INTRODUCTION — Most pediatric human immunodeficiency virus (HIV) infections result from vertical transmission of HIV, which can occur during pregnancy (in utero), at labor/delivery (perinatal), or postdelivery (postnatal) through breastfeeding. Although vertical transmission of HIV in resource-rich settings is rare, it continues to occur in resource-limited settings. However, efforts to increase the use of antiretroviral therapy (ART) and access to comprehensive HIV and pregnancy care services have led to a marked decrease in vertical HIV transmission rates in resource-limited settings .
This topic will address the epidemiology of vertical HIV transmission and present antiretroviral recommendations for pregnant individuals and their infants to prevent vertical transmission in resource-limited settings. This topic will also review the remaining barriers to total elimination of vertical transmission.
Information regarding the prevention of HIV transmission during breastfeeding (postnatal transmission) in resource-limited settings is found elsewhere. (See "Prevention of HIV transmission during breastfeeding in resource-limited settings".)
The management of pregnant individuals with HIV in resource-rich settings is discussed in detail elsewhere. (See "Prenatal evaluation of women with HIV in resource-rich settings" and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings" and "Intrapartum and postpartum management of pregnant women with HIV and infant prophylaxis in resource-rich settings".)
The safety and pharmacology of specific antiretroviral agents during pregnancy are discussed in detail elsewhere. (See "Safety and dosing of antiretroviral medications in pregnancy".)
Burden of disease — Surveillance data from the Joint United Nations Programme on HIV/acquired immunodeficiency syndrome (AIDS) over the past two decades have documented the heavy burden and impact of HIV on mothers and infants living in resource-limited settings [2,3]. Greater than 90 percent of all new pediatric HIV cases result from vertical transmission. Sub-Saharan Africa carries the greatest burden of the epidemic: 23 focus countries (all in sub-Saharan Africa except for Indonesia and India) account for 86 percent of pregnant individuals and 80 percent of children aged 0 to 14 years living with HIV . In 2020, there were an estimated 150,000 new infections in children worldwide. Over the past decade, there has been a rapid scale-up of services to prevent vertical HIV transmission [5,6]. In 2020, an estimated 85 percent of pregnant individuals with HIV received antiretroviral therapy (ART), approximately two-thirds of whom were receiving ART at the time of conception . Despite the expansion of ART availability, the majority of new pediatric infections were the result of mothers not receiving ART (31 percent), dropping off ART during pregnancy (14 percent), or mothers newly acquiring HIV infection during pregnancy (7 percent) or breastfeeding (16 percent) . (See 'Ongoing challenges' below.)
Risk of vertical HIV transmission — Without antiretroviral preventive interventions, the risk of vertical HIV transmission has varied between 15 and 45 percent, depending on maternal risk factors and whether breastfeeding is practiced . The most important risk factor for transmission has consistently been maternal plasma viral load. Acquisition of HIV during pregnancy or breastfeeding is associated with an especially high risk of transmission. Additional information on HIV acquisition during breastfeeding and risk of infant transmission is discussed elsewhere. (See "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Epidemiology of HIV transmission through breastfeeding'.)
●Maternal viral load – Multiple studies, including the original trial of zidovudine to prevent vertical transmission, have demonstrated a direct positive correlation between maternal plasma viral load and risk of transmission to the infant [10-15].
This correlation is observed also among pregnant individuals taking ART. As an example, in a study from the National French Perinatal Cohort including 14,630 infants born to pregnant women with HIV delivering between 2000 and 2017 at 90 centers in France, vertical transmission rates were lower among women with a viral load <50 copies/mL near delivery compared with women with higher viral loads (0 percent transmission versus 0.2 and 2.4 percent with viral load ranges 50 to 399 copies/mL and 400 copies/mL or higher, respectively) .
●Incident infection during pregnancy – Acute HIV infection during pregnancy is associated with higher vertical transmission risk, possibly due to the higher plasma viral loads seen in acute HIV infection. In a meta-analysis of 37 studies, which included over 100,000 person-years of follow up, the pooled incidence of HIV acquisition during pregnancy was 3.4 events per 100 person years . Studies prior to 2014 had higher HIV incidence rates compared with studies conducted after 2014.
Other maternal and infant factors have also been associated with increased risk of transmission. Some associated maternal risk factors include low CD4 cell counts, more advanced World Health Organization clinical disease stage, anemia, and sexually transmitted infections, although these factors often correlate with high maternal viral load [14,18].
Risk factors related to transmission during breastfeeding are discussed elsewhere. (See "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Risk factors for HIV transmission through breast milk'.)
Timing of vertical HIV transmission — In the absence of prevention interventions, most vertical transmission occurs during the third trimester or at the time of delivery.
In nonbreastfeeding settings prior to the availability of antiretroviral interventions, in utero infections (indicated by a positive HIV nucleic acid amplification test [NAAT] in the infant within 72 hours after birth) were estimated to account for about one-third of the infant HIV infections, while about two-thirds of transmissions were thought to have occurred around the time of labor and delivery (indicated by HIV NAAT results in the infant that were negative within the first 72 hours after birth, but then were positive by four to six weeks of age) .
In breastfeeding settings prior to the availability of antiretroviral interventions, about 25 to 40 percent of infant infections were estimated to occur in utero, about 50 percent around the time of labor/delivery or through very early breastfeeding, and the remainder during the breastfeeding period . (See "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Risk of HIV transmission through breast milk'.)
A majority of in utero transmission is thought to occur during the third trimester. This conclusion is based on low rates of viral detection using HIV NAAT on fetal tissue from abortions in the first and second trimester  as well as statistic modeling analyses . Additionally, in a study of long versus short antenatal zidovudine prophylaxis for prevention of vertical transmission, the rate of in utero transmission was 5.1 percent when starting zidovudine at 36 weeks gestation compared with 1.6 percent when starting zidovudine at 28 weeks gestation, suggesting that a significant proportion of transmission may occur between 28 to 36 weeks gestation, and a smaller residual amount of in utero infection may occur earlier in pregnancy .
Mechanisms of transmission
In utero — Mechanisms of transmission are thought to be related to breakdown of the integrity of the placenta, leading to microtransfusions of viremic maternal blood across the placenta to the fetus . A number of studies have shown that genital tract infections and placental inflammation, especially chorioamnionitis, can increase in utero HIV transmission .
Intrapartum — Transmission during the time of labor and delivery is postulated to occur through contact of infant mucosal membranes with HIV virus in blood and secretions during the birth process. In the absence of ART, duration of membrane rupture greater than four hours has been associated with increased risk of vertical transmission . In addition, microtransfusions across the placenta during labor contractions also likely contribute to the heightened risk of transmission during the labor and delivery period .
During breastfeeding — The mechanism of transmission of HIV during breastfeeding is discussed elsewhere. (See "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Mechanism of breast milk transmission'.)
OVERVIEW OF CARE TO PREVENT TRANSMISSION — Suppressive antiretroviral therapy (ART) is the cornerstone of strategies to prevent vertical transmission of HIV. However, the complete cascade of HIV services includes additional measures beyond simply administering antiretroviral agents. These include:
●Care for at-risk pregnant individuals without known HIV:
•Routine rapid HIV testing during the initial antenatal visit to identify individuals with HIV early during pregnancy.
•For those in serodiscordant relationships who test negative for HIV, counseling and discussion of HIV pre-exposure prophylaxis initiation is warranted.
•Repeat HIV testing during third trimester and/or at delivery for at-risk pregnant individuals without HIV who test negative earlier during pregnancy.
●Antenatal and perinatal care for pregnant individuals with HIV and their infants:
•Rapid initiation of effective lifelong ART at the time of diagnosis of HIV infection (see 'Maternal antiretroviral therapy' below)
•CD4 cell count screening and clinical assessment of immune status
•Scheduling regular antenatal visits during pregnancy for ART adherence counseling, ART drug refills, toxicity monitoring, and routine pregnancy care
•Delivery by a skilled birth attendant, preferably at a health facility (see 'Mode of delivery' below)
•Prompt initiation of postnatal antiretroviral prophylaxis for the infant (see 'Infant postnatal prophylaxis' below)
●Postpartum care for mothers with HIV and their infants:
•Continued management of lifelong ART
•Family planning and reproductive health services
•Counseling on infant feeding (promoting six months of exclusive breastfeeding) (see "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Options for infant feeding')
•Early infant HIV testing and return of results using nucleic acid amplification testing (see "Diagnostic testing for HIV infection in infants and children younger than 18 months", section on 'Mother with HIV')
•Ensuring referral and long-term linkage to HIV care and treatment as well as counseling for ART adherence for the mother
•For children determined to be infected with HIV, rapid referral to HIV care and treatment services for immediate initiation of ART
MATERNAL ANTIRETROVIRAL THERAPY
ART recommended for all — Antiretroviral therapy (ART) is recommended for all pregnant individuals with HIV, regardless of their CD4 cell count or disease stage, to reduce the risk of transmission to their infants and for their own clinical benefit . The goal of ART is to reduce the viral load to undetectable levels since the risk of HIV transmission decreases with the viral load. (See 'Risk of vertical HIV transmission' above.)
Individuals already on ART prior to pregnancy
●Virally suppressed on ART − Individuals already taking effective ART prior to pregnancy should generally continue the same regimen throughout pregnancy. In resource-limited settings, most individuals will be taking World Health Organization (WHO)-recommended first- or second-line ART regimens that have satisfactory safety data in pregnancy (eg, dolutegravir, protease inhibitors, lamivudine, tenofovir).
In the uncommon event that an adolescent or female living with HIV in a resource-limited setting is using an agent with limited data on use in pregnancy, the decision to continue the regimen with counseling on the benefits and uncertain risks versus switch to other drugs with more safety data available should be individualized. (See "Safety and dosing of antiretroviral medications in pregnancy".)
Individuals who are virally suppressed on ART prior to pregnancy have a low risk of transmitting HIV to their infant. As an example, in a study of 1142 pregnant women with HIV in South Africa, lower rates of transmission were observed among women who had initiated ART prior to pregnancy compared with during pregnancy (0.7 versus 5.7 percent) . In the French Perinatal Cohort, there were no vertical transmissions among 5482 pregnant women with HIV who initiated ART before conception, continued it throughout pregnancy, and had viral load <50 copies/mL at delivery .
●Not virally suppressed on ART – If an individual is taking ART but is not virally suppressed at the time of pregnancy, health care providers should provide counseling and implement enhanced adherence interventions to try to achieve viral suppression as quickly as possible. If viral suppression is not achieved within eight weeks following these interventions, the individual should be switched to the next-in-line ART regimen according to the local and/or national guidelines. These individuals should receive frequent viral load monitoring throughout their pregnancy.
Individuals not on ART prior to pregnancy — A lifelong ART regimen should be initiated in all pregnant individuals as soon as HIV is diagnosed. The WHO recommends dolutegravir, tenofovir disoproxil fumarate (TDF), and lamivudine (or emtricitabine) as the preferred first-line regimen for the treatment of HIV infection in adults and adolescents, including pregnant individuals . Choice of second- and third-line regimens is the same as for nonpregnant adults and is discussed further elsewhere. (See "Use and impact of antiretroviral therapy for HIV infection in resource-limited settings", section on 'Regimen selection'.)
Maternal ART is the most important factor for reducing HIV transmission to the infant, overriding other clinical, virologic, and immunologic risk factors. Early initiation of ART with sustained viral suppression provides maximal protection against transmission [28-31]. Among 730 pregnant women with HIV in South Africa who initiated ART during pregnancy, each additional week of ART during pregnancy reduced odds of transmission by 8 percent . The efficacy of combination ART in reducing vertical transmission has also been demonstrated in several trials and observational studies in resource-limited settings [30-39]. In these studies, ART was associated with vertical transmission rates at birth and in the early postpartum period of less than 1 to 5 percent, depending on adherence rates among each study population; these rates are comparable to the low transmission rates achieved with ART in pregnant females with HIV in resource-rich settings.
Dolutegravir-containing ART regimens are associated with good maternal and infant outcomes. In a multinational study (IMPAACT 2010/VESTED) in 643 ART-naïve pregnant women randomized to initiate three different regimens (dolutegravir-TDF-emtricitabine, dolutegravir-tenofovir alafenamide-emtricitabine, or efavirenz-TDF-emtricitabine) during second trimester, a higher percentage of women receiving dolutegravir-based regimens achieved viral load suppression at delivery compared with women receiving the efavirenz-based regimen (98 versus 91 percent) . Neonatal mortality was also lower in the dolutegravir-based regimen groups compared with the efavirenz-based regimen group (1 and 2 versus 5 percent). In another multinational study (DolPHIN-2) in 268 ART-naïve pregnant women randomized to initiate dolutegravir-based or efavirenz-based therapy in the third trimester, more women in the dolutegravir-based regimen group achieved viral suppression at delivery compared with the efavirenz-based regimen group (74 versus 43 percent; risk ratio 1.64, 95% CI 1.31-2.06) . Although dolutegravir-based regimens were associated with higher likelihood of and faster viral suppression, the few vertical HIV transmissions that did occur occurred in the dolutegravir-based regimen groups. The transmissions were thought to have occurred in utero prior to the initiation of ART.
Although preliminary data from an observational study from Botswana suggested a potential association between maternal dolutegravir use at the time of conception and neural tube defects in the infants , final analysis showed the estimated increase in absolute risk was very low (0.2 percent) . Surveillance of the neural tube defect signal is ongoing and the WHO recommends dolutegravir-based therapy as the preferred first-line regimen for all individuals living with HIV, including females of reproductive potential living with HIV. (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Fetal safety'.)
Adverse effects/safety — The use of antiretroviral drugs during pregnancy has generally been found safe for both the mother with HIV as well as the infant. However, continued monitoring for end-organ toxicities in the mother and for toxicities and congenital anomalies in their infants is necessary to assure both short-term and long-term safety for both current and new agents as they become available. (See "Safety and dosing of antiretroviral medications in pregnancy".)
Drug resistance — At the population level, there are increasing rates of drug resistance mutations, particularly to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) and nucleoside reverse-transcriptase inhibitors in recently diagnosed individuals in resource-limited settings . In addition, multiclass resistance in both the mother and infant is possible if there is poor maternal adherence to ART; thus, continued counseling and adherence evaluation is a critical aspect of complete prevention of vertical transmission care (see 'Ongoing challenges' below). Unlike in resource-rich settings, such as the United States, where resistance testing is recommended prior to ART initiation in pregnant individuals newly diagnosed with HIV infection, resistance testing is not recommended to guide choice of ART in resource-limited settings, where a public health approach to ART is employed. The WHO recommends dolutegravir-based ART regimens for first-line treatment and specifically recommends avoidance of NNRTI-containing regimens in settings where NNRTI resistance rates are >10 percent .
Drug resistance is a growing global concern, including in individuals who are treatment naïve. In a study of approximately 600 women with HIV in Brazil, Argentina, and South Africa who presented late in pregnancy and thus did not receive antepartum ART, baseline drug resistance mutations were identified in 10 percent . Drug resistance was not associated with infection of the infant, but most infected infants of mothers with drug resistance were infected with virus that harbored the same mutations. Similarly, in a case-control study of 85 mother-infant pairs with vertical HIV transmission and 255 mother-infant pairs without transmission, maternal HIV drug resistance (predominantly to NNRTIs) was not associated with in utero or peripartum transmission of HIV but, along with maternal viral load, was associated with transmission during breastfeeding . (See "Use and impact of antiretroviral therapy for HIV infection in resource-limited settings", section on 'Drug resistance'.)
INFANT POSTNATAL PROPHYLAXIS
Prophylaxis for all exposed infants — In addition to maternal antiretroviral therapy (ART), the World Health Organization recommends that all newborn infants receive postnatal prophylaxis through four to six weeks of life to reduce the risk of vertical HIV transmission . Prophylaxis should start as soon as possible after birth, preferably within 6 to 12 hours.
Regimen selection — The recommended regimen depends on the infant’s risk of infection, as determined by the timing of maternal infection, maternal ART use, and the type of infant feeding (algorithm 1) .
High-risk infants — For nonbreastfed high-risk infants, the recommended prophylaxis regimen is daily nevirapine plus twice-daily zidovudine for the first six weeks of life (algorithm 1) . High-risk infants are those born to mothers with HIV who:
●have a viral load >1000 copies/mL within the four weeks prior to delivery
●received no ART or less than four weeks of ART by the time of delivery
●acquired HIV infection during pregnancy
●were diagnosed with HIV early postpartum
Recommendations for breastfeeding infants is discussed in detail elsewhere. (See "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Infant antiretroviral use'.)
Postnatal prophylaxis in infants reduces risk of vertical HIV transmission. In the ACTG 076 trial, performed in resource-rich countries, six weeks of zidovudine for the infant in combination with maternal zidovudine during pregnancy and intrapartum was associated with a vertical transmission rate of 8.3 percent compared with 25.5 percent in the placebo group .
The recommendation for a combination regimen for prophylaxis of high-risk infants is based on evidence demonstrating greater efficacy of two-drug compared with single-drug regimens in preventing vertical HIV transmission in cases when the mother is not on suppressive ART. In a trial conducted both in the United States and internationally, formula-fed infants of mothers who received no antepartum ART were randomly assigned to one of three arms: zidovudine for six weeks, zidovudine for six weeks plus three doses of nevirapine within the first eight days of life, and six weeks of zidovudine and lamivudine plus the protease inhibitor nelfinavir for two weeks. At six weeks, transmission rates were lower with the two- and three-drug combination therapy arms compared with the zidovudine alone group (2.2 and 2.4 versus 4.8 percent with nevirapine plus zidovudine, the nelfinavir-based three-drug regimen, and zidovudine alone, respectively) . However, while there was no difference in transmission between the two- and three-drug arms, there was significantly more hematologic toxicity in infants receiving the three-drug regimen. Observational studies of infants whose mothers received no intrapartum or antepartum ART have also demonstrated an associated reduction in HIV transmission with infant prophylaxis .
In contrast to resource-rich settings where three drug regimens are used for presumptive HIV therapy in high-risk infants, resource-limited settings continue to use a two-drug prophylaxis regimen approach. While the three-drug regimens are demonstrated to be safe, there is no evidence that they are more effective in preventing vertical HIV transmission than two-drug regimens in high-risk infants. It remains unknown whether newer antiretroviral agents (eg, dolutegravir, abacavir) can be substituted for zidovudine and nevirapine and whether a three-drug regimen confers any benefit over two drug-regimens when using these newer antiretroviral agents. The low rates of vertical transmission make comparative studies difficult to design, thus, it is unlikely that more data will be forthcoming.
Management of HIV-exposed infants who are identified in the postpartum period is discussed elsewhere. (See "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Infant antiretroviral use'.)
Low-risk infants — The risk of HIV infection in infants born to mothers who had achieved viral suppression on ART or who had been regularly taking ART for more than four weeks by the time of delivery is low. The recommended prophylaxis regimen is four weeks of daily nevirapine or twice-daily zidovudine for nonbreastfed infants  and six weeks for breastfed infants (algorithm 1). More detailed recommendations for breastfeeding infants is discussed elsewhere. (see "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Infant antiretroviral use')
The additive benefit of infant prophylaxis in infants born to mothers on effective contemporary ART with suppressed viral load is uncertain. In resource-rich countries, the duration of postexposure prophylaxis in infants born to mothers on ART with undetectable viral loads ranges from zero to six weeks of zidovudine alone. However, in resource-limited regions of the world, maternal viral load may not be known and using the public health approach of providing four to six weeks of infant postexposure prophylaxis likely benefits those infants whose mother is on ART but not virally suppressed.
Adverse effects/safety — In general, use of antiretrovirals is considered safe in infants. Because many antiretrovirals can cross the placenta, infants may be exposed in utero as well as through antiretrovirals prescribed to the infant or ingested by the infant through maternal breast milk. Zidovudine and nevirapine are generally safe and well tolerated in infants. Expected adverse events related to infant zidovudine use include transient anemia and neutropenia that typically resolves by 12 weeks of age; the incidence varies based on the underlying incidence in the population studied. The severe rash and potentially life-threatening hepatic injury associated with chronic nevirapine-based therapy in adults have not been reported in infants receiving a short course of nevirapine prophylaxis. (See "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Fetal and infant toxicity'.)
Drug resistance — Infants can acquire resistant HIV strains from their mothers or develop resistance by acquiring HIV via breastfeeding while on infant antiretroviral prophylaxis (eg, NNRTI-resistant HIV strain in an infant taking nevirapine for prophylaxis). In studies from resource-limited settings of infants born to women who were given efavirenz-based ART in a trial setting, multiclass resistance was detected in substantial proportions of infants who acquired HIV infection, particularly among those thought to be infected during the breastfeeding period [45,49,50]. These reports heighten concerns about emergence of multiclass antiretroviral resistance on a population basis if pregnant individuals with HIV acquire resistant virus at the time of infection, have treatment interruptions related to adherence difficulties, or loss to follow-up resulting in development of drug resistance.
MODE OF DELIVERY — The presence and status of HIV infection in the mother does not affect decisions on delivery mode in resource-limited settings. Although scheduled Cesarean sections are associated with reduced rates of perinatal transmission [51,52] and are recommended in individuals who have not achieved viral suppression (HIV viral load >1000 copies/mL) in resource-rich settings , this practice cannot be practically extended to resource-limited settings at this time.
PROGRESS TOWARD VERTICAL TRANSMISSION ELIMINATION AND ONGOING CHALLENGES
Progress toward elimination — Enormous progress has been made in the identification and treatment of pregnant individuals with HIV in resource limited settings. In 2020, an estimated 85 percent of pregnant individuals with HIV received antiretroviral therapy (ART) for their own health and to prevent vertical transmission of HIV to their infants . Vertical transmission rates have declined by more than half since 2010 . In particular, there has been striking success in prevention of vertical HIV transmission in a number of sub-Saharan African countries, with South Africa, Botswana, Eswatini, and Namibia reporting transmission rates of less than 4 percent . With the effective roll-out of ART to adult populations, increasingly more females are entering pregnancy already on ART; in 2020, the number was estimated to be more than 60 percent of those receiving ART. In addition, viral load monitoring and newer, more effective ART regimens are increasingly available in resource-limited settings.
Despite this remarkable progress, there were still an estimated 150,000 new pediatric HIV infections in 2020 . The Joint United Nations Programme on HIV/AIDS (UNAIDS) analyzes country-level data to produce estimates of the number of new pediatric infections and produces a stacked bar analysis by country and region to understand the causes of new infections among children. Contributing factors include new infections in young females, including pregnant and breastfeeding females, and persistent structural gaps in delivery of the vertical transmission prevention cascade services as well as issues of maternal adherence to ART. In eastern and southern Africa, for example, new infections among breastfeeding mothers contributed the highest proportion of new pediatric HIV infections. By comparison, in western and central Africa, low ART coverage among pregnant individuals resulted in the majority of new pediatric HIV infections . Additional gaps in the vertical transmission prevention cascade includes poor retention in care during pregnancy and postpartum and inadequate adherence to ART. (See 'Overview of care to prevent transmission' above.)
●Obstacles along the vertical HIV transmission prevention cascade − For prevention of vertical transmission services to be effective, interventions must achieve high uptake in all aspects of care, from antenatal services to linkage to HIV care postpartum. Real world challenges to the uptake of these services can occur at multiple points along the care cascade. (See 'Overview of care to prevent transmission' above.)
Obstacles for HIV care and treatment for pregnant people in resource-limited settings include:
•Low uptake of antenatal care − Pregnant individuals not accessing antenatal services at all or only coming for one antenatal visit
•Limited availability and scale-up of HIV and ART services in very resource-limited rural settings
•Deliveries occurring with private midwives, traditional birth assistants, or unassisted at home, instead of in health care facilities
•High rates of loss to follow-up attributed to individual, structural, and community factors
•Routine lack of commodities, including HIV test kits, antiretroviral agents, and laboratory reagents
•Inadequate health care worker staffing in maternal and child health (MCH) clinics and delivery settings
•Stigma associated with attending HIV clinics resulting in gaps in care and ART adherence
•Coronavirus disease 2019 (COVID-19)-related disruptions to health services
●Maternal HIV testing during pregnancy − Identification of HIV in pregnant individuals is critical to the control of vertical HIV transmission. Routine HIV testing is widely implemented at the first prenatal visit in most antenatal clinics. The “opt-out” approach to HIV testing (informing all pregnant individuals that they will be tested for HIV unless they specifically decline) has consistently resulted in >95 percent uptake of rapid same day HIV testing in a variety of international settings .
In addition, retesting individuals who initially test negative for HIV later in pregnancy, at delivery or early postpartum, and during lactation is an important intervention, as many infections occur during pregnancy. While retesting is widely recommended in high-prevalence settings, many programs have had difficulties establishing retesting procedures [55,56].
●ART coverage in pregnant individuals − Large-scale implementation of antiretroviral interventions that have been demonstrated to be effective in preventing vertical transmission in clinical trials has proved challenging in many resource-limited international settings. However, the widespread push for treatment of all individuals with HIV independent of clinical status and simplification of the approach to ART by using one recommended regimen across all populations has resulted in enormous advances in the treatment of pregnant individuals and reduction of vertical transmission rates . UNAIDS reported that coverage of antiretroviral programs for prevention of vertical transmission increased from 36 percent in 2009 to 85 percent in 2020 among their 21 priority countries .
●Poor maternal ART adherence and follow-up − Inadequate ART adherence and follow-up during pregnancy, particularly in the postpartum setting, are major obstacles for vertical transmission prevention programs [58-63]. In a systematic review and meta-analysis of studies evaluating adherence among pregnant and postpartum women with HIV in high- and low-resource settings, adherence was suboptimal for sustaining suppression of HIV viral load (ie, <90 percent adherence) throughout pregnancy, although better during the antepartum period than the postpartum period (76 versus 53 percent adherence, respectively) . In another study of over 30,000 pregnant Nigerian women with HIV, there was significant loss to follow-up at all points along the vertical HIV transmission prevention cascade and 16 percent of women were lost to follow-up after delivery . Conditional cash transfers and lay counseling are among the interventions shown to improve retention in care for women during pregnancy and postpartum [64-66].
Individuals whose pregnancies are unplanned may be at particular risk of ART nonadherence postpartum. In a prospective study following 459 postpartum South African women with HIV infection, loss of virologic suppression was increasingly reported over time, with at least one viral load >50 copies/mL detected in up to 43 percent by 36 to 60 months postpartum . Unplanned pregnancy was reported by 60 percent of women in this cohort and was associated with a higher likelihood of loss of virologic suppression than planned pregnancy.
Integration of HIV care into routine antenatal, postpartum, and pediatric health care services appears to improve follow-up rates. As an example, in a study from western Kenya of 363 infants exposed to HIV, those randomized to follow-up in a general MCH service with integrated HIV care had better follow-up rates compared with infants who had to follow-up in a specialized HIV comprehensive care clinic .
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: HIV treatment in pregnant women".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: HIV and pregnancy (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Burden of disease − Greater than 90 percent of all new pediatric HIV cases result from vertical transmission. Sub-Saharan Africa carries the greatest burden of the epidemic. (See 'Burden of disease' above.)
●Risk of vertical HIV transmission – Without antiretroviral preventive interventions, the risk of vertical HIV transmission has varied between 15 and 45 percent. Maternal viral load and incident infection during pregnancy are the two most important factors affecting risk of transmission. (See 'Risk of vertical HIV transmission' above.)
●Timing of vertical HIV transmission − Vertical transmission of HIV can occur during pregnancy (in utero), at labor/delivery (perinatal), or postdelivery (postnatal) through breastfeeding. A majority of in utero transmission is thought to occur during the third trimester. (See 'Timing of vertical HIV transmission' above.)
●Overview of care to prevent transmission − The use of antiretroviral agents by pregnant individuals and their children is the most important intervention for prevention of vertical transmission. Successful prevention programs must also include other measures for optimal identification and long-term management of pregnant individuals with HIV. These include rapid HIV testing, monitoring and support for antiretroviral adherence and toxicity, counseling on infant feeding, effective family planning and reproductive health services, and linkage to long-term HIV care. (See 'Overview of care to prevent transmission' above.)
●Maternal antiretroviral therapy – The World Health Organization (WHO) recommends lifelong antiretroviral therapy (ART) for all pregnant individuals with HIV to reduce the risk of transmission to their infants and for their own clinical benefit. The WHO preferred first-line ART regimen is dolutegravir, tenofovir disoproxil fumarate, and lamivudine (or emtricitabine). Individuals already taking effective ART prior to pregnancy should generally continue the same regimen throughout pregnancy. (See 'Maternal antiretroviral therapy' above.)
●Infant postnatal prophylaxis – In addition to maternal ART, the WHO recommends that all newborn infants receive postnatal prophylaxis through four to six weeks of life to reduce the risk of vertical HIV transmission. Prophylaxis should start as soon as possible after birth, preferably within 6 to 12 hours. The recommended regimen and duration depends on the infant’s risk of infection, as determined by the timing of maternal infection, maternal ART use, and the type of infant feeding (table 1 and algorithm 1).
●Mode of delivery − The presence and status of HIV infection in the mother does not affect decisions on delivery mode in resource-limited settings. (See 'Mode of delivery' above.)
●Adverse effects and safety of antiretroviral agents − The use of ART during pregnancy has generally been found safe and the benefits for preventing transmission of a fatal illness outweigh the potential adverse reactions that may occur. (See 'Maternal antiretroviral therapy' above and 'Infant postnatal prophylaxis' above and "Safety and dosing of antiretroviral medications in pregnancy".)
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