Abstract
Co-infection with HIV-1 and -2 is rare, even in west Africa. We present the case of a 38-year-old pregnant Jehovah's Witness presenting late in pregnancy with triple infection with HIV-1, HIV-2 and hepatitis B virus. There was a successful outcome in averting vertical transmission despite objections to management based on religious and cultural beliefs.
A 38-year-old African woman presented late for antenatal booking visit at 37 weeks of gestation in October 2008. She was a practicing Jehovah's Witness and was para 2 + 0 with a girl aged 4 years and a boy aged 13 years. Antenatal screening bloods revealed dual HIV-1 and -2 seroreactivity and with evidence of chronic hepatitis B virus (HBV) infection. Her partner declined HIV/HBV testing but they reported that both they and their children had tested negative for HIV-1 and -2, two years earlier in Africa; they were unsure about previous HBV testing. The patient additionally had a history of herpes simplex virus (HSV-2) infection. The patient was reluctant to commence antiretroviral therapy (ART) as she believed that the HIV-1 and -2 results were inaccurate. She asked for normal vaginal delivery and to breastfeed upon delivery. She refused anti-HBV immunoglobulin (HBIG) for her child at delivery due to strongly held religious beliefs regarding the use of blood products.
Viral load (VL) for HIV-1 was 5300 copies/mL and HIV-2 VL was 1300 copies/mL; CD4 count was 210. HBV quantification was 2040 copies/mL. The medical advice was that the patient be initiated on an antiretroviral regimen consistent with British HIV Association (BHIVA) guidelines advocating combination therapy to reduce the risk of mother-to-child transmission (MTCT) of HIV-2 infection and with ART with activity against HBV 1 Additionally, the use of HBIG in combination with rapid HBV vaccination at birth was felt to be the best means to avoid vertical infection. Finally, prelabour elective Caesarean section (PLCS) was recommended to further reduce the risk of MTCT.
A multidisciplinary team meeting concluded that should clinical advice on management of the child postdelivery be ignored, that the child would become a ward of court.
Following the meeting, the mother accepted the medical advice and began ART with zidovudine (AZT), ritonavir-boosted lopinavir (LPV/r) and tenofovir (TDF) in line with BHIVA guidelines. 1 She was given HSV-suppressive therapy with high-dose aciclovir. VLs for HIV-1 and -2 both fell and PLCS was undertaken at 38 weeks and five days of gestation; rapid hepatitis B immunization was administered to the child at delivery. It was unnecessary to administer HBIG as mother was HbeAg negative/anti-HBe positive indicating low infectivity and she agreed to avoid breastfeeding. Follow-up at nine months, the baby has remained HIV-1 and -2 negative and HBV negative. The mother has continued ART but changed to TDF/FTC/LPV/r with undetectable VL for HIV-1 and -2 and CD4 count has risen to 310.
Discussion
Dual infection with HIV-1 and HIV-2 is rare, even in west Africa. 2 Trends in the region have shown a decline in HIV-2 infection since the mid-1990s, and HIV-1 now accounts for over 90% of infections there.2,3 Recently, studies have found that dual-infection prevalence of 0.5% within the total population of Ghana or in other terms and 2–3% of HIV infections are dual. 3
Serological cross-reactivity of HIV-1 antibodies and HIV-2 gp36 is known to occur and may wrongly classify patients as dual seropositive. 3 In our patient, confirmation of dual HIV-1 and -2 infection was achieved following a positive result with a proviral DNA assay which gave unequivocal evidence of HIV-2 infection; this facility, however, is not always available in resource-limited settings. 3
Previous studies have not clearly shown that the presence of multiple blood-borne viral infections will result in increased MTCT compared with mono-infected mothers. 4 Nevertheless, the choice of ART was crucial in achieving optimal suppression of all three viruses and hence optimal reduction in transmission of all three viral infections. AZT and 3TC have the greatest published data regarding reducing MTCT of both HIV-1 and -2 and were therefore used in our patient; TDF was added for anti-HBV activity. 1 Single-dose nevirapine, which also has growing evidence for the prevention of MTCT in HIV-1 infection, was inappropriate in view of the elevated risk of hepatotoxicity with HBV infection; in any case, HIV-2 has natural resistance against non-nucleoside reverse transcriptase inhibitors (NNRTIs). 1 The combination chosen successfully reduced all three VLs and we believe this was central to averting MTCT. Furthermore, meticulous organization of PLCS was undertaken, with clear instructions to all theatre staff on protocol such as avoiding breastfeeding at delivery.
Interplay between cultural beliefs (principally with regard to breastfeeding), religious beliefs (regarding blood products) and achieving desired clinical outcome compounded the complexity of the case. Breastfeeding is more widely practised among African women than among those from the UK. Failure to breastfeed may be viewed in some countries that the mother has HIV infection. 5 Consequently, this combined with factors such as financial pressures and maternal desire to breastfeed frequently act as barriers to bottle feeding. Although recent studies have demonstrated the benefits in extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission with the use of AZT/nevirapine, no studies have been performed in HIV-2 infection and the reduction in vertical transmission is not absolute. 6 Initially, our patient expressed a strong desire to breastfeed despite HIV-1/HIV-2/HBV infections. Under UK law, parents take proxy medical decisions for their children. 7 Parental rights are not absolute and may be legally overruled where the long-term health, safety or development of the child is compromised. 7 Previous Jehovah's Witness cases in the UK where parents challenged the medical decision to administer blood products were not upheld. 7 As happened, the baby did not require HBIG, although some Jehovah's Witnesses assert that some blood products including human immunoglobulin are permitted. 8
Our case underlines the importance of the availability of facilities and expertise for testing for proviral DNA in determining dual HIV-1 and HIV-2 infection. Co-infection with HIV-1 and -2 is rare but must be considered in patients of west African origins. The case highlights the importance of full awareness of the cultural and religious beliefs, ideas and expectations of expectant HIV-positive mothers in terms of birthing plan and future postnatal care plans for the baby so that appropriate counselling may be undertaken and careful planning by clinicians to minimize the risk of MTCT.