Managing HIV in pregnancy in a community-based sexual health clinic: a decade in review

Abstract

The management of HIV in pregnancy has evolved significantly over the past 10 years as our experience of combination antiretroviral therapy (ART) has grown. We reviewed 109 pregnancies which were managed at our community-based integrated HIV and sexual health clinic to investigate preconception and antenatal care, and trends in ART over time. We document an increasing proportion of pregnancies in which the mother was aware of her HIV status pre-conception and conception on ART. Pre-conception care was sought in a minority of cases, and many women did not present for first antenatal review until the end of the second trimester. Of 108 live births, there was one case of vertical transmission (0.93%). While our study demonstrates the efficacy of current strategies to prevent mother to child transmission of HIV infection, more could be done to encourage HIV-positive women to seek preconception advice and to attend for early review in the first trimester.

Keywords

pregnancy HIV women antiretroviral therapy ART prevention PMTCT integrated care

INTRODUCTION

The management of HIV in pregnancy in the UK has evolved significantly over the past 10 years. From initially standardizing the use of antiretroviral therapy (ART) and regulating the optimal mode of delivery, greater experience in the management of pregnant women living with HIV has allowed care to be tailored to the needs of the individual woman.

In 2001, Zidovudine (AZT) monotherapy in combination with a pre-labour Caesarean section (AZT + PLCS) was initially recommended in all clinical scenarios.¹ Triple therapy was suggested as a potential option for women requiring combination antiretroviral therapy (cART) for their own health; however, robust trial data were lacking and the use of cART was initially uncommon.¹

From 2005 the former regimen (AZT + PLCS) was recommended only for women with a low HIV viral load (<10,000 copies/mL) who did not require cART for their own health.² Instead, the prescription of short-term triple therapy (‘START’) or the initiation of long-term cART (if required by the mother) became the mainstay of treatment, with the aim of achieving an undetectable plasma HIV viral load and planning for a vaginal delivery.

More recently, the emphasis of care for HIV in pregnancy has extended beyond these pharmacological and physical interventions to reduce the risk of mother-to-child transmission. Following the 2008 British HIV Association (BHIVA) guidelines, the need to consider a holistic approach to each woman's pregnancy has been increasingly recognized.³

All pregnant women in the UK are offered antenatal care routinely; however, receiving specialized antenatal care in the context of HIV infection is particularly important. Pre-conception advice has the potential to maximize fertility while minimizing the risk of infection to negative partners. Once pregnant, attending for early review in the first trimester allows the physician and patient adequate time to decide on the best strategy for ART and delivery. Antenatal care also offers the opportunity to discuss disclosure, and to arrange HIV testing of sexual partners.

Our community-based genitourinary medicine/family planning/HIV service provides integrated sexual health care for men and women. We have offered pre-conception, antenatal and postnatal care for HIV-positive women under one roof since 2000. Pre-conception advice is provided formally in a designated clinic, but can be sought informally during routine review. Infants were traditionally followed up at the paediatric clinic in the acute hospital. Since 2006, our on-site family clinic run jointly by an adult physician and a paediatrician has allowed mothers and infants to be seen together, which facilitates neonatal HIV testing. In this review, we aim to describe our experience of managing HIV in pregnancy over 10 years from 2000 to 2010, illustrating pre-conception and antenatal care, and highlighting how our use of ART has changed over time.

METHODS

We reviewed our prospective database which documents all women who received care for HIV in pregnancy at our clinic from September 2000 to November 2010. Supplementary data were obtained from retrospective case-note review. Data analysis and descriptive statistics were prepared using unadjusted odds ratios (ORs) in STATA version 11.0 (Stata Corp, College Station, TX, USA). Due to a smaller number of pregnancies occurring between 2008 and 2010, analyses are presented in two time periods from 2000 to 2004 and 2005 to 2010.

RESULTS

One hundred and twenty-eight pregnancies were documented in the time period of the study. Nineteen cases were excluded from further analysis: care was transferred to another HIV centre in early pregnancy in five cases; there were five first-trimester miscarriages; five referrals for termination of pregnancy and HIV was diagnosed postpartum in three cases. One further case was lost to follow up and did not attend for antenatal care. One hundred and nine pregnancies among 97 women were included in the review: 10 women received care for HIV in pregnancy on two occasions and one woman received care three times. There were no multiple births. The baseline demographics of the study population are illustrated in Table 1.

Table 1

Baseline characteristics of 97 women at first pregnancy (n = 97)

Characteristic	Result
Median age at first pregnancy (n = 97 women)	30 years (range 16–42 years)
Ethnicity (n = 97 women)	86 (88.7%) Black African
	7 (7.2%) Caucasian
	4 (4.1%) South East Asian
First pregnancies in which women reported a regular male partner (RMP) (n = 97 women)	82 (84.5%) women reported an RMP
	7 (7.2%) women did not report an RMP
	8 (8.3%) women – no data
HIV status of regular male partners (n = 82 RMPs )	29 (35.4%) HIV positive
	31 (37.8%) HIV negative
	22 (26.8%) Unknown HIV status
Median gestation at which women notified clinic of first pregnancy (n = 97 women)	18 weeks (range 3–38 weeks)

Preconception and antenatal care

In our clinic the proportion women aware of their HIV diagnosis prior to their first pregnancy has increased from 21% (2000–2004) to 49% (2005–2010). This is described in Table 2, where ORs illustrate the change in frequency of each event between the two time periods. Of these women (n = 37), 24% attended for pre-conception counselling, and attendance was more likely in women on ART prior to conception (54%, unadjusted OR 12.8, P = 0.002). In pregnancies where the mother had received care for HIV in pregnancy previously (n = 12), 4/12 (33%) attended for pre-conception advice and 3/12 (25%) conceived on ART.

Table 2

Pre-conception care and prescription of antiretroviral therapy in pregnancy 2000–2010

Characteristic	Total Cohort	2000–2004	2005–2010	Unadjusted odds ratio(P value)
HIV diagnosed before first pregnancy (n = 97)	37/97	8/38	29/59	OR 3.63
	38%	21%	49%	P = 0.006
				95% CI 1.37–9.63
Conception on cART when HIV diagnosed before first pregnancy (n = 37)	13/37	1/8	12/29	OR 4.94
	35%	13%	41%	P = 0.135
				95% CI 0.48–50.57
Attendance for preconception counselling whenHIV diagnosed prior to first pregnancy (n = 37)	9/37	2/8	7/29	OR 0.95
	24%	25%	24%	P = 0.960
				95% CI 0.15–5.99

cART = combination antiretroviral therapy; OR = odds ratio; CI = confidence interval

First presentation for antenatal care occurred at a median of 18 weeks gestation (n = 109 pregnancies, range 3–38 weeks), with first presentation for care occurring beyond 30 weeks gestation in 13 pregnancies (13/109 = 12%) First presentation was earlier in women aware of their HIV status pre-conception (median 12 weeks, range 10–16 weeks); earlier again in those who conceived on ART (median 8.5 weeks, range 7–12 weeks); and also in those who attended for pre-conception advice (median 8 weeks, range 6–12 weeks). The median CD4 count and HIV viral load in pregnancies where the mother did not conceive on ART was 400 cells/µL (n = 90, range 30–1000 cells/µL) and 7333 copies/mL (n = 90, range 10–1,000,000 copies/mL), respectively, at the time of first antenatal review. A CD4 count less than 350 cells/µL was recorded in 42% of these pregnancies.

The majority of women reported having a regular male partner at the time of their first pregnancy (n = 82, 84.5%), and a significant number of couples were serodiscordant (n = 31, 37.8%). In serodiscordant couples where the woman was aware of her HIV status prior to her first pregnancy, 31% (5/11) attended for preconception advice. The HIV status of regular male partners was unknown in 28.6% of first pregnancies, despite the availability of HIV testing within our clinic.

A sexual health screen was performed in all 109 pregnancies, with symptomatic bacterial vaginosis and candida being recorded in 11% and 22% of pregnancies in turn. Sexually transmitted infections were uncommon: genital warts were recorded in eight pregnancies; chlamydia in three pregnancies; herpes simplex virus in three pregnancies and trichomoniasis in a single pregnancy. Neither cases of gonorrhoea nor active syphilis were found.

Antiretroviral therapy and mode of delivery

Conception on ART in first pregnancy has become more common in our clinic (13% 2000–2004 versus 41% 2005–2010, OR 4.94, P = 0.135), mirroring the trend for more frequent prepregnancy HIV diagnoses. Nineteen of 109 pregnancies were conceived on cART in total; however, none of these were didanosine- or efavirenz-containing regimens. We have previously avoided both of these antiretroviral drugs in women with child-bearing potential, due to concerns over maternal and fetal toxicity.^3,4 Recent guidance provides reassurance that the avoidance of efavirenz is unnecessary in future.⁵

Table 3 summarizes the prescription of antiretroviral therapy and mode of delivery in 99 pregnancies. Ten pregnancies between 2000 and 2004 in which dual nucleoside reverse transcriptase inhibitor (NRTI) therapy was prescribed are not included for simplicity. In accordance with national guidelines, the use of AZT monotherapy in combination with a PLCS decreased from 35% of pregnancies in 2000–2004 to 7% of pregnancies in 2005–2010 (OR 0.14, P < 0.001). Similarly, we have documented an increase in the number of vaginal deliveries (8% versus 26%, OR 4.36, P = 0.020).

Table 3

Antiretroviral therapy (ART) and mode of delivery (MoD) 2000–2010

	Total	2000–2004	2005–2010
ART and MoD	n = 99	n = 37	n = 62	Unadjustedodds ratio(P value)
Monotherapy + PLCS	17 (17%)	13 (35%)	4 (7%)	OR 0.14
				P < 0.001
				95% CI0.04–0.51
cART + PLCS	43 (43%)	15 (41%)	28 (45%)	OR 1.09
				P = 0.42
				95% CI0.62–3.20
cART + VD	19 (19%)	3 (8%)	16 (26%)	OR 4.36
				P = 0.020
				95% CI1.13–16.90
Any ART + ECS	20 (20%)	6 (16%)	14 (23%)	OR 1.38
				P = 0.562
				95% CI0.466–4.061

cART = combination antiretroviral therapy; OR = odds ratio; CI = confidence interval; PLCS = pre-labour Caesarean section; VD = vaginal delivery; ECS = emergency Caesarean section

cART was prescribed in 78 pregnancies. Less than four weeks of treatment had been taken at the time of delivery in three pregnancies; due to late presentation in one case, premature delivery at 29 weeks in another and due to a late treatment switch from AZT monotherapy in a further pregnancy. In the remaining 75 pregnancies, an undetectable viral load was achieved predelivery in 80% of cases (60/75, 80%). In those with a detectable HIV viral load at delivery (15 pregnancies), the median HIV viral load at delivery was 1034 copies/mL (range 94–9000 copies/mL). In these pregnancies women frequently presented after 20 weeks gestation for antenatal care (10/15, 66%); frequently delivered prior to 37 weeks gestation (6/15, 40%), and most often by emergency Caesarean section (8/15, 53%). Triple postexposure prophylaxis was provided to the neonate in each case.

The median gestation at the time of delivery was 38 weeks in our cohort overall (n = 109, range 27–41 weeks), which is largely driven by the 60 pregnancies in which a pre-labour Caesarean section was arranged at 38 weeks gestation. In the 19 pregnancies delivered prior to 37 weeks gestation, 14 had been prescribed cART (protease inhibitor [PI] therapy in 10 cases, non-NRTI [NNRTI] therapy in 4 cases). While lacking statistical significance, our results suggest a trend towards an increased likelihood of premature delivery with the use of cART compared with AZT monotherapy (unadjusted OR premature delivery if cART 2.09, P = 0.35).

Pregnancy outcomes and postnatal care

Of 109 pregnancies, 108 infants were live-born. One infant was vertically infected with HIV (1/108, 0.93%), in the context of poor maternal adherence to ART. One child was diagnosed with Down's syndrome; however, no other congenital anomalies were noted. Maternal postnatal review occurred within four weeks of delivery in 79 pregnancies (79/109, 72%) and postnatal contraceptive advice was documented in 71 cases (71/79, 90%). No mothers were known to have breast fed. In 65 pregnancies, short-term cART was discontinued postdelivery. A genotypic HIV resistance test was performed within four weeks of delivery in all cases, and no evidence of resistance was documented. All babies were tested for HIV on day 0 (100%). Eleven babies born in other hospitals had paediatric follow-up elsewhere. Of the 97 attending locally, 95 babies had a second blood test at 6–8 weeks of age (98%), and 92 babies had a third blood test at after 3–5 months (95%), following which BCG was arranged. Follow-up to 18 months of age was achieved in 77/92 (84%, 5 still too young). Of the 15 babies not seen at 18 months of age, four were known to have gone abroad, nine had moved to other UK centres and two were lost to all follow-up (both of these were lost after 3 negative infant blood results).

DISCUSSION

We report our experience of providing care to HIV-positive women during pregnancy over the past 10 years, during which time antenatal care has evolved, and the use of antiretroviral therapy and recommended mode of delivery has changed significantly.

In keeping with the 2011 NSHPC update and an earlier audit from east London, there has been an increase in prepregnancy HIV diagnoses and conception on ART in our cohort.^6,7 Such increases may reflect the higher CD4 count threshold at which long-term cART is now initiated in non-pregnant adults,⁸ together with an increase in HIV testing out with the antenatal setting. Conception on antiretroviral therapy was associated with the attendance for pre-conception counselling in our clinic. Anecdotal evidence suggests that women in our clinic on cART are more engaged with health-care services and more aware of the benefits of preconception advice. Yet in a significant number of pregnancies the HIV status of the male partner was unknown; and in serodiscordant couples with the potential to request preconception advice, such counselling was not documented in the majority of cases. We have not captured in how many of these cases the pregnancy was planned, nor in how many of these serodiscordant couples the negative male partner was aware of the woman's HIV status at the time of conception. Similarly, we cannot account for women who may have learned about techniques for safe conception from alternative sources. However, our data highlight a number of pregnancies in which the male partner may have been exposed to unnecessary risk of HIV infection. This emphasizes the need to inform all HIV-positive women about the importance of specialist preconception advice. Routinely discussing techniques for safe conception with pre-menopausal women, regardless of intended plans to conceive, may benefit both women and their partners.

Our data illustrate the prescription of ART in accordance with the 2005 and 2008 BHIVA guidelines:^2,3 we have documented decreased use of zidovudine monotherapy in combination with a PLCS, and a concomitant increase in the number of pregnancies in which cART was prescribed and vaginal deliveries occurred. Previous studies have associated the use of triple therapy with delivery prior to 37 weeks gestation,^9,10 and our results suggest that there is a similar trend in our cohort.

The number of pregnancies in which an undetectable viral load was recorded predelivery is similar to that reported in a recent Italian study,¹¹ and we would like to highlight the importance of regular measurements of HIV viral load in the third trimester, good communication between patients and the multidisciplinary team, and the need for active follow-up of patients who may fail to attend for venepuncture. Seven of 15 pregnancies in which there was a detectable viral load at delivery occurred in women who were aware of their HIV status prior to conception, yet the majority presented for antenatal review after 20 weeks gestation. There may be a role for actively encouraging all HIV-positive women to present for HIV antenatal care as soon as they become aware of their pregnancy. There is also a broader need to encourage all pregnant women, and women considering pregnancy to be aware of their HIV status in time to benefit from optimal pre-conception and antenatal care including adequate ART. Women diagnosed in the antenatal setting should receive a specialist HIV review without delay, which relies on both services developing seamless patient pathways.

The number of vertically infected babies among women who have attended our service is low (0.93%), which compares favourably with national figures.⁶ Encouragingly, we have documented a high rate of infant follow-up. Our data do not capture whether the re-location of our paediatric follow-up clinic has in itself contributed to the completeness of our paediatric data. However, preliminary qualitative works suggests that women find our on-site family clinic convenient in combining maternal and neonatal review into a single clinic visit, and patients have commented that this multidisciplinary approach increases patient confidence in the continuity of care between paediatric and adult services.

Our data are limited by the relatively small total number of pregnancies which we have recorded, in comparison with other larger urban centres with bigger clinic populations. Consequently, results are limited to unadjusted associations, which do not allow for the analysis of confounding factors and effect modifiers. Given the location and organization of HIV service provision locally, our findings may not be representative of other clinic cohorts.

CONCLUSION

Over the past 10 years, the management of HIV in pregnancy has grown significantly. More women are conceiving on cART and more women are having vaginal deliveries. Women may benefit from greater emphasis on pre-conception advice and antenatal care, particularly among treatment-naive women and serodiscordant couples. We have shown that high rates of infant follow-up can be achieved in a community-based setting. Further study should investigate the factors associated with a lack of virological suppression at the time of delivery and late presentation for care. Increasing women's awareness of the variety of interventions available to reduce the risk of HIV transmission to their partners and their babies may increase the reproductive choices of this special population, and improve the quality of life of women living with HIV in the UK.

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