancy – 51 used ‘START’ (short term antiretroviral therapy), 64 continued after delivery and 10 had an unknown treatment outcome – and 69 women received only zidovudine (ZDV, AZT, Retrovir) monotherapy prophylaxis.

Elective caesarean sections accounted for the vast majority of deliveries for women receiving both monotherapy and triple therapy – 81% and 70% respectively. In addition 6% of women receiving monotherapy and 12% receiving triple therapy had vaginal deliveries and10% of women receiving monotherapy and 18% of women receiving triple therapy had emergency C-sections.

At last follow up (median 18.1 months) median CD4 and viral load were 527 cells/mm3 and 795 copies/mL, and 410 cells/mm3 and 49 copies/mL, for women receiving mono and triple therapy respectively. Two mothers progressed to category C receiving triple therapy and one receiving monotherapy, and there was one maternal death in the triple therapy group, from lactic acidosis.

The investigators reported good maternal health overall and no evidence of adverse effect of ZDV monotherapy on maternal survival to 18 months. The investigators expect to generate future data from this cohort on transmission rates, time to start ongoing therapy, combinations of HAART used and longer-term outcomes. It would also be useful to evaluate the possible effect of any ZDV resistance generated by those women receiving ZDV monotherapy and the effect on future treatment options.

Seminal super-shedding…

Steve Taylor from Birmingham Heartlands Hospital presented some research on what he termed, with a snappy display of alliteration, “seminal super shedding”’ of HIV…

In this study the investigators hypothesised that although the majority of men have lower levels of HIV in semen than in blood plasma, a minority appear to have HIV RNA in semen in excess of that in their blood plasma and that these ‘seminal super shedders’ may represent a group at greater risk of transmitting HIV-1. [2]

A group of 72 men, not currently receiving therapy, were enrolled. Overall they had a median CD4 count of 214 cells and 25 were defined as CDC status A, 17 CDC status B and 31 CDC status C, 44 were drug naïve and 28 had previous treatment experience.

Matched blood plasma and semen samples were obtained at the same time as carrying out tests for urethritis, determining viral load. The investigators defined seminal super shedding as SPVL/BPVL ratio >1.

They reported that none of the men had BPVL<400 copies/mL but 22/72 (30%) had SPVL <400 copies/mL despite detectable BPVL – this group were defined as non-shedders. 41/72 (58%) had detectable virus in semen – defined as normal shedders and 9/72 (12%) shed virus into semen in excess of blood – super shedders.

Of the nine that met the super shedder criteria, the investigators found that they had significantly higher SPVL compared to non super shedders (5.6 log 10 copies/mL vs 3.4 log/mL10, p<0.001), but their BPVL was not significantly different. They also reported that seminal super shedders tended to be older – 48 vs 35 years (p<0.02) — and the presence of urethritis was significantly over represented in the super shedders compared to the other groups 3/9 (33%) vs 3/63 (4.8%) (p=0.02). There were no significant differences in BPVL >100,000, CD4 counts and CDC status between seminal super shedders and normal shedders.

The investigators speculated that this viral replication occurs locally in the genital tract and that these individuals may have a high probability of sexual transmission of HIV.

Sperm washing and fertility treatment in the UK

Two presentations from the Assisted Conception Unit at Chelsea and Westminster Hospital in London, described both the safety and efficacy of sperm washing and the increasing demand for this and other fertility services.

Carole Gilling-Smith reported that the unit’s sperm washing programme (a safe reproduction technique for serodiscordant couples where the woman is HIV negative and the man HIV positive) had so far treated 53 couples since 1999. [3]

Both partners receive a sexual health and fertility screen; semen is then spun in a centrifuge and checked for HIV RNA. Following the success of these procedures, either intrauterine insemination (IUI) or in vitro fertilisation (IVF/ICSI) is performed – the latter if a fertility factor is diagnosed.

Thirty-eight couples received 94 cycles of IUI and 30 couples 42 cycles of IVF/ICSI. Pregnancy/live birth rates per cycle were 10.6% (10/94) for IUI and 23.8% (10/42) for IVF/ICSI. To date 15 children have been born and both mothers and children have had rigorous follow up with no reported seroconversions.

This service is largely accessed through self funding (91%), only five couples received NHS funding and more than 40% of couples referred were unable to proceed due to financial reasons. The cost per cycle is £625 and therefore prohibitive for many couples.

The investigators concluded that sperm washing at a specialist centre is a safe and effective risk reduction intervention. But they also noted: “Lack of NHS funding for this service may force couples to consider unprotected intercourse.”

Additionally Leila Frodsham, from the same group, described an audit conducted of 294 UK GUM clinics concerning requests for this and other assisted reproduction techniques among HIV discordant/concordant couples. [4]

She noted that demand is increasing due both to an increase in HIV prevalence among the heterosexual population and the effects of HAART on both life expectancy and mother to child transmission risk.

The investigators had a 63% response rate to their questionnaire (186/294), in which 83/186 clinics had received requests for information concerning conception from patients (15,211 HIV positive patients are registered at 81/83 of these clinics). Over half 49/83 (59%) of these units had referred men for sperm washing and 42/83 (51%) had referred women for assisted reproduction. However, only 12/83 (14%) units had successfully secured HIV-prevention funds from local authorities for sperm washing. In addition 96% of the 83 clinics believed that a national database of units providing these procedures would be of benefit when referring patients.

They conclude that their survey highlights the high demand for fertility services for HIV positive couples, the need to improve current services to meet this demand and the need to make information available to referring physicians. The matter of cost being a deterrent is a serious one and health authorities must address this issue.

References:

All references are to abstracts presented at 9th BHIVA Conference, 24-26 April 2003, Manchester.

Taylor GP, Sarner L, Khan W et al. AIDS-free survival of 218 HIV-infected women following pregnancy. Abstract O1.
Taylor S, Sadiq T, White D et al. Seminal super-shedding of HIV: implications for sexual transmission. Abstract O2.
Gilling-Smith C, Tamberlin B, Cox A et al. Sperm washing in the UK: evidence of safety and efficacy. Abstract O3.
Frodsham LCG, Boag F, Barton S et al. An estimation of the UK demand for fertility services in HIV-positive couples. Abstract O4.

Comment

Results from the Italian clinic where sperm washing was developed under Enrico Semprini clearly shows that this technique provides an important and safe way for a serodiscordant couple to have children where the male partner is HIV-positive and the female partner is HIV negative.

Although risks of transmission are reduced when a positive partner has an undetectable viral load in semen, viral load results from blood tests clearly do not reliably correlate and even single exposure risk can lead to HIV-infection.

The importance of providing sperm washing services as an option for such couples on the NHS should be prioritized as a health care and prevention issue.