If HIV-positive pregnant women were without any intervention, the rate of HIV transmission from mother to child could range from 14% to 48%, and the transmission of HIV from mother to child could occur in utero and in the intrapartum and postpartum period through breastfeeding. In China, a pilot project for the prevention of mother-to-child transmission (PMTCT) of HIV was initiated in 2001. For PMTCT of HIV, the Chinese government has released versions of guidelines since 2004, and the rate of mother-to-child transmission (MTCT) of HIV has decreased from 34.8% before 2005 to 3.6% in 2020 over the years.
In 2014, the World Health Organization (WHO) released guidance on global processes and criteria for the validation of elimination of mother-to-child transmission (EMTCT) of HIV and syphilis. For HIV, the minimum EMTCT impact targets are ≤50 new pediatric infections per 100,000 live births, and the transmission rate is <5% in breastfeeding populations or <2% in nonbreastfeeding populations, maintained for at least 1 year. In June 2015, Cuba became the first country in the world to be certified by the WHO for EMTCT of HIV. Subsequently, Thailand, Belarus, Armenia, and several other countries were certified.
In 2017, a pilot project for EMTCT of HIV, Syphilis, and Hepatitis B was launched by the Chinese government in Zhejiang, Guangdong, and Yunnan Provinces. Three years have passed since the pilot project and 5 years since the updated guideline for PMTCT of HIV, Syphilis, and Hepatitis B in 2015 (briefly as Guideline-2015). To promote EMTCT and further standardize the national PMTCT intervention, the Chinese government updated the guidelines for PMTCT of HIV, syphilis, and hepatitis B virus in 2020 (briefly as Guideline-2020). Here, we recommended the HIV guideline and discussed the updated points compared with the Guideline-2015.
2. Introduction to the Guideline-2020
The general goal of Guideline-2020 is to reduce the MTCT of HIV, try to avoid children infected by HIV from their mothers, and improve the health-related quality of life of HIV-positive women and their children. Figure 1 shows an overview of the PMTCT of HIV.
The HIV testing rate for pregnant women should be greater than 95%, the rate during pregnancy should be greater than 90%, and the rate during the first trimester should be greater than 70% whereas the rate was required to increase in the Guideline-2015.
Greater than 95% of HIV-positive pregnant women and more than 95% of children born to HIV-positive women should receive antiretroviral (ARV) therapy/prophylaxis. The rates set in the Guideline-2015 were both higher than 5%.
The rate of the MTCT of HIV should drop to less than 3%, whereas the rate was required to drop to less than 5% in the Guideline-2015.
The interventions for the PMTCT of HIV are based on women, maternal, and child health care, which cover health education and promotion, testing and counseling services for pregnant women, health care services and comprehensive care for HIV-positive pregnant women and their children, and intervention services.
2.2.1. Health education and promotion
To help women who are pregnant, breastfeeding, and planning to get pregnant to improve their knowledge and cognition in PMTCT of HIV, different kinds of health education and promotion campaigns should be carried out during the process of premarital, prepregnancy, maternal, child, youth, and community public health care, as well as venereal disease prevention and control.
2.2.2. Testing and consultation services for pregnant women
HIV testing and counseling services should be provided for all pregnant women to determine their HIV status. During the first antenatal care (ANC), information about HIV and PMTCT of HIV should be provided, whereas HIV antibodies should be tested. For those who are in high AIDS-endemic areas and are at high risk of HIV, HIV antibodies should be tested again in the third trimester. For pregnant women seeking maternal health services during labor, HIV antibodies should be tested by 2 reagents from 2 different manufacturers or 2 reagents on 2 different principles as soon as possible, and the result must come out in 30 minutes. The Guideline-2015 set the regulation that HIV antibodies should be tested by 2 different reagents for pregnant women seeking maternal health services during labor, and no time limit is required for the result. In principle, parturient women unaware of their HIV status before delivery should be treated medically for safety.
The HIV test procedure consists of a preliminary screening test and a reinspection test. If the results of the preliminary screening test are positive, reinspection should be performed. If reinspection is positive, a supplemental test should be performed as soon as possible [Figure 2].
HIV testing methods for pregnant women include HIV antibodies and supplementary tests. HIV antibody tests include immunoagglutination, immunochromatography, immunofiltration, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and antibody-antigen combined detection test. Supplemental tests include antibody confirmation and nucleic acid–based tests (NATs). Antibody confirmation tests include Western blotting, band/linear immunoassay, immunochromatography, immunofiltration, and replacement tests under certain conditions. The NAT includes qualitative and quantitative tests.
2.2.3. Health care services for HIV-positive pregnant women and their children
HIV-positive pregnant women should be offered standardized health care services during pregnancy and labor, according to 5 strategies for maternal-infant safety. Then, the HIV-positive pregnant women will be classified as “purple” risk according to the “5 colors” classification management. HIV-positive pregnant women should be followed up during the entire pregnancy, and their spouses/sexual partners should be mobilized for HIV testing. Natural labor is advocated, and after delivery, contraceptive guidance and counseling should be offered to help HIV-positive pregnant women make family planning, reduce unintended pregnancies, and prevent contagion.
Comprehensive care services, including health consultations and psychological and social support, are offered to HIV-positive pregnant women and their families, which are based on the self-rights and personal privacy.
2.2.4. Intervention services for the PMTCT of HIV
Antiviral therapy (ART) regimens for HIV-positive pregnant women are updated in the Guideline-2020, referring to the latest edition of the Technical Guidance for the PMTCT of HIV and National Guidance for Free Treatment of Antiviral Drugs for HIV/AIDS. Antiretrovirals are free for HIV-positive pregnant women and their children for the PMTCT of HIV.
(1) Antiviral therapy for pregnant women
For pregnant women, ARVs should be offered immediately if the HIV antibody test results are positive. The following regimens are recommended:
Regimen 1: Zidovudine (AZT)–lamivudine (3TC)–lopinavir/ritonavir (LPV/r)
Regimen 2: Tenofovir (TDF)–3TC–efavirenz (EFV)
Regimen 3: TDF, 3TC, and LPV/r
Note: The Guideline-2015 offers regimens 1 and 2 for preference.
For HIV-positive pregnant women who have received ARVs before pregnancy, the inhibition efficacy for HIV should be evaluated according to the results of the viral load (VL). If the VL is less than 50 copies/mL, the original ART regimen is continued. Otherwise, the ART regimen should be adjusted according to the original regimen.
If feasible, TDF-3TC/emtricitabine-integrase inhibitors are recommended for pregnant women who tested HIV-positive in the third trimester.
Note: After childbirth, HIV-positive women should continue to receive ART. When the hemoglobin level of pregnant women is lower than 90 g/L or the neutrophil count is lower than 0.75 × 109/L, it is not recommended to choose or continue AZT. Renal function assessment is required before TDF. Integrase inhibitors can be used if they are suitable for pregnant women.
Before ART, VL, CD4+ T lymphocyte count, and other relevant indicators, including blood routine, urine routine, liver function, renal function, blood lipid, and blood glucose, should be tested. During pregnancy on ART, CD4+ T lymphocyte count and other relevant indicators (same as before) should be tested again. HIV VL should be tested during the third trimester to assess AIDS progression and the risk to infants. An HIV resistance test is recommended before and on ART if conditional.
(2) Safe labor and delivery practices
HIV infection is not an independent indication for cesarean delivery. In particular, pregnant women on ART before the second trimester without AIDS clinical symptoms or with HIV RNA ≤1000 copies/mL during the third trimester or labor are not recommended for cesarean delivery.
Invasive manipulation, such as episiotomy, amniotomy, internal fetal monitoring, and forceps or vacuum devices, should be avoided as much as possible during ANC and labor. During labor, care measures should be provided to reduce the opportunity and time of contact with the mother's blood, amniotic fluid, and secretions as much as possible.
According to the mothers' ART regimen and laboratory test results, the infants could be classified as high-risk or low-risk HIV-exposed for ascertainment of ARV prophylaxis. Infants who meet one of the following conditions are classified as high-risk HIV-exposed, whereas the others are classified as low-risk HIV-exposed.
- HIV VL of their mothers during the trimester is >50 copies/mL.
- HIV VL of their mothers during the trimester is unknown, and the duration of ART is less than 12 weeks during pregnancy.
- HIV preliminary screening test of their mothers during labor or after delivery is positive.
Infants are not required to class according to their exposure risk in the Guideline-2015. Antiretroviral prophylaxis for all infants is AZT or nevirapine (NVP).
(3) Policy and practices for feeding
Mothers have a final choice of whether to breastfeed, and medical workers offer advice to mothers and their families on feeding patterns. Their advice is based on their cognition of mothers' knowledge and skills of feeding, acceptability, and affordability for breastfeeding or nonbreastfeeding to ensure that infants can achieve a healthy diet and adequate nutrition.
For breastfeeding infants, medical workers should offer consultation services for ARVs, breastfeeding methods, and ways to manage the breast. In the Guideline-2015, advice that breastfeeding should not last for 6 months and change to no breastfeeding as soon as possible is offered to the mother.
For nonbreastfeeding, medical workers offer mothers and their families guidelines on blending milk powder and sterilizing bottles.
(4) ARV prophylaxis for infants
All infants born to HIV-positive mothers should be offered ARV prophylaxis as early as possible, within 6 hours after birth. The ARV prophylaxis regimens for infants with low exposure risk to HIV were AZT or NVP for 4 weeks [Table 1].
Table 1 -
ARV prophylaxis regimen for infants at low exposure risk to HIV
|ARV prophylaxis regimen
||Birth weight (g)
||Doses of ARVs
||Duration of ARVs
||15 mg (suspension 1.5 mL), once per day
||Within 6 hours after birth, for 4 weeks
|<2500 and ≥2000
||10 mg (suspension 1.0 mL), once per day
||2 mg/kg (suspension 0.2 mL/kg), once per day
||15 mg (suspension 1.5 mL), twice per day
||Within 6 hours after birth, for 4 weeks
|<2500 and ≥2000
||10 mg (suspension 1.0 mL), twice per day
||2 mg/kg (suspension 0.2 mL/kg), twice per day
ARV: Antiretroviral; AZT: Azidothymidine; NVP: Nevirapine.
Antiretroviral prophylaxis should be offered for infants with high exposure risk to HIV, with a regimen of AZT-3TC-NVP/LPV/r twice per day for 6 weeks. The doses are adjusted according to gestational age at birth, infant age, and infant body weight [Table 2].
Table 2 -
The doses of ARV prophylaxis for infants at high exposure risk to HIV
|Birth weight (kg)
|Gestational age at birth <35 weeks
|Gestational age at birth ≥35 weeks
—: Not applicable; 3TC: Lamivudine; ARV: Antiretroviral; AZT: Azidothymidine; LPV/r: Lopinavir/ritonavir; NVP: Nevirapine.
Therefore, the adverse effects of ARVs in infants should be monitored in a timely manner. For children at high exposure risk to HIV, routine blood, liver, and renal function tests should be performed at 2 and 4 weeks after ARVs. If adverse effects are detected, the corresponding measures for children should be taken by a doctor.
(5) HIV testing for infants born to HIV-positive mothers
All infants born to HIV-positive mothers should be followed up at 1, 3, 6, 9 (8), 12, and 18 months. A physical examination should also be performed. Testing for early infant diagnosis (EID) of HIV involves a NAT within 48 hours after birth, at 6 weeks, and 3 months, and the testing within 48 hours after birth is added in the Guideline-2020. HIV infection status is confirmed if 2 results are both positive. Infants with NAT negative for EID or without EID should be tested for HIV antibodies at the age of 12 months, and the negative result indicates that the infant is not HIV-infected. Those with positive antibodies should be tested for HIV antibodies again at the age of 18 months. If the antibody test is also positive, supplementary tests should be performed to confirm whether the child is infected with HIV.
Figure 3 shows the testing strategy.
2.3. Support measures
2.3.1. Service capacity
The service system, norms, and procedures for the PMTCT of HIV should be improved, whereas the collaboration between regions and institutions should be strengthened.
A long-term training mechanism should be established to build an expert and trainer team and train PMTCT management and service personnel.
The laboratory for HIV testing should be strictly constructed and managed to strictly control testing quality and ensure timely access to test results. Additionally, regional laboratory testing networks should be improved to promote the participation of community organizations in the PMTCT of HIV.
2.3.2. Capital and material management
Drugs, equipment, and other materials are timely bids for procurement, meeting requirements, as well as avoiding waste and out-of-stock.
The capital for the PMTCT should be strictly managed, ensuring that capital from the national programs is used for HIV testing, comprehensive intervention, follow-up, and management.
2.3.3. Direction and evaluation
Directions and evaluation systems for the PMTCT of HIV should be established. The Department of Maternal and Child Health of the National Health Commission (NHC) of China organizes experts to conduct on-site guidance and evaluation. The health administration department in the local government should formulate guidance and evaluation plans for the PMTCT of HIV locally, refine evaluation indicators, organize and carry out evaluations regularly, and submit work reports to the higher administrative departments in a timely manner.
2.4. Duties and cooperating of departments
2.4.1. Duty of health administration department
The Department of Maternal and Child Health of the NHC is responsible for the organization, coordination, and management of the national PMTCT of HIV in China. The Bureau of Medical Administration and Department of Maternal and Child Health of the NHC are responsible for the management and coordination of diagnosis and treatment of HIV-positive pregnant women and their children. The Bureau of Disease Prevention and Control of the NHC is responsible for monitoring the epidemic of HIV nationwide. The health administration department of the local government is responsible for the organization, coordination, and management of the PMTCT of HIV.
2.4.2. Medical institutions
The National Center for Women and Children's Health, Chinese Center for Disease Control and Prevention, is entrusted by the Department of Maternal and Child Health of the NHC to provide technical support for the national PMTCT of HIV, provide professional guidance and professional staff training, and promote appropriate technologies. Maternal and child health institution levels should be responsible for the technical guidance and services for the PMTCT of HIV locally and assist the health administrative departments in the management of PMTCT of HIV.
General hospital/infectious disease specialist hospitals provide testing and consulting services for the PMTCT of HIV for pregnant women, provide standardized intervention services for HIV-positive pregnant women and their children, and collect and report relevant information and data.
Disease prevention and control institution levels are responsible for monitoring the epidemic of HIV locally and responsible for the quality management of laboratories with the clinical testing centers, timely exchange of data and information with maternal and child health institutions, publicity, training, technical guidance for the PMTCT of HIV, and cooperation with the diagnosis, treatment, and referral services of HIV-positive pregnant women and their children.
2.5. Definition indicators for PMTCT of HIV and corresponding calculation formulas
In the Guideline-2020, indicators for the PMTCT of HIV and corresponding calculation formulas are defined.
2.5.1. HIV testing rate for pregnant women and puerpera
Definition: Percentage of pregnant women and puerpera tested for HIV
Numerator: Number of pregnant and puerperae tested for HIV during pregnancy and/or labor
Denominator: Total number of puerperae
2.5.2. HIV testing rate during pregnancy
Definition: Percentage of pregnant women tested for HIV at least once during pregnancy
Numerator: Number of pregnant women tested for HIV during pregnancy
Denominator: Total number of puerperae
2.5.3. HIV testing rate during the first trimester
Definition: Percentage of pregnant women tested for HIV at least once during the first trimester
Numerator: Number of pregnant women tested for HIV during the first trimester
Denominator: Total number of puerperae
2.5.4. ARV rate in HIV-positive pregnant women
Definition: Proportion of HIV-positive pregnant women who received ARVs
Numerators: Number of HIV-positive pregnant women who received ARVs during pregnancy and labor
Denominator: Number of HIV-positive puerperae
2.5.5. ARV rate of infants born to HIV-positive mothers
Definition: Proportion of infants on ARVs born to HIV-positive mothers
Numerator: Number of infants born to HIV-positive mothers who receive ARVs
Denominator: Number of infants born to HIV-positive mothers
2.5.6. Rate of MTCT of HIV
Definition: Proportion of children born to HIV-positive mothers diagnosed with HIV at the age of 18 months
Rate of MTCT of HIV = (A plus B plus annual death correction coefficient × C) / (D plus E)
where A is the number of surviving children at least 18 months old born to HIV-positive mothers whose HIV antibody tests are positive; B is the mortality of children at least 18 months old who are HIV-positive with EID; C is the number of children at least 18 months old born to HIV-positive mothers who have not received EID or whose result of EID is unknown; D is the number of children tested for HIV antibodies at 18 months of age among the surviving children; and E is the mortality of children at least 18 months old born to HIV-positive mothers.
From the previous Guideline for the PMTCT of HIV, Syphilis, and Hepatitis B in China released in 2015, new research results and fresh ideas have come out worldwide.[6–9] Based on the first edition of the global guidance on criteria and processes for validation, the elimination of MTCT of HIV and syphilis was released by the WHO in 2014. It was updated by the WHO, and the second edition was released in 2017. To promote the EMTCT of HIV, syphilis, and hepatitis B virus in China, the Chinese government updated the Guideline for the PMTCT of HIV, Syphilis, and Hepatitis B in 2020. Compared with the Guideline-2015, the goals, health education and promotion, procedure of HIV testing for pregnant women, ART regimen for HIV-positive pregnant women, and ARV prophylaxis regimen for infants are updated in the Guideline-2020.
The rate of MTCT of HIV is set to less than 3% compared with less than 5% in the Guideline-2015, which is less than 5% in breastfeeding populations and more than 2% in the nonbreastfeeding populations. The rate is set to less than 3% because breastfeeding and nonbreastfeeding populations coexist in different areas in China, and breastfeeding could increase the risk of MTCT of HIV.
Antiviral therapy for HIV-positive pregnant women as early as possible could reduce the risk of MTCT of HIV further.[13,14] Pregnant women are expected to know their HIV status as early as possible. In 2016, 49.2% of pregnant women received HIV testing during the first trimester in Yunnan province, and 61.87% received the first ANC during the first trimester in 8 provinces in China in 2018. In the Guideline-2020, the HIV testing rate during the first trimester was defined as 70% according to expert consensus, which is not defined in the Guideline-2015, and the ART rate for HIV-positive pregnant women and phylactic ARV rates for infants were both set to 95%, increasing by 5% compared with the Guideline-2015.
Another key point updated in the Guideline-2020 is the ART regimen for HIV-positive pregnant women. For HIV-positive pregnant women, the third ART regimen, TDF-3TC-LPV/r, is recommended in the Guideline-2020 based on the regimens with AZT-3TC-LPV/r or TDF-3TC-EFV in the Guideline-2015. Tenofovir and 3TC are nucleoside reverse transcriptase inhibitors, and LPV/r is a combination of HIV medicines. In China, the regimen with TDF-3TC-LPV/r was efficacious as a second-line regimen with acceptable nephrotoxicity profiles if AZT or stavudine failed in patients. For pregnant women who tested positive for HIV in the third trimester, another regimen with 3 nucleoside reverse transcriptase inhibitors and an integrase inhibitor is recommended. The regimen comprises TDF, 3TC, emtricitabine, and an integrase inhibitor, which can block HIV integrase, an enzyme that HIV needs to make copies of itself.
Antiviral therapy prophylaxis for infants is also updated in the Guideline-2020. New evidence shows that triple ARV neonatal prophylaxis with AZT/3TC/NVP for 6 weeks in high-risk HIV-exposed infants did not significantly increase the risk of short-term toxicity compared with AZT monotherapy prophylaxis. In the British recommendation, combination ARVs for infants born to HIV-positive pregnant women were released in the guideline. In the Guideline-2020, the ARV prophylaxis recommendations for high-risk HIV-exposed infants are as follows: AZT-3TC-NVP/LPV/r twice per day for 6 weeks, whereas AZT or NVP is for infants whose mothers are on ART during labor or after delivery for 6 to 12 weeks in the Guideline-2015; meanwhile, the doses of ARV prophylaxis suggested for infants at high exposure risk to HIV should be adjusted according to gestational age at birth, infant age, and body weight of the infant. The duration of ARV prophylaxis for infants at low exposure risk to HIV is 4 weeks compared with 4 to 6 weeks in the Guideline-2015. All points updated above are applicable to infants.
The authors thank the Department of Maternal and Child Health of the NHC of People's Republic of China for directing the Guideline's updates.
Ailing Wang designed all aspects of the study. Shuiling Qu wrote the first draft of the manuscript. Qian Wang, Xiaoyan Wang, Yaping Qiao, Jun Yao, Zhen Li, Xi Jin and Zhixin Li participated in discussion and revised the manuscript. All authors read and approved the final manuscript.
Conflicts of Interest
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