Preventive measures to avoid vertical transmission in untreated pregnant women with HIV/AIDS

Abstract

The HIV/AIDS during pregnancy has high morbidity and mortality, without optimal prevention and treatment. The advanced stage cases are found in developing countries due to late detection, but, also in developed countries due to immigration; therefore, the professionals should know the management steps for these patients. The implementation of specific interventions can reduce vertical transmission incidence until 1%–8%. It is presented a case of a pregnant woman with AIDS detected during first hospitalisation, due to a ventilatory failure by opportunistic germs; at the delivery the specific interventions were implemented, being able to eliminate vertical transmission to the newborn. This article explains the four main aspects to be considered for reducing vertical transmission (detection of HIV, viral load levels-CD4 lymphocyte count, way and moment of childbirth and antiretroviral therapy) and shares experiences of the management of an advanced case, in order to help professionals to handle these cases and its complications.

Background

Human Immunodeficiency Virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) are caused by the presence of HIV. Advanced stage is defined by CD4 lymphocytes <0.35×10⁹/L (350 cells/mm³) and a severe case (AIDS) with CD4 <0.2×10⁹/L (200 cells/mm³) or by the concomitance of opportunistic infections.¹

HIV/AIDS has high morbidity and mortality. Approximately 32.2–38.8 million HIV cases have been reported, with an incidence between 1.9 and 2.7 million and a mortality due to AIDS in 1.4–1.9 million. The advanced stage and high mortality are seen in developing countries, where the access to health services is difficult or limited, but, in developed countries it could be observed due to the problem of immigration. For 2013 the incidence of HIV has decreased by 25% compared with 2005, due to the implementation of promotion and prevention programs.^{1 2}

In Colombia 14 501 cases were reported in 2018, with a current rate of 29.1 patients with HIV per 100 000 habitants. Regarding pregnant women, 279 cases of HIV were identified, corresponding to 1.9% of all cases. Additionally, vertical transmission was reported in 0.3% of cases notified.³

Moreover, it is considered that with appropriate intervention the vertical transmission could be low down up to 1%–2%.^{1 4–6} Therefore, it is important to review this topic to enhance the knowledge regarding the impact of HIV and to clarify the main interventions to be conducted to prevent vertical transmission. It is presented the clinical case of a patient who was diagnosed with untreated AIDS during pregnancy.

Case presentation

The study patient, in early forties, in her fifth pregnancy with 25.3 weeks, was admitted with 2 months of dyspnoea. The patient had the following vital signs and findings on admission, normal heart rate and blood pressure, desaturation of 79% with FiO₂ at 21%, evidence of left lung-basal crepitus, a gravid uterus and a normal fetal heart rate. Subsequently, the patient developed ventilatory failure needing invasive mechanical ventilatory support, with subsequent distributive shock requiring vasopressor and inotropic treatment.

Investigations

Based on CT chest findings of a multilobar consolidative process with areas of frosted glass, pulmonary oedema versus infection by opportunistic germs was suspected and HIV test were requested.

Despite the maternal clinical deterioration, pregnancy progressed appropriately with fetal growth >50% percentile, estimated fetal weight was >500 g with adequate fetal well-being. On the other hand, the rapid HIV test and Enzyme-Linked ImmunoSorbent Assay (ELISA) fourth-generation confirmatory test were positive, with a viral load of 473 503 copies/mL, CD4 of 17.3% or 0.0096×10⁹/L (9.62 cells/mm³); therefore, it was considered a stage 3C HIV/AIDS.

Treatment

After 9 days of hospitalisation, at 26.4 weeks of pregnancy thrombocytopenia (69 000) associated to high proteinuria (825 mg/24 hours) was observed. Therefore, it was considered a possible HELLP syndrome (Hemolysis, Elevated Liver Enzymes and Low Platelets) and the Multidisciplinary Medical Board defined the need to do caesarean section.

Caesarean section was performed 12 days after hospitalisation at 27 week of pregnancy; therefore, fetal neuroprotection with magnesium sulphate and maternal peripartum antiretroviral prophylaxis was initiated with intravenous zidovudine in a bolus of 2 mg/kg in 1 hour and then 1 mg/kg/hour until the procedure was completed. The surgical procedure was performed without complications obtaining a newborn who required four-cycle cardiac massage, and orotracheal intubation. The newborn remained in a neonatal unit for 49 days with adequate clinical progress, with prophylaxis with Nevirapine 8 mg at 0-48-96 hours orally and Zidovudine for 6 weeks; negative HIV results were obtained with two negative viral load tests.

Outcome and follow-up

The patient continued with progressive deterioration, at 49 days after hospitalisation and 37 days postoperative, the patient had a cardiorespiratory arrest, where advanced resuscitation manoeuvres were performed without response.

Discussion

Vertical transmission continues to occur despite advances in coverage of prevention programs.⁷ The main limiting factor is the lack of knowledge of the status of the disease prior to gestation. In 2018, in England only one-third of pregnant women undergo a prenatal screening for HIV, and in Canada for 2014, HIV, and 26% of pregnant women who had HIV were not aware of the status of their disease.^6–8 In the case reported, the status of the disease was not known prior to gestation. Therefore, it highlights the management and strategic interventions used to decrease maternal–fetal transmission.

The main objective of the follow-up and care of pregnant women with HIV is to prevent vertical transmission.^{1 5} Management intervention parameters have shown a decrease in vertical transmission up to 1%–2%, and in Americas and the Caribbean decreasing from 15% to 8%.1 4 5 9 The measures that lower the risk of vertical transmission are shown in figure 1 and it is recommended to take into account four fundamental pillars to enhance the management.

Figure 1.

The measures that lower the risk of vertical transmission. Based on: Ministerio de Salud y Protección social¹, The American College of Obstetricians and Gynecologists,⁴ Ministerio de Salud y Protección Social,⁵ Money et al,⁶ British HIV Association,⁷ Chetty et al,⁸ Roig et al ¹⁰ and Peters et al.¹² ART, antiretroviral therapy.

The first pillar is the early diagnosis of HIV. It establishes the starting point for the implementation and initiation of antiretroviral treatment. All pregnant women should be screened to achieve a timely diagnosis.¹ The main tools for diagnosis are ELISA tests (immunoassay), rapid tests and western blot for ambivalent results.^{1 4} In the clinical case, the patient did not undergo HIV screening during the first trimester; therefore, the diagnosis and its stage were not known.

The second pillar is the determination of the viral load and the CD4 lymphocyte count, which help to determine the stage of the disease. The management guidelines state that the viral load value should be less or equal to 1000 copies/mL and the CD4 lymphocyte count greater than 200 cells/mm³ to reduce the risk of vertical transmission.^{1 4 5} A high viral load (473 503 copies/mL) was obtained in the patient, with T lymphocyte values of 0.026×10⁹/L (26 cells/mm³) and CD4 of 0.0096×10⁹/L (9.62 cells/mm³). The patient was classified to have AIDS with a high risk of maternal-fetal transmission.

Additionally, viral load is considered useful in determining the prognosis and the response to treatment.¹ Verifying the virological and immunological status each 4–8 weeks after starting antiretroviral therapy is recommended.⁶ Moreover, it is important to assess the viral load of the new-born at 4 weeks and 3–4 months after birth. HIV infection is excluded if there are two negative virological tests.⁶ The newborn in the case had two negative viral load tests; therefore, it was considered that vertical transmission prevention measures were effective.

The third pillar is the determination of the route and the moment of delivery. The viral load results of week 34–36 will define the route and time of delivery to prevent complications. Approximately 60%–75% of cases of vertical transmission occur during labour and delivery.^{4 10} Therefore, elective caesarean section is indicated before the onset of labour or at 38 weeks’ gestation in pregnant women with a viral load >1000 copies/mL or who have not received antiretroviral treatment or with zidovudine monotherapy.^{4 6} Accordingly, caesarean section was indicated in the study patient considering the high viral load and the absence of antiretroviral treatment.

Under the case of a patient with rupture of membrane, the patients with no antepartum or intrapartum antiviral therapy or under monotherapy, prolonged rupture (≥4 hours), viral load >1000 copies/mL or chorioamnionitis have higher risk of vertical transmission. If the pregnancy is >34 weeks it is recommended to decide the delivery route depending on maternal condition, antiretroviral treatment, duration of the rupture, but overall based on the viral load. Vaginal partum its allowed when <50 copies/mL, caesarean should be considered between 50 and 999 copies/mL and immediate caesarean should be done if >1000 copies/mL. For <34 weeks, it is controversial, and each case should be evaluated separately by considering the risk of prematurity and vertical transmission. In this case, the risk can be reduced if the mother has combined antiretroviral treatment at the time of the rupture.^{7 11–13}

The fourth pillar is antiretroviral therapy (ART) management, which aims to reduce viral load by interrupting viral replication.⁸ ART should be initiated as soon as the diagnosis is made.^{1 5–7} There are three stages known of ART to guide each case (see table 1). A reduction from 25% (no antiretroviral treatment) to 2% in the vertical transmission is shown by the implementation of these stages.⁶

Table 1.

Stages of antiretroviral therapy in pregnant women with HIV/AIDS

Moment	Objective
Pregnancy	Decrease maternal viral load
Intrapartum	Ensure antiretroviral prophylaxis prior to exposure to maternal fluids by the newborn
Postpartum	Give prophylaxis to the new-born and continue maternal treatment to reduce risk of disease’s evolution, independently of breastfeeding

Based on: Money et al.⁶

Initiating ART in pregnant women with HIV/AIDS is recommended regardless of the maternal viral load, and ideally between weeks 12 and 14.^{1 10} However, in 2018 the British HIV/AIDS Association recommended not to initiate ART until the second trimester unless the viral load is >100 000 copies/mL or the CD4 lymphocyte count is < 0.2×10⁹/L (200 cells/mm³).⁸ In the patient studied there were several indications for the initiation of ART^{1 6 7}; however, there were done other interventions with intrapartum antiretroviral management due to the critical health state of the patient.

Intrapartum management involves the administration of intravenous zidovudine. It should be started at a dose of 2 mg/kg in 1 hour followed by the infusion of 1 mg/kg/hour for the next 2 hours, to obtain adequate maternal-foetal blood concentrations.⁴

This management is followed by prophylaxis of the newborn, which must be started between 6 and 12 hours of birth at a dose of 2 mg/kg of Zidovudine every 6 hours orally for 6 weeks.^{5 6} However, the Canadian guide recommend that if the maternal viral load is >1000 copies/mL or the mother has not received treatment during gestation, Zidovudine should be administered for 6 weeks associated with three doses of Nevirapine in the first week plus Lamivudine twice a week.⁶ In the case reported, the newborn was administered zidovudine for 6 weeks and three doses of Nevirapine, with adequate tolerance and effective prophylaxis.

By last in the postpartum, the breastfeeding is one of the ways of vertical transmission, the risk increased 0.16% per each month of breastfeeding. The main factors that increased the vertical transmission via breastfeeding are a detectable HIV viral load, an advanced maternal HIV disease, long breastfeeding, injuries or inflammation in the breast, nipples or child’s mouth, preterm babies and mixed feeding.^{7 14} It is only recommended if the mother has <50 copies/mL viral load minimum in the last trimester and she is under combined antiviral treatment with good adherence. The mother and the baby should do a monthly viral load test until 2 months after the breastfeeding is stopped, if this is not possible it is recommended to avoid breastfeeding.^{7 14}

Learning points.

• Universal screening is essential in pregnant women, for adequate and timely treatment and it should be remembered that HIV cases in all its stages are appearing despite the prevention and promotion programs.

• Prevention, screening and education programs should continue to be promoted to prevent such cases.

• The measured to avoid vertical transmission are effective and they should be considered in the cases of HIV positive.

• The fourth pillar of the management in order to reduce vertical transmission are: early diagnosis of HIV, determination of the viral load and the CD4 lymphocyte count, determination of the route and the moment of delivery and the antiretroviral therapy management.

• It must continue active education of pregnant women, family members and healthcare personnel to increase knowledge about HIV/AIDS, the treatment possibilities and the prognosis, thus promoting the awareness regarding early detection.

• It is considered that preconceptional evaluation should be discuss carefully as it is possible to guarantee adequate management of pregnancy in patients with HIV.