Epidemiology and Prevention of HIV Infection in Infants, Children, and Adolescents

Epidemiology

The epidemiology of HIV infection varies dramatically between resource-poor and resource-rich settings around the world. Estimates of the extent of the HIV epidemic, globally and in the US, are updated regularly by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and by the US Centers for Disease Control and Prevention (CDC), respectively. Of the estimated 37.7 million people living with HIV infection in 2020 (most [20.6 million] residing in eastern and southern Africa), 1.7 million were children younger than 15 years. Of the estimated 1.5 million new infections in 2020, 150,000 were among children under the age of 15 years. In 2019, the number of persons living with a diagnosis of HIV infection in the US and dependent areas with confidential name-based HIV infection reporting included 1693 children (<13 years of age).

Both in the US and globally, infants and children primarily acquire HIV infection through mother-to-child transmission ( Table 109.1 ). For example, of the 1693 children reported to be living with HIV infection in the US in 2019, 1371 (81%) of them were classified as having acquired infection through mother-to-child transmission. There has been a dramatic decrease in the rate of mother-to-child transmission of HIV and in the number of pediatric HIV infections in the US; while the estimated number of cases of mother-to-child transmission of HIV in the US in 1991 was 1650, by 2005 such cases had decreased to an estimated 215–370. More recently, the number of cases of mother-to-child transmission decreased from 108 in 2010 to 48 in 2016. Mother-to-child transmission of HIV can occur during pregnancy, around delivery, and postnatally through breastfeeding. Most transmission occurs during the intrapartum period in both breastfeeding and non-breastfeeding populations. Rates of mother-to-child transmission of HIV were calculated in studies conducted in various countries before the development and implementation of interventions to decrease transmission. Usually a transmission rate in the range of 25%–30% was reported; higher transmission rates were observed in resource-poor settings (13%−42%) compared with rates in resource-rich settings (14%−25%), in part attributed to the greater proportion of breastfeeding women in resource-poor settings. Various risk factors for mother-to-child transmission of HIV have been identified or are under investigation and can be categorized as follows: (1) the amount of virus to which the child is exposed (e.g., maternal viral load, expressed as copies/mL of HIV RNA), (2) the duration of such exposure (e.g., the duration of ruptured membranes or breastfeeding, vaginal versus cesarean delivery before labor and before ruptured membranes ^, ), and (3) other factors, including those facilitating the transfer of virus from mother to child (e.g., mixed breastfeeding, ^, maternal breast pathology, ^, and infant oral candidiasis ^, ). In addition to these risk factors, characteristics of the virus and the child’s susceptibility to infection are important.

Many cases of HIV infection in young adults represent acquired during adolescence but not recognized until several years later. In 2019, the number of persons living with a diagnosis of HIV infection in the US and dependent areas with confidential name-based HIV infection reporting included 4858 adolescents (13–19 years of age) and 25,924 young adults (20–24 years of age). Among the estimated 800,035 male adults and adolescents living with HIV infection in 2019, 587,555 (73%) of these infections were acquired through male-to-male sexual contact, 67,603 (8%) were due to injection drug use, 56,719 (7%) were due to male-to-male sexual contact and injection drug use, and 80,351 (10%) were due to heterosexual contact ( Table 109.1 ). In contrast, among the estimated 243,249 female adults and adolescents living with HIV infection in 2019, 187,127 (77%) were acquired through heterosexual contact and 48,660 (20%) from injection drug use ( Table 109.1 ).

Aside from mother-to-child transmission, sexual contact (vaginal, anal, or orogenital), and transmission related to intravenous drug use, other means of acquisition of HIV infection include transfusion of contaminated blood or blood products in settings in which routine and effective screening of blood is not available, percutaneous blood exposure (from contaminated needles or other sharp instruments), and mucous membrane exposure to contaminated blood or other body fluids ( Table 109.1 ). The first case of pediatric HIV infection in the US was an infant who acquired the infection through a transfusion of contaminated blood. Thousands of patients with hemophilia and other recipients of contaminated blood and blood products acquired HIV infection before screening of blood and blood products for HIV. Now, in the US and many other countries, blood, blood components, and clotting factors undergo effective screening procedures. As a result, transmission of HIV through transfusion of blood or blood products in the US has decreased substantially. The risk for transmission of HIV through blood transfusions in the US has been estimated at 1 per 1,467,000.8. In addition to intravenous drug use, other exposure to contaminated needles (e.g., with tattooing) can result in HIV transmission. Possible transmission of HIV through receipt of food that has been prechewed by an HIV-infected caregiver with bleeding gums or open sores in the mouth has been reported. There have been rare cases of household transmission of HIV between siblings, but in these cases, there were opportunities for skin or mucous membrane exposure to HIV-infected blood. Thus, all caregivers of HIV-infected children should receive education regarding universal precautions. Cases of HIV transmission to children through sexual abuse have been reported. Transmission of HIV has not been described as a result of routine outpatient or inpatient care or in schools or childcare settings in the US. ^,

Clinical Manifestations and Progression

Infection with HIV can result in a myriad of clinical manifestations. AIDS or AIDS, refers to the most advanced disease stage of HIV infection. AIDS is defined by the development of life-threatening manifestations, including opportunistic infections and neoplasms, due to progressive immunosuppression induced by HIV infection.

The natural history of HIV infection in infants who acquired the infection through mother-to-child transmission differs from that in adults. Plasma viral loads among untreated, infected infants increase rapidly after birth, peaking at 1–2 months of age (median values of 318,000 and 256,000 copies/mL, respectively). Untreated, viral loads decline slowly during the first 2 years of life, reaching values observed in HIV-infected adults only at approximately 5 years of age. Studies of HIV-infected infants who acquired infection through mother-to-child transmission that were published in the late 1990s, at a time when pediatric antiretroviral treatment was limited, described rapid progression of disease. Early onset of clinical manifestations of HIV infection (lymphadenopathy, hepatomegaly, splenomegaly at 3 months of age or earlier) and positive HIV diagnostic testing within the first week of life were associated with more rapid disease progression. In subsequent studies of HIV-infected children in Africa, more than one-third of untreated, HIV-infected infants died by 12 months of age, and approximately one-half died by 24 months of age. After the introduction of more effective antiretroviral regimens, the morbidity and mortality associated with HIV infection among infants, children, adolescents, and adults has decreased substantially. Opportunistic and other infections were uncommon among HIV-infected children in 2000–2004, and infection rates were lower than those reported in earlier years. Similarly, the incidence of certain noninfectious conditions (encephalopathy, pancreatitis, cardiac disorders) decreased between 2001 and 2006 among HIV-infected children and adolescents. In a randomized clinical trial conducted in South Africa, infants with early time-limited antiretroviral therapy had better clinical and immunologic outcomes than infants with deferred therapy. Also, infants with early antiretroviral therapy did not have excess disease progression during subsequent treatment interruption. Based on these data and the high risk for rapid progression of HIV infection in infants, urgent antiretroviral therapy for all HIV-infected infants is recommended, regardless of clinical, immunologic (CD4 ⁺ lymphocyte percentage), or viral load status.

There is substantial variation in HIV disease progression among adolescents and adults; some individuals progress to AIDS in <5 years while some untreated individuals (so-called long-term non-progressors) do not deteriorate clinically or immunologically for many years. Current guidelines for initiation of antiretroviral therapy in HIV-infected adolescents and adults recommend the initiation of antiretroviral therapy in all HIV-infected individuals, regardless of CD4 ⁺ lymphocyte count, to decrease morbidity and mortality related to HIV infection. Antiretroviral therapy should be initiated as soon as possible after diagnosis of HIV infection, although in certain circumstances (i.e., related to clinical and/or psychosocial factors), therapy may be deferred.