Porth's Essentials of Pathophysiology, 4e

371

Disorders of the Immune Response

C h a p t e r 1 6

by the presence of maternal anti-HIV IgG antibody, which crosses the placenta to the fetus. 82 Consequently, infants born to HIV-infected women can be HIV anti- body positive by ELISA up until 18 months of age even though they are not infected with HIV. Polymerase chain reaction testing for HIV DNA is used most often to diagnose HIV infection in infants younger than 18 months of age. Two positive PCR tests are needed for diagnosis. Children born to mothers with HIV infection are considered uninfected if they become HIV antibody negative after 18 months of age, have no other labora- tory evidence of HIV infection, and have not met the case definition criteria for AIDS in children. The landmark Pediatric AIDS Clinical Trials Group (PACTG) 076 study reported that perinatal transmis- sion could be lowered by two-thirds, from 26% to 8%, by administering zidovudine to the mother during preg- nancy and labor and delivery and to the infant when it is born. 83 The U.S. Public Health Service therefore recommends that HIV counseling and testing should be offered to all pregnant women. 84 The recommen- dations also stress that women who test positive for HIV antibodies should be informed of the perinatal prevention benefits of zidovudine therapy and offered HAART, which often includes zidovudine. This is done because it has been found that women receiving antiretroviral therapy who also have a viral load less than 1000 copies/mL have very low rates of perinatal transmission. Efavirenz, a non-nucleoside reverse tran- scriptase inhibitor, has the potential for causing neural tube defects within the first 6 weeks of pregnancy. HIV- infected women of child-bearing age should be tested for pregnancy and counseled regarding the potential adverse effects prior to initiating HAART with efavi- renz. If a woman is taking an efavirenz-based regimen and pregnancy is determined after 6 weeks, then she may continue the regimen as long as virologic suppres- sion is maintained and the pregnancy is monitored. 79 Benefits of voluntary testing for mothers and newborns include reduced morbidity because of intensive treat- ment and supportive health care, the opportunity for early antiretroviral therapy for mother and child, and information regarding the risk of transmission from breast milk. Clinical Manifestations. Children may have a differ- ent clinical presentation of HIV infection than adults. 82 Failure to thrive, CNS abnormalities, and developmen- tal delays are the most prominent primary manifesta- tions of HIV infection in children. Children born with HIV infection usually weigh less and are shorter than noninfected infants. A major cause of early mortality for HIV-infected children is P. jiroveci pneumonia, which occurs early in children, with the peak age of onset at 3 to 6 months. For this reason, prophylaxis with tri- methoprim-sulfamethoxazole should be started begin- ning at 4 to 6 weeks for all infants born to HIV-infected mothers, regardless of their CD4 + cell count or infection status. 85

Two new classes of antiretroviral therapy are the entry inhibitors and integrase inhibitors. The entry inhibitors prevent HIV from entering or fusing with the CD4 + cell, thus blocking the virus from inserting its genetic information into the CD4 + T cell. The integrase inhibi- tors block the integration step of the viral cycle, thus preventing the HIV genome from integrating into the host’s genome. Because different drugs act at different stages of the replication cycle, optimal treatment includes a combina- tion of at least three antiretroviral drugs, referred to as highly active antiretroviral therapy (HAART). The goal of HAART is a sustained suppression of HIV replica- tion, resulting in an undetectable viral load and increas- ing CD4 + cell count. In general, antiviral therapies are prescribed to slow the progression of AIDS and improve the overall quality of life and survival time of persons with HIV infection. Preventive and therapeutic vaccines for HIV are also being investigated. 80 The preventive vaccine would be given to someone who is HIV negative, with the goal of preventing infection if exposed to HIV. The therapeutic vaccine would be used in people who are already infected with HIV as a way to control HIV replication. In trials to date, these vaccines have not proven beneficial. A new preventive strategy has been approved by the FDA in the United States. PrEP—pre-exposure prophy- laxis—involves consistently taking antiretroviral medi- cation that may interrupt infection if exposed to HIV in high-risk settings. It is not 100% effective at prevent- ing HIV infection; routine counseling on reducing risky behaviors and routine evaluations for sexually transmit- ted infections are still paramount. Individuals taking PrEP also need to be routinely monitored for efficacy and side effects of the medication. Transmission from mother to infant is the most com- mon way that children become infected with HIV. Human immunodeficiency virus may be transmitted from infected women to their offspring in utero, dur- ing labor and delivery, or through breast-feeding. 81 Most transmissions from mother to child occur during childbirth when the mother’s infected blood in the birth canal infects the baby. Breast-feeding, particularly in poor countries, can account for one third to one half of all mother-to-child transmission. Screening programs for pregnant women and antiretroviral prophylaxis are available for preventing mother-to-child transmission in HIV-positive women. Epidemiologic estimates suggest that coverage for antiviral prophylaxis to HIV-positive women for prevention of mother-to-child transmis- sion in low- to middle-income countries increased from 9% in 2004 to 33% in 2007 to 57% in 2011. 44,47 Diagnosis and Treatment. Diagnosis of HIV infection in children born to HIV-infected mothers is complicated HIV Infection in Pregnancy and in Infants and Children