F33 Women living with HIV

Introduction

Globally around half of the HIV-infected population comprises of women. In Hong Kong, women account for nearly 20% of the cumulative reported cases of HIV infection and AIDS since year 1984, and 15-20% of the new HIV or AIDS diagnoses every year.[1] While the clinical features and management of HIV infection in women are similar to that in men, there exist important issues that are unique to women living with HIV, and which require special considerations from physicians providing care to them.

Studies have shown that the HIV viral load was lower in women than in men during both primary and chronic stages of infection, after controlling for CD4 cell count. However, the time to the development of AIDS appeared to be similar.[2] In terms of mortality, women were found to have higher HIV-related mortality early in the epidemic, which was linked to the facts that women were more likely to have a delay in HIV diagnosis and reduced access to care.[3]

Antiretroviral therapy in women

The efficacy of antiretroviral therapy in women appears to be comparable to that in men in general, without significant differences observed in the virologic, immunologic and clinical outcomes. At the same time, though not clinically significant, women appear to be less tolerant of antiretroviral drugs than men. In practice, the recommended highly active antiretroviral therapy (HAART) for non-pregnant women with no plan to conceive are the same as those for the general HIV-infected population.[4] However, prior to initiation of HAART in women with childbearing potential, a pregnancy test should be performed and selection of the antiretroviral regimen should take into consideration the potential drug-drug interaction that might impair contraceptive efficacy. Special attention should also be made for women planning for pregnancy to ensure the health of both the mother and the foetus, and to minimise the risk of teratogenicity.

Family planning

Given a nearly normal life expectancy and good evidence to support a very low transmission risk to serodiscordant partner or foetus with the use of suppressive antiretroviral treatment, HIV infection should not be a barrier to healthy family life for women living with HIV. HIV infected women should have access to appropriate advice on contraception, conception and fertility, as well as specialised and multidisciplinary care throughout the course of pregnancy. Partners of HIV-infected women should be encouraged to undergo HIV testing if their HIV status is unknown.

Contraception

Women living with HIV who are of childbearing age but not planning for pregnancy should be offered contraceptive advice, so as to avoid unintended pregnancy or pregnancy termination. In general, consistent use of male condom in conjunction with an additional contraceptive method are advised for optimal contraception, and prevention of transmission of HIV and other sexually transmitted infections (STI). There is no major limitation to the various contraceptive methods (e.g. pills, injectables and intrauterine devices), and women living with HIV should be counselled similarly as non-infected women using the medical eligibility criteria in order to suggest a contraceptive method that is safe and acceptable.[5]

Several protease inhibitors (PI), efavirenz (EFV), and elvitegravir (EVG)/cobicistat(COBI)-based regimens, however, have clinically significant drug-drug interactions (DDI) with combined oral contraceptives that may either impair the contraceptive efficacy or increase the risk of oestrogen- or progestin-related adverse effects. Special consideration should therefore be made for women on HAART to avoid these DDI, and under such circumstances where alternative contraceptive methods are not available and reasonable antiretroviral alternatives exist, an antiretroviral switch may be warranted.

Pre-conception counselling

Comprehensive reproductive and sexual health counselling including pregnancy intention should be discussed with women of childbearing age on an ongoing basis throughout the course of their care. General advice including cessation of smoking, alcoholic and illicit drug use, and folic acid +/- vitamin D supplementation should be offered. Women living with HIV who are contemplating pregnancy should be commenced on HAART, and be advised to achieve sustained viral suppression prior to conception. In addition, serodiscordant couples planning for pregnancy should be offered advice on measures to prevent partner transmission of HIV, which include the use of antiretrovirals to maintain sustained viral suppression, screening and treating both partners for STI. These measures should be reinforced when the couples are attempting to conceive via condomless sex or self-insemination during the periovulatory period.[5][6]

Recommended antiretrovirals in pregnant women and non-pregnant women who are trying to conceive

The preferred 3-drug antiretroviral regimen in women with desire for pregnancy or who are pregnant include raltegravir (RAL) (twice daily dosing) or ritonavir boosted-PI (darunavir, DRV or atazanavir, ATV), together with a backbone using tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC)/lamivudine (3TC), or abacavir (ABC) + 3TC. HLA-B*5701 is rare in Chinese population but should be noted when considering ABC in other ethnic groups. Alternative antiretrovirals that may be considered include lopinavir-ritonavir (LPVr), EFV, rilpivirine (RPV), and backbone with zidovudine (ZDV)/3TC. Antiretrovirals which have potential concern for teratogenicity or adverse pregnancy outcomes should be avoided, which, as of to date, include dolutegravir (DTG), didanosine (ddI) and stavudine (d4T). In particular, DTG is not recommended for use in pregnant women during the first trimester and in non-pregnant women who are trying to conceive, due to concerns about a possible increased risk of neural tube defects in infants. Any COBI-boosted regimens (including ATV, DRV and EVG) are also not recommended due to concerns about pharmacokinetic changes in the second and third trimesters that may lower drug exposures with potential lead to virologic failure. There are currently insufficient safety or pharmacokinetics data to support the use of other newer ARVs like tenofovir alafenamide (TAF) and bictegravir (BIC) during pregnancy.[5][6]

Pregnancy Care[Algorithm 33][6][7]

Without any preventive measure, the rate of mother-to-child transmission (MTCT) of HIV is as high as 30-40%. Over the years, many interventions have been implemented in order to reduce the risk. Early diagnosis of HIV and the use of antiretroviral therapy during pregnancy and labour are crucial to the prevention of mother-to-child transmission (PMTCT) of HIV. Women who are diagnosed to have HIV infection antenatally should be started on HAART as soon as possible without waiting for the result of the genotypic resistance testing (GRT). Women on suppressive HAART at conception should continue their regimen unless there is any safety issue. Antiretrovirals with safety concern during pregnancy should be avoided (see section “Recommended antiretrovial drugs in pregnant women and non-pregnant women who are trying to conceive”). The viral load should be monitored closely thereafter, with the aim of bringing down the viral load to undetectable level before delivery. Due to changes in the pharmacokinetics during pregnancy, dosage increase is required in certain antiretrovirals. Changes in the antiretroviral regimen (e.g. switching or intensification) may be required in case of resistance mutations identified in GRT or suboptimal viral control.

HIV infection is not a contraindication to normal vaginal delivery in women who have achieved undetectable viral load before delivery. For women who fail to attain complete viral suppression before delivery, caesarean section which lowers the risk of HIV transmission should be considered. Intrapartum intravenous infusion of ZDV is vital for PMTCT in women whose viral load are still detectable near delivery, and in whom HIV infection are diagnosed at the onset of labour. Post-natally, antiretroviral prophylaxis will be provided to newborns while breastfeeding should be avoided, which are two important steps for PMTCT. All in all, multi-disciplinary care from HIV specialist, obstetricians, paediatricians and nurses etc. are central to the care of pregnant HIV-infected women. With the implementation of all the preventive measures, the overall rate of perinatal transmission of HIV has been reduced dramatically to 1% or less.

Prevention of mother-to-child transmission (MTCT) of HIV in Hong Kong

In Hong Kong, public health programme for antenatal HIV testing and local guidelines on clinical intervention are integral parts of preventing MTCT of HIV. The Universal Antenatal HIV Testing Programme (UATP) has been in place since September 2001. The programme was supplemented, since January 2008, with rapid HIV testing in labour wards of public hospitals to fill the gap for late-presenting pregnant women without documented HIV status in the antenatal period. On the other hand, Scientific Committee on AIDS and STI (SCAS) has laid down local clinical recommendations on the prevention of MTCT since 2001. The latest version was updated in November 2018.[HK Guidelines 33A]

UATP has been a well-accepted programme, with a coverage of over 97% among pregnant women attending public antenatal services since its establishment in 2001. When UATP is coupled with rapid HIV testing, the percentage of women with HIV test results available at delivery increased from less than 90% in 2006 to over 99% in the past decade.

As of the end of 2017, a total of 130 HIV positive pregnancies have been identified by UATP and rapid HIV testing. The number of termination of pregnancy procedures performed annually has ranged from zero to three cases. As of the end of 2017, three out of 84 children born to these HIV-infected mothers identified via the programme were confirmed HIV infected. All three positive cases were born before 2008 when rapid HIV testing was introduced, and were associated with late maternal HIV diagnosis and/or late intervention. Prompt HIV diagnosis and intervention is clearly the key to effective MTCT prevention of HIV.

Cervical cancer screening[5][8]

Women living with HIV are at increased risk of human papillomavirus (HPV) infections and associated cervical diseases (cancers and pre-cancers) as compared with the general population, and the risks are higher for those with more advanced immunosuppression (low CD4 count <200/μL). Also, they are more likely to present with multifocal diseases and have more rapid progression to cervical carcinoma. In the era of HAART, although there is an associated reduction in the burden of HPV infections, there is conflicting data about any reduction in the burden of HPV-related diseases, perhaps an effect due to the longer life expectancy that allows a longer persistence of HPV infections and the cumulative incidence of tumours over time. In general, more frequent cervical smear screening is advised for women living with HIV. Depending on the availability of high risk-HPV co-testing and genotyping for HPV 16/18, cervical smear should be performed every 1-3 years and any abnormal cytology should be referred for further investigation like colposcopy. The US Advisory Committee on Immunization Practices (ACIP) recommends vaccination against HPV in HIV-infected women and men aged 13 through 26, although it may be less immunogenic as compared to those without HIV, and in those who have low CD4 count.[9] The British HIV Association (BHIVA) has similar recommendations and also suggests that previously unvaccinated HIV-positive women aged up to 40 years be offered HPV vaccination, and that vaccination may be deferred in ART-naive patients with CD4 counts <200/μL until the patient is established on HAART.[10]

Menopause[5]

Given a longer life expectancy, more women living with HIV are now entering menopause. Very limited evidence showed that HIV infection may be associated with an earlier age of onset of menopause, and a higher rate of some of the menopausal symptoms like urogenital symptoms. The effect from oestrogen deficiency, together with the ageing effect and a variety of metabolic complications associated with HIV infection and antiretroviral treatment, cardiovascular diseases and osteoporosis are expected to be important health issues in post-menopausal women, which warrant special consideration from attending physicians. Any modifiable cardiovascular risk factor should be managed accordingly, and review on the fracture risk should be performed regularly. The management of post-menopausal HIV-infected women, including the use of hormone replacement therapy, are under-studied and more researches are required to inform the appropriate management for this group of patients. Other aspects of metabolic complications in HIV/AIDS are covered in Chapter C15.

Psychosocial aspects of HIV infection in women[5]

Women living with HIV are at risk for various social problems, including intimate partner violence, food / housing insecurity, social stigma and discrimination etc. They are also at risk for mental health problems including depression, post-traumatic stress disorder, alcohol or substance abuse. In particular, a new HIV diagnosis during pregnancy may precipitate a complex mix of emotional, social, economic and relationship issues. These psycho-social problems will lead to difficulty in adherence to HIV treatment, which in turn would have a negative impact on the physical health of patient and the pregnancy outcomes. As a result, healthcare providers should be alert for any potential psychological or social issue during their care for HIV-infected women, and to offer psychological and social support to those women in-need. This often requires a holistic approach from various parties, including psychiatrist, psychologist, nursing, social worker and peer support group. Psychosocial needs of PLWHA is addressed in Chapter A4.

References

Hong Kong Guidelines