University of California, San Francisco Logo

University of California, San Francisco | About UCSF | Search UCSF | UCSF Medical Center

transparent gif
transparent gif
Home > Topics > Pediatric Summaries > Recurrent Illness
transparent gif

Pediatric Case Discussion Summary: 2-Year-Old HIV-Positive Child with Recurrent Illness and Undetectable Viral Load

Transparent Image
transparent gif
Introduction
transparent gif
The Case
transparent gif
Question 1: What treatment should be initiated?
transparent gif
Question 2: What further tests should be performed?
transparent gif
Question 3: If both parents are HIV negative, how could this child have acquired HIV?
transparent gif
Expert Opinions
transparent gif
Follow-Up
transparent gif
Conclusion: Women, Children, and HIV Analysis
transparent gif
transparent gif
transparent gif

Introduction

transparent gif

The Paediatric Internet-based Discussion Group (PDG) assists health care professionals in resolving HIV-related clinical problems through the use of case studies. Summaries of difficult and interesting cases are emailed to group members who email their responses to all participants. This format allows users to consult with one another, share their experiences, and utilize their collective expertise in the treatment of HIV and HIV-related illnesses in an online forum. The following case was presented to a group of South African pediatricians. The opinions of the participants are summarized below, followed by recommendations from experts in the field. Readers should be aware that opinions vary and may be influenced by the availability of resources and differences in standard of care among regions. Clinical judgment, reinforced by data, is of paramount importance .

transparent gif

The Case

transparent gif

This case involves a 2-year-old boy born to HIV-negative parents in a country in southern Africa. Both parents are HIV negative. The child was very healthy in his first year of life, but he has been recurrently ill since he was 13 months old. He had malaria and pneumonia once, had bronchitis 3 times, and has an enlarged gland in his neck. He was diagnosed with tuberculosis (TB) based on a positive Mantoux test result and was given a 6-month course of isoniazid, rifampin, and pyrazinamide. A chest radiograph revealed nothing abnormal.

The boy was a full-term, healthy baby with no complications at birth, and he has never received a blood transfusion. His developmental milestones have been normal.

Clinicians in the child's home country conducted an HIV enzyme-linked immunosorbent assay (ELISA), which yielded a positive result. A Western blot test sample was sent to South Africa for analysis, and the result also was positive.

The child's weight and height are both just below the 3rd percentile. He has shotty axillary lymph nodes. His chest is normal. There is no visceromegaly.

Results of blood tests to assess the need for antiretroviral treatment were as follows:

  • CD4 count: 1,219 cells/µL (CD4 percentage: 38.5%)

  • Viral load: <50 copies/µL

  • Hemoglobin: 12.6 g/dL

  • White blood cell count: 6.5 IU/µL

  • Platelet count: 271,000 cells/µL

Participants were asked to consider the following questions:

  1. What treatment should be initiated?

  2. What further tests should be performed?

  3. If both parents are HIV negative, how could this child have acquired HIV?

Participants:

Princess Nakedi Miriam Adhikari Liz Walters
James Nuttall Michelle Meiring Frederick Sinyinza
Chifumbe Chintu Lynne Webber Didier Kangudie
Mark Paterson Claire Egbers Danielle Crida
Daniel Soji Mutsa Bwakura Jane Fleet
Simon Schaaf Kevi Naidu Bakani Thipe
Jodie Howard Pierre Kariyo Cliff Ferreira
Omar Farouk Jooma Harry Moultrich Angelina Kakooza Mwesige
transparent gif
transparent gif

Question 1: What treatment should be initiated?

transparent gif

This question was difficult for most participants to answer definitively. It is very unusual for an HIV-positive child who is treatment naive to have an undetectable viral load at age 2. Most participants felt there were too many unanswered questions about the child's diagnoses to initiate antiretroviral treatment (ART) without conducting more extensive tests or repeating previous tests. Some suggested treating the child with cotrimoxazole until HIV infection could be excluded. One participant noted that, if the child were indeed HIV infected, he would be considered a clinical stage 3 patient according to the World Health Organization classification system, because of the presence of TB. Many wondered whether the large cervical node had disappeared with TB treatment. This would be indicative of TB lymphadenitis, thus qualifying the child for ART. Most participants recommended nutritional support for the child. Deworming and micronutrient supplementation, particularly with vitamin A and folic acid, also were suggested.

transparent gif

Question 2: What further tests should be performed?

transparent gif

Most care providers felt that, without repeat HIV testing, the child should not be started on ART. Because it is so unusual to see a treatment-naive young child with an undetectable viral load, most participants felt strongly that additional HIV tests should be performed. Some suggested repeat serologic testing (both ELISA and Western blot) using different test kits. Others suggested HIV DNA polymerase chain reaction (PCR) tests with primers looking for specific strains of HIV that are endemic to the child's home country. At the very least, it was felt that the child's CD4 cell counts/percentages should be monitored every 3-4 months.

The child's shotty nodes troubled the participants. Most participants suggested performing a node biopsy.

Regarding the child's history of TB, participants wanted more information about the positive smear test result. Many asked whether the child had received a bacillus Calmette-Guérin (BCG) vaccination at birth. It was noted that the vaccination could still affect the result of a Mantoux test for a 2-year-old. Some participants wanted to know the size of induration.

Participants suggested tests for hereditary hypergammaglobulinemia (abnormal beta/thymic cells) and rapid plasma reagin screening to check for syphilis and molluscum contagiosum virus, because of the child's previous malaria. Many felt that cytomegalovirus also must be excluded. Additionally, physicians wanted to perform liver function tests, ultrasound scanning of the abdomen, renal function tests, and urinalysis.

transparent gif

Question 3: If both parents are HIV negative, how could this child have acquired HIV?

transparent gif

Based on the assumption that the child's positive HIV test results were accurate, most participants suggested that the source of the HIV infection was breast-feeding. Most likely, this would have resulted from wet-nursing. Some participants suggested that the child's mother could have been infected after her initial HIV test. Others suggested that the child could have been a victim of child-swapping or sexual abuse. It was also posited that the child could have contracted HIV from contaminated needles used for vaccinations or from infusion sets during his previous hospitalizations.

transparent gif

Expert Opinions

transparent gif

After the participants discussed the case and contributed their suggestions for treating the patient, the details were presented to a panel of experts. The members of the panel were:

  • Shaffiq Essajee, MD --Clinical Assistant Professor, Department of Pediatrics (Infectious Disease), New York University; Member, NYU Pediatric Infectious Disease and Immunology

  • George McSherry, MD --Associate Professor, Department of Pediatrics, New Jersey Medical School, School of Medicine and Dentistry of New Jersey

  • Karyn Moshal, MD --Doctor of Infectious Diseases and HIV, Great Ormond Street Hospital for Children, London; Infectious Diseases Consultant

All the experts consulted felt that the HIV diagnosis was still unclear and strongly recommended retesting the parents and the child. Whether or not the child was the biological child of the parents, the experts all thought that such a low viral load in a perinatally infected symptomatic 2-year-old child who was not on treatment was greatly puzzling. Even if the child had been infected postnatally through wet-nursing, iatrogenic scarification, or uvulectomy (seen commonly in Kenya), the case still seemed most unusual. All felt that, most likely, they were seeing a false-positive case and recommended repeating the viral load test or performing an Amplicor V 1.5 DNA PCR assay.

The possibility that the child might be infected with HIV-2 was raised, and it was noted that HIV-2-specific ELISA tests were available. It was suggested that if all other tests results were negative, the child should be tested specifically for HIV-2. The experts also felt that syphilis testing should be conducted.

The experts noted that the TB diagnosis also was not definitive. Technically, the child's condition as described was not pulmonary TB but scrofula, which would mean that the child had not reached WHO clinical stage 3 and, therefore, was not eligible for ART.

According to the experts, the shotty lymph nodes were not consistent with TB infection and the positive Mantoux test could have resulted from a neonatal BCG vaccination. It was noted that TB in a cervical lymph node could be indicative of mediastinal lymphadenopathy, which would imply pulmonary disease, if not parenchymal disease. Dr. Essajee noted that there is an important immunologic difference between a child who is able to "contain" a TB infection to the chest and cervical nodes, staving off frank pneumonia, and one who cannot contain the infection.

All the experts recommended that the clinicians continue to work up the child for other illnesses, and to treat him for malnutrition in addition to looking further into his TB diagnosis and retesting him and his parents for HIV. Dr. Moshal wondered about other aggravating factors in the child's life that could be contributing to his poor growth. A node biopsy was the only biopsy that the experts thought might be useful. All recommended delaying ART until further testing was completed.

transparent gif

Follow-Up

transparent gif

This case was different from many of the other cases presented to the Paediatric Internet-based Discussion Group. Unlike most, this case generated more questions than answers. The purpose of the group discussion is not to add confusion; thus, Leon Levin, MD, the group moderator, followed up on this case. The following is a synopsis of the follow-up research conducted by Dr. Levin:

It is not unusual to see an undetectable viral load in an HIV-positive adult patient who is not receiving ART. However, as many participants have pointed out, it is highly unusual in a pediatric patient, especially a young one. In infants who acquire HIV perinatally, viral loads climb swiftly to very high levels within 1-2 months after birth and decline slowly over the next 5-6 years. It is extremely unusual to have a viral load of <40 copies/µL in an untreated 2-year-old. For this reason, my primary concern (as with everyone else) was that this child's HIV test results had been false positives. Clinicians performed an HIV qualitative PCR test that yielded a negative result, as did a repeat HIV ELISA.

Now that we could reassure the parents that their child was indeed HIV negative, we still had to explain the positive HIV ELISA result in their home country as well as the positive Western blot result in South Africa. The Western blot result was returned from a reputable laboratory in South Africa, Lab A. I contacted a pathologist at Lab A and was informed that the testing analysis had been outsourced to another reputable laboratory in South Africa, Lab B. The pathologist promised to contact Lab B. According to Lab B, the result was definitely negative, but the information conveyed to Lab A mistakenly indicated a positive result.

I was not able to follow up on the false-positive HIV ELISA result from the home country as I did not have a hard copy of the report. I can only assume that it was a rapid test, which is more prone to result in false positives.

Thus, the mystery of the false-positive results was solved. I think the lesson of this case is that, no matter how careful they are, laboratories do make mistakes sometimes. It is important to follow up on your hunches if you are uncomfortable about some aspect of a case. The parents in this case were able to return to their homeland satisfied that their child did not have HIV. Obviously, there were other issues that needed to be sorted out, including the child's nutritional status, but at least it could be determined that the child was uninfected.

transparent gif

Conclusion: Women, Children, and HIV Analysis

transparent gif

Though the ELISA is the most commonly used test for primary diagnosis of HIV in the United States, it is not sufficient for a definitive diagnosis. A Western blot must always be performed to confirm a reactive ELISA. In much of Africa, ELISA is the only test available. The U.S. Centers for Disease Control and Prevention (CDC) recommends retesting a positive (reactive) ELISA sample twice; if either retest is reactive, then a confirmatory test is performed. Only when the confirmatory test is also reactive is the result reported as HIV positive. It is very possible that the confirmatory test is not always performed in resource-poor settings.

As HIV testing becomes more widespread as a result of rising demand and improved availability, it is essential that health care systems continue to carefully enforce quality control measures. These measures include not only testing the accuracy of kits using known negative and positive controls but also adhering strictly to procedures for recording results and transmitting them to requesting physicians. ELISA testing and Western blot confirmation are usually performed in large hospitals or central reference laboratories in resource-poor countries. Other facilities use rapid HIV antibody tests exclusively. As with a positive ELISA result, a positive rapid antibody test result requires confirmation. Regardless of the screening procedures used, if the clinical history and clinical examination do not fully support a diagnosis of HIV infection, HIV testing should be repeated. A false diagnosis of HIV infection can cause psychological distress and lead to unwarranted treatment with antiretrovirals and significant drug toxicities.

transparent gif
space
transparent gif