Thinking About HIV Infection

Case Study 1

A 20-year-old woman, who is a recent emigrant from Ethiopia, brings in her 4-month-old infant for a health supervision visit. The baby has had no immunizations, and his mother reports having had no prenatal care. She is breastfeeding exclusively. The infant's 25-year-old father recently died after being very sick for 2 years. The mother states that he had “bad lungs.” What are your next steps?

Case Study 2

A 17-year-old honor student comes to your office with a maculopapular rash on his face, trunk, palms, and soles. He also complains of a sore throat and fever and states that he recently returned from visiting his grandmother in Georgia. During his visit, he went hunting with his uncles and his grandmother's dog. During the interview, which involves asking routine psychosocial questions in a nonthreatening manner (Table 1) to elicit sensitive information, he states that he has been sexually active with women for 2 years and with men for 6 months. He does not use condoms with either. He denies any contacts with sick persons or substance abuse, including injection drug use (IDU). What are your next steps?

The Tests

Several laboratory tests are approved for screening and diagnosing HIV infection (Table 3). The pediatrician must select the correct test based on the patient's age and the clinical indication (Table 4). Most commercially available tests detect HIV antibody. For patients older than age 18 months, the confirmed presence of antibody to HIV is diagnostic of HIV infection. Standard HIV antibody testing is performed on a blood specimen in two steps: screening enzyme-linked immunoassay (EIA) is performed and if reactive, a confirmatory test such as Western blot is performed. Both steps must be positive for the overall test result to be reported as positive.

Newer rapid tests also detect antibody; they are performed on blood or saliva and allow the clinician to provide a result to a patient in approximately 20 minutes. Positive screening results must be confirmed by standard antibody testing. Specific HIV viral detection using DNA or RNA polymerase chain reaction (PCR) is necessary in two clinical situations when antibody testing is nondiagnostic: in infants of HIV-infected mothers and in patients of any age who are suspected of having acute or early HIV infection. All infants born to HIV-positive mothers test positive for HIV antibody due to the transfer of maternal immunoglobulin across the placenta; HIV DNA or RNA PCR identifies those who have true HIV infection. Older children and adolescents who have symptoms of acute retroviral syndrome may not yet have detectable HIV antibody; HIV RNA PCR is a sensitive test for early HIV infection. A definitive diagnosis of HIV infection requires that two different specimens test positive (eg, in children older than 18 months, two antibody tests or one antibody + one RNA) using appropriate techniques based on the age of the patient and the clinical indication.

Counseling and Consent

National HIV testing guidelines recommend counseling and testing as a routine part of regular medical care in addition to continued efforts to reach out to individuals at higher risk. The goal is to identify all HIV-positive individuals, engage them in HIV care for their own health, and reduce the transmission of HIV to others. Clear, understandable information about the benefits of HIV testing should be provided in a manner that protects patient privacy and provides emotional support as needed. Key messages include that: 1) HIV infection is a treatable condition, 2) HIV infection is a serious health condition, 3) early detection of HIV infection permits early treatment to prevent disease progression and maintain health, and 4) people who have HIV infection can prevent its transmission to others. The “opt-out” counseling approach informs patients that HIV testing will be performed as part of their routine care unless they decline, reducing barriers associated with mandatory prevention counseling and written consent. Adolescents in the United States can seek confidential testing and treatment for HIV independently, although family support is encouraged.

Parents or guardians seek care on behalf of infants and children. Children should be included in developmentally appropriate discussions about care. Anticipating the need for HIV disclosure to the child is an important component of the pediatric counseling process. Helping adult caregivers understand the importance of sharing simple and truthful information provides a strong foundation for later disclosure. The indication for diagnostic testing may help frame the conversation (eg, mother is HIV-positive, sibling is HIV-positive, child has worrisome clinical findings). Counseling messages include:

All ages: Inform child that a blood test will be performed, give simple details of the procedure, help choose a coping strategy, and offer comfort.

4 to 6 years of age: “I am worried that you keep getting sick. I need to do a blood test to help me figure out why.”

7 to 10 years of age: “I am worried that you keep getting sick. I wonder if your immune system, the part of your body that fights off infections, isn't working the way it should. I want to do blood tests to help me figure this out.”

11 to 13 years of age: “I am worried that you keep getting sick. I wonder if your immune system, the part of your body that fights off infections, isn't working the way it should. I want to do blood tests to help me figure this out. One of the tests looks for HIV. Have you ever heard of that?”

The most important guideline is never lie. Partial truthfulness can be supplemented at later visits or at older ages. Deliberate misinformation, even under the guise of protecting the child, leads to loss of trust and is very difficult to undo.

Screening Pregnant Women

Universal HIV counseling and voluntary HIV testing using an opt-out approach is the recommended standard of care for all pregnant women in the United States. This practice provides the opportunity for HIV-positive women to access HIV care for their own health and to prevent HIV transmission to their babies. The opt-out approach informs all pregnant women receiving care that an HIV test will be performed unless she opposes testing. Initial testing is performed early in pregnancy. Repeat testing is recommended in the third trimester (before 36 weeks’ gestation) for women who live in high HIV prevalence areas or for women who have specific high-risk factors (exchange sex for money or drugs, IDU, sexual partner who engages in IDU, new diagnosis of sexually transmitted infection during pregnancy).

For women who have not received prenatal care, intrapartum testing should be offered by using rapid test kits or expedited EIA. Mothers who decline screening at any of these opportunities should be offered testing again at every opportunity, including rapid antibody testing in the immediate postpartum period. Practitioners also can offer rapid antibody testing of newborns as an indicator of HIV exposure when the mother's status cannot be determined. In most cases, maternal consent is needed for testing newborns, but some states allow testing of high-risk newborns without consent.

Testing HIV-Exposed Infants

Infants born to HIV-positive mothers should undergo specific diagnostic testing; HIV DNA or RNA PCR should be used as part of their health maintenance care. Testing is recommended at age 14 to 21 days, at 1 to 2 months, and again at 4 to 6 months. Due to the low sensitivity of tests in the first 48 hours after birth, testing is optional at birth. If performed, blood samples from the umbilical cord should not be used because of possible contamination with maternal blood. In nonbreastfed infants, the sensitivity of HIV DNA PCR increases to 93% by 14 days of age. By 28 days, the sensitivity increases to 96% and the specificity is 99%. Sensitivity and specificity of the HIV RNA assay are similar. Any positive test requires repeat confirmatory testing as soon as possible. Some practitioners use HIV DNA PCR for initial testing and HIV RNA assay for confirmatory testing.

HIV infection is reasonably excluded when results of two virologic tests are negative, the first at 14 days or older and the second at 1 month of age or older. Definitive exclusion requires negative results for two virologic tests, the first at age 1 month or older and the second at 4 months of age or older. In older infants for whom early testing was not performed, an alternate strategy is to confirm the absence of HIV antibody. If infection already has been excluded definitively, HIV antibody testing between 12 and 18 months of age to confirm the loss of maternal antibody is optional.

Breastfeeding causes continued HIV exposure and is not recommended in the United States where safe replacement (formula) feeding can be provided. Testing should continue throughout the period of breastfeeding and for 6 months after cessation when an infant is breastfed.

Testing Children and Adolescents

HIV antibody tests are used for screening and diagnosis in children older than age 18 months. All children of HIV-positive mothers should be screened for HIV infection regardless of age or healthy appearance. Children or adolescents who present with clinical conditions suggestive of HIV infection should undergo HIV testing as part of the diagnostic evaluation, regardless of risk history.

All adolescents should be offered HIV testing as part of routine health care. Annual testing is recommended for those at high risk of acquiring HIV infection. Rapid tests offer the advantage of providing test results at the same visit. HIV-negative individuals can be reassured and counseled to avoid future HIV exposure. HIV-positive individuals can be engaged immediately into care and support.

If a practitioner suspects acute infection or acute retroviral syndrome, he or she should order HIV antibody and nucleic acid testing (HIV RNA) to look for evidence of infection. A positive nucleic acid test result in the presence of a negative or indeterminate antibody test result is consistent with acute HIV infection. Antibody testing is recommended 10 to 12 weeks later to confirm seroconversion.

Evaluation and Staging of the HIV-Positive Patient

Patients who have positive HIV test results should be referred to an HIV specialist for comprehensive evaluation (Table 5) so the clinical and immunologic stage of disease can be assessed and treatment recommended. Initial evaluation of an HIV-infected pediatric patient should include the mother's medical history, child's medical history, family history, and social history. A comprehensive physical examination should be performed and documented, including a developmental evaluation. Assessment of HIV-infected adolescent patients (generally, 11 years of age and older), as for all adolescents, should include a sexual history, substance use history, and sexual maturity staging.

Initial laboratory testing in an HIV-positive patient should include CD4 percentage and absolute cell counts, plasma HIV RNA concentration (viral load), HIV genotype to assess for baseline resistance mutations, complete blood count with differential count, serum chemistries with liver and renal function tests, a lipid profile, and urinalysis. For children younger than 5 years of age, CD4 percentage is the preferred test for monitoring immune status because the absolute CD4 cell count (number of CD4 cells/mm³) in this age group varies with age-related changes in absolute lymphocyte count. Screening for hepatitis B and C infection as well as for tuberculosis is recommended for all HIV-infected patients. In addition, sexually active adolescents should be screened for Chlamydia infection, gonorrhea, syphilis, and human papillomavirus infections. In contrast to the guidelines for cervical cancer screening in healthy women, cervical Papanicolaou smears are indicated routinely in all sexually active, HIV-infected adolescent girls, with colposcopy recommended for evaluation of abnormal results. Similarly, most experts perform anal Pap smears in HIV-infected adolescent men who have sex with men and HIV-infected sexually active women; anoscopy is recommended for evaluation of abnormal results.

HIV infection is a multisystem disease; clinical manifestations range from asymptomatic to complications affecting virtually every organ system (Table 6). The Centers for Disease Control and Prevention classification system designates clinical categories based on the patient's medical history and immunologic function categories based on CD4 percentage (Table 7). This information permits an estimated risk for future morbidity and mortality and provides a rationale for instituting specific opportunistic infection prophylaxis and initiating or deferring antiretroviral therapy.

Antiretroviral Therapy

The goal of anti-HIV therapy is to maximize the quality and longevity of life through:

• Complete suppression of viral replication (goal of nondetectable viral load)

• Preservation or restoration of immunologic function (goal of normal CD4 percentage or count)

• Prevention of or improvement in clinical disease (goal of asymptomatic state)

National treatment guidelines for HIV-infected children and adolescents are updated routinely and are available on the Internet (http://www.aidsinfo.nih.gov/Guidelines/). Current recommendations are summarized in the text and in Table 8. The pediatric treatment guidelines updated in 2008 recommend antiretroviral treatment for all infected infants (<12 months old); simplifies treatment initiation recommendations into three age categories (<12 months old, 1 to 4 years old, and ≥5 years old) instead of four; places greater emphasis on simplified, age-based CD4 thresholds for treatment initiation than on viral load; and is consistent with adult guidelines for initiation of antiretroviral treatment in children 5 years of age and older. Clinical and immune statuses are key predictors of morbidity and mortality and form the basis for these recommendations. Viral load is more useful for monitoring adherence and effectiveness of therapy than as an indicator of when to initiate antiretroviral therapy.

Treatment is recommended for: AIDS or severe symptoms, CD4 percentage of less than 25% (1 to 4 years) or absolute CD4 count of less than 350 cells/mm³ (5 years and older) regardless of symptoms, all infected infants younger than 12 months of age, and all pregnant adolescents.

Treatment is considered for: patients whose HIV RNA is more than 100,000 copies/mL and who have mild or absent symptoms and adequate CD4 cells (CD4 percentage of more than 25% [1 to 4 years] or absolute CD4 count of more than 350 cells/mm³ [5 years and older]).

Treatment can be deferred for: mild or absent symptoms and adequate CD4 values (CD4 percentage of more than 25% [1 to 4 years] or absolute CD4 count of less than 350 cells/mm³ [5 years and older]) and RNA of less than 100,000 copies/mL.

Antiretroviral therapy should be planned and monitored in collaboration with an HIV specialist. Strong evidence supports the use of triple-drug combination antiretroviral therapy to maximize virologic response and minimize the emergence of viral resistance. Initial therapy consists of three drugs from two categories: one non-nucleoside reverse transcriptase inhibitor (NNRTI) OR protease inhibitor (PI) PLUS two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs).

Important issues to consider when selecting specific drugs include:

• Age, weight, sexual maturity stage of patient

• Baseline HIV resistance pattern

• Likelihood of developing resistance to selected drugs if patient has difficulty adhering to the regimen (low versus high barrier to resistance)

• Likelihood of becoming pregnant while taking selected drugs (eg, efavirenz)

• Ease of administration (formulation, schedule, food restrictions)

Planning treatment collaboratively with the patient and family strengthens the therapeutic relationship and promotes successful adherence and HIV control. Enlisting adult support in the home is beneficial regardless of the patient's age. Frequent clinical follow-up with viral load testing allows the clinician to identify problems early and help patients and families find successful solutions. Patients in whom the virus shows no drug resistance and in whom therapy is initiated with currently available medicines should achieve a nondetectable viral load within 3 to 6 months. Failure to achieve this goal strongly suggests suboptimal adherence to the recommended regimen rather than viral resistance.

Once HIV infection is controlled on a stable regimen, most patients are seen every 3 to 4 months for routine monitoring of viral load, CD4 cell response, and clinical status, including evaluation for potential medication adverse effects or toxicities. Patients who experience treatment failure have additional treatment options, including new drugs in existing classes (PIs, NNRTIs, NRTIs) as well as new drug classes such as entry inhibitors (fusion inhibitors and CCR5 antagonists) and integrase inhibitors.

Preventing Opportunistic Infections

The profound immunodeficiency caused by uncontrolled HIV infection allows serious and life-threatening infections to occur in children and adolescents. Evidence supports the primary prevention of common opportunistic infections (OIs) based on age and CD4 guidelines. Full recommendations are available at http://aidsinfo.nih.gov.

Pneumocystis jiroveci pneumonia (PCP) is the most common OI. Cotrimoxazole is recommended for all HIV-exposed infants until HIV infection is reasonably excluded, for all HIV-infected infants until age 12 months, and for HIV-infected children and adolescents older than 1 year of age whose CD4 values fall into the severe immune suppression category (CD4 percentage <15% or CD4 count <200 cells/mm³).

Primary prevention of Mycobacterium avium complex by using azithromycin or clarithromycin is recommended at lower CD4 values (≥6 years old with CD4 count of <50 cells/mm³; ages 2 to 5 years with CD4 count of <75 cells/mm³; 1 to 2 years with CD4 count of <500 cells/mm³; <1 year old with CD4 count of <750 cells/mm³).

Toxoplasmosis is less common in children than in adults, but its prevention with daily cotrimoxazole is recommended in HIV-infected children and adolescents who are Toxoplasma immunoglobulin G-seropositive and have severe immunosuppression (CD4 percentage <15% for children <6 years old; CD4 count <100 cells/mm³ for children ≥6 years old).

Immunizations

The 2009 immunization schedule for HIV-exposed infants and for HIV-infected infants, children, and adolescents is the same as for their healthy peers, with only a few exceptions. Patients who have severely symptomatic illness or CD4 percentages of less than 15% or CD4 counts of less than 200 cells/mm³ should not receive measles-mumps-rubella (MMR) or varicella vaccines due to the risk of opportunistic disease from the live attenuated virus strains in the vaccines. HIV-infected children who have higher CD4 counts should receive MMR and varicella separately, not as the combined MMR-V. The higher titer of varicella in MMR-V has not been tested for safety in HIV-infected children. Annual influenza immunization is recommended for all children older than age 6 months, but only the killed, injectable formulations of the influenza vaccine are recommended for HIV-infected children and adolescents.

HIV-infected children and adolescents need certain additional vaccines and doses. Pneumococcal polysaccharide vaccine is recommended in addition to the regular pneumococcal conjugate vaccine series. Specific and comprehensive recommendations for immunizations in HIV-infected children, adolescents, and adults are available at http://aidsinfo.nih.gov/.

Primary and Secondary Prevention of HIV Infection

Health education messages to avoid HIV infection and to prevent its spread to others should be routine in every pediatric and adolescent practice. It is important for clinicians to be prepared to offer prevention counseling, including abstinence and safe sex as best options for preventing HIV transmission. Clinicians should be able to teach all adolescents about correct use of male latex condoms and emphasize that consistent use is essential for prevention. Screening all patients ages 13 years and older for HIV infection identifies asymptomatic patients unaware of their HIV infection status, providing them the opportunity to enroll in HIV-specific care for their own benefit and to reduce the risk of transmitting HIV to others. HIV-negative adolescents who engage in behaviors through which HIV can be transmitted should be tested at least annually.

Coping With the Diagnosis and Prognosis

Learning of a new diagnosis of HIV infection for oneself or one's child is emotionally devastating for most people. While providing a listening ear and emotional support, clinicians also can offer hope and reassurance about the availability of effective treatment that can result in improved quality of life and survival for people living with HIV infection in the United States. Referral to the HIV specialist allows prompt access to specific medical care and psychosocial supports.

Disclosure of HIV Infection Status

HIV infection remains a stigmatizing diagnosis. Ignorance, misinformation, and fear in families and communities cause people living with HIV infection to keep their status a secret. However, this practice has negative consequences, such as isolating the HIV-positive individual from social support and risking additional spread of HIV to sexual partners. Planned disclosure to family members and friends can increase practical and emotional support for the HIV-positive person. Sexual partners can make informed decisions about how to protect themselves from exposure to HIV.

In contrast to adolescents and adults, disclosure of HIV status to children should be undertaken over time, providing sequential pieces of practical health information that match the developmental capacity of the child. This process builds a strong foundation for children to participate meaningfully in their HIV care.

Adherence to Care and Treatment

Most people do not adhere to the treatment recommendations of their health-care practitioners all of the time. Adolescence is a particularly vulnerable age for nonadherence in those who have chronic health conditions such as HIV infection. Poor adherence leads to poor health outcomes in many diseases such as asthma and diabetes. However, HIV treatment is unique in its requirement for 90% to 100% adherence to drug regimens to avoid the development of viral resistance and the loss of future efficacy of anti-HIV drugs. The need for intensive education and support for children and adolescents living with HIV infection cannot be overstated.

School and Sports Participation

Children and adolescents who have HIV infection can participate fully in the educational and extracurricular activities in school. There is no obligation to notify school personnel of a student's HIV infection status. Any sport may be played if the student's health status allows. For all athletes, regardless of HIV infection status, skin lesions should be covered properly, and athletic personnel should use standard precautions when handling blood or body fluids that have visible blood. Certain high-contact sports (such as wrestling and boxing) may create a situation that favors viral transmission (likely bleeding plus skin breaks). Some experts advise athletes who have a detectable viral load to avoid such high-contact sports.

Transition to Adult Health Care

Children born with HIV infection in the United States during the 1980s are now young adults. They continue to be the pioneers who challenge our assumptions and identify unmet needs for care and support services. No one anticipated the current need to develop and implement programs to transition youth successfully to adult HIV health-care clinicians. Practical concerns such as transmitting a complete and coherent medical record and psychological concerns such as the loss of long-term supportive relationships must be addressed.

Advance Care Planning and Palliative Care

Advance care planning is recommended for all who live with chronic and life-threatening conditions. HIV-infected parents should plan for the care of their dependent children. HIV-infected adolescents and young adults should designate a person they trust to make health-care decisions for them if they should become unable to speak for themselves due to illness or injury. One approach is to normalize this decision as part of routine health care when reaching adulthood. This practice is particularly important for youth who have no clearly identified next of kin, such as those who are orphaned and have experienced sequential foster homes.

There continue to be patients who experience distressing medical complications of HIV infection that, if not reversed, lead to death. Integrating palliative care with HIV-specific care reduces distress by managing specific physical and emotional symptoms, encouraging clear communication, and promoting effective decision-making. This approach provides the best opportunity to improve a patient's quality of life regardless of how long the patient survives.