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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Diagnosis of HIV Infection in Infants and Children
(Last updated: March 5, 2015; last reviewed: March 5, 2015)
Panel's Recommendations for Diagnosis of HIV Infection in Infants and Children
Virologic assays that directly detect HIV must be used to diagnose HIV infection in infants younger than 18 months; antibody tests should not be used (AII).
HIV RNA and HIV DNA nucleic acid tests (NATs) are recommended as preferred virologic assays (AII).
Virologic diagnostic testing in infants with known perinatal HIV exposure is recommended at ages 14 to 21 days, 1 to 2 months, and 4 to 6 months (AII).
Virologic diagnostic testing at birth should be considered for infants at high risk of HIV infection (AIII).
Virologic diagnostic testing should be considered 2 to 4 weeks after cessation of antiretroviral (ARV) prophylaxis for infants receiving combination ARV infant prophylaxis, if the results of prior virologic testing were negative while the infant was receiving prophylaxis (BIII).
A positive virologic test should be confirmed as soon as possible by a repeat virologic test on a second specimen (AII).
Definitive exclusion of HIV infection in non-breastfed infants is based on two or more negative virologic tests, with one obtained at age ≥1 month and one at age ≥4 months, or two negative HIV antibody tests from separate specimens obtained at age ≥6 months (AII).
Some experts confirm the absence of HIV infection at 12 to 18 months of age in infants with prior negative virologic tests by performing an antibody test to document loss of maternal HIV antibodies (BIII).
Children with perinatal HIV exposure aged 18 to 24 months may have residual maternal HIV antibodies; definitive exclusion or confirmation of HIV infection in children in this age group who are HIV antibody-positive should be based on a NAT (see Diagnostic Testing in Children with Perinatal HIV Exposure in Special Situations) (AII).
Diagnosis of HIV infection in children with non-perinatal exposure or children with perinatal exposure aged >24 months relies primarily on the use of HIV antibody tests; when acute HIV infection is suspected, testing with an HIV NAT may be necessary to diagnose HIV infection (AII).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children† with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children† from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children† from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion
† Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents
Diagnostic Testing in Infants with Perinatal HIV-1 (HIV) Exposure
HIV infection can be definitively diagnosed through use of virologic assays in most non-breastfed HIV-exposed infants by age 1 month and in virtually all infected infants by age 4 months. Tests for antibodies to HIV, including newer tests, do not establish the presence of HIV infection in infants because of transplacental transfer of maternal antibodies to HIV; therefore, a virologic test should be used.1,2 Positive virologic tests (i.e., nucleic acid tests [NAT]—a class of tests that includes HIV DNA and RNA polymerase chain reaction [PCR] assays, and related RNA qualitative or quantitative assays) indicate likely HIV infection. The first test result should be confirmed as soon as possible by a repeat virologic test on a second specimen because false-positive results can occur with both RNA and DNA assays.
HIV culture is not used for routine HIV diagnostic testing.3 It is more complex and expensive to perform than DNA PCR or RNA assays, requires 2 to 4 weeks for definitive results, and is generally not available outside of research laboratories. Use of the currently approved HIV p24 antigen assay is not recommended for infant diagnosis in the United States because the sensitivity and specificity of the assay in the first months of life are less than that of other HIV virologic tests.4,5
Infants who are found to have positive HIV antibody tests but whose mothers’ HIV status is unknown (see Identification of Perinatal HIV Exposure) should be assumed to be HIV-exposed and undergo the HIV diagnostic testing described here.6
HIV DNA PCR
HIV DNA PCR is a sensitive technique used to detect specific HIV viral DNA in peripheral blood mononuclear cells. The specificity of the HIV DNA PCR is 99.8% at birth and 100% at ages 1, 3, and 6 months. The sensitivity of the test performed at birth is 55% but increases to more than 90% by 2 to 4 weeks of age and to 100% at ages 3 months and 6 months.6-9 Although, the AMPLICOR® HIV-1 DNA test has been widely used for diagnosis of infants born to HIV-1-infected mothers since it was introduced in 1992, it is no longer commercially available in the United States. The sensitivity and specificity of non-commercial HIV-1 DNA tests (using individual laboratory reagents) may differ from the sensitivity and specificity of the Food and Drug Administration (FDA)-approved commercial test.
HIV RNA Assays
HIV quantitative RNA assays detect extracellular viral RNA in the plasma. Their specificity (for results ≥5,000 copies/mL) has been shown to be 100% at birth and at 1, 3, and 6 months of age and is comparable to HIV DNA PCR.8 HIV RNA levels <5,000 copies/mL may not be reproducible and should be repeated before they are interpreted as documenting HIV infection in an infant. The sensitivity of HIV RNA assays has been shown to be 25% to 58% during the first weeks of life, 89% at age 1 month, and 90% to 100% by age 2 to 3 months.6-8 HIV RNA assays were found to be as sensitive as HIV DNA PCR for early diagnosis of HIV infection in HIV-exposed infants regardless of receipt of infant zidovudine prophylaxis.6,8
An HIV RNA assay can be used as the supplemental test for infants who have an initial positive HIV DNA PCR test. In addition to providing virologic confirmation of infection status, the expense of repeat HIV DNA PCR testing is spared and an HIV RNA measurement is available to assess baseline viral load. HIV RNA assays may be more sensitive than HIV DNA PCR for detecting HIV non-subtype B (see Issues Related to Diagnosis of Group M Non-Subtype B and Group O HIV-1 Infections).
While HIV DNA PCR remains positive in most individuals receiving antiretroviral (ARV) treatment, HIV RNA assays could potentially be affected by maternal antenatal treatment or infant combination ARV prophylaxis.8,10 However, in one study, the sensitivity of HIV RNA assays was not associated with the type of maternal or infant ARV prophylaxis, but HIV RNA levels at 1 month were significantly lower in infants receiving multidrug prophylaxis (n = 9) compared to levels among infected infants receiving single-drug zidovudine prophylaxis (n = 47) (median HIV RNA 2.5 log copies/mL vs. 5.4 log copies/mL, respectively). In contrast, the median HIV RNA levels were high (median HIV RNA 5.6 log copies/mL) by age 3 months in both groups after stopping prophylaxis.8 Further studies are necessary to evaluate the sensitivity of HIV RNA assays during and after receipt of combination infant ARV prophylaxis.
The HIV qualitative RNA assay (APTIMA HIV-1 RNA Qualitative Assay) is an alternative diagnostic test that can be used for infant testing. It is the only qualitative RNA test that is FDA-approved.9,11-15
Issues Related to Diagnosis of Group M Non-Subtype B and Group O HIV-1 Infections
Although HIV-1 Group M subtype B is the predominant viral subtype found in the United States, non-subtype B viruses predominate in other parts of the world, such as subtype C in regions of Africa and India and subtype CRF01 in much of Southeast Asia. Group O HIV strains are seen in West-Central Africa. Non-subtype B and Group O strains may also be seen in countries with links to these geographical regions.16-19 Geographical distribution of HIV groups is available at http://www.hiv.lanl.gov/components/sequence/HIV/geo/geo.comp.
HIV DNA PCR tests have decreased sensitivity for detection of non-subtype B HIV, and false-negative HIV DNA PCR test results have been reported in infants infected with non-subtype B HIV.20-22 In an evaluation of perinatally infected infants diagnosed in New York State in 2001 through 2002, 16.7% of infants were infected with a non-subtype B strain of HIV, compared with 4.4% of infants diagnosed between 1998 and 1999.23
When evaluating an infant whose mother’s HIV transmission risk is linked to an area endemic for non-subtype B HIV or Group O strains, such as Africa or Southeast Asia, clinicians should consider conducting initial testing using one of the assays more sensitive for non-subtype B viruses, such as one of the real-time PCR assays or the qualitative RNA assay. In addition, when non-subtype B perinatal exposure is suspected in infants with negative HIV DNA PCR results, repeat testing using one of the newer RNA assays is recommended. The child should undergo close clinical monitoring and HIV serologic testing at age 18 months to definitively rule out HIV infection. Clinicians should consult with an expert in pediatric HIV infection; state or local public health departments or the Centers for Disease Control and Prevention (CDC) may be able to assist in obtaining referrals for diagnostic testing.
Issues Related to Diagnosis of HIV-2 Infections
HIV-2 infection is endemic in Angola; Mozambique; West African countries including Cape Verde, Ivory Coast, Gambia, Guinea-Bissau, Mali, Mauritania, Nigeria, Sierra Leone, Benin, Burkina Faso, Ghana, Guinea, Liberia, Niger, Nigeria, Sao Tome, Senegal, and Togo; and parts of India.30,31 It also occurs in countries such as France and Portugal, which have large numbers of immigrants from these regions;32,33 HIV-2 is rare in the United States. HIV-2 infection should be suspected in pregnant women who are from—or who have partners from—countries in which the disease is endemic, who are HIV-1 antibody-positive on an initial immunoassay test, and who have repeatedly indeterminate results on HIV-1 Western blot and HIV-1 RNA viral loads at or below the limit of detection.34,35 This pattern of HIV testing can also be seen in patients who have a false-positive HIV antibody test. HIV-1 and HIV-2 coinfections may also occur but are rare outside areas where HIV-2 is endemic. Although accurate diagnosis of HIV-2 can be problematic, it is clinically important because HIV-2 strains are naturally resistant to several ARV drugs developed to suppress HIV-1.36
The majority of commercially available HIV screening antibody tests can detect both HIV-1 and HIV-2 but do not distinguish between the two viruses. More than 60% of individuals with HIV-2 infection are misclassified as having HIV-1 by the HIV-1 Western blot. The only FDA-approved antibody test that distinguishes between HIV-1 and HIV-2 is the Bio-Rad Laboratories Multispot HIV-1/HIV-2 rapid test which, in the United States, is being used increasingly as a supplemental test instead of the Western blot. All HIV-2 cases should be reported to the HIV surveillance program of the state or local health department, which can arrange for additional confirmatory testing for HIV-2 by their public health laboratory or the CDC. Confirmatory testing for HIV-2 infection uses an HIV-2 nucleic acid test. HIV-2 RNA is undetectable in at least half of HIV-2-infected persons; thus, tests for HIV-2 proviral DNA may be necessary for definitive diagnosis.37-39
Infants born to HIV-2-infected mothers should be tested for HIV-2 infection with HIV-2-specific virologic assays (HIV-2 DNA PCR testing) at time points similar to those used for HIV-1 testing. HIV-2 virologic assays are not commercially available, but the National Perinatal HIV Hotline (1-888-448-8765) can provide a list of sites that perform this testing. Clinicians should consult with an expert in pediatric HIV infection when caring for infants with suspected or known exposure to HIV-2.30,40,41
Timing of Diagnostic Testing in Infants with Known Perinatal HIV Exposure
Virologic diagnostic testing of an HIV-exposed infant should be performed at age 14 to 21 days, at age 1 to 2 months, and at age 4 to 6 months. Virologic diagnostic testing should be considered at birth for infants at high risk of HIV infection and 2 to 4 weeks after discontinuation of prophylaxis for infants receiving combination neonatal ARV regimens (see below).
Confirmation of HIV infection should be based on two positive virologic tests from separate blood samples, regardless of a child’s age. A positive HIV antibody test with supplemental Western blot (or immunofluorescent antibody [IFA] assay) at age ≥18 months generally confirms HIV infection; exceptions include late seroreverters (see Diagnostic Testing in Children with Perinatal HIV Exposure in Special Situations).1
HIV infection can be presumptively excluded in non-breastfed infants with two or more negative virologic tests (one at age ≥14 days and one at age ≥4 weeks) or one negative virologic test (i.e., negative NAT [RNA or DNA]) test at age ≥8 weeks, or one negative HIV antibody test at age ≥6 months.1,6Pneumocystis jirovecii pneumonia (PCP) prophylaxis is recommended for infants with indeterminate HIV infection status starting at age 4 to 6 weeks until they are determined to be HIV-uninfected or presumptively uninfected.42 Thus, initiation of PCP prophylaxis can be avoided or discontinued if an infant has negative virologic tests at ages 2 weeks and ≥4 weeks, or if virologic testing is negative at age ≥8 weeks.
Definitive exclusion of HIV infection in a non-breastfed infant is based on two or more negative virologic tests (i.e., negative NATs [RNA or DNA]), one at age ≥1 month and one at age ≥4 months, or two negative HIV antibody tests from separate specimens obtained at age ≥6 months. For both presumptive and definitive exclusion of HIV infection, a child must have no other laboratory (i.e., no positive virologic test results or low CD4 T lymphocyte [CD4] cell count/percent) or clinical evidence of HIV infection and not be breastfeeding. Many experts confirm the absence of HIV infection in infants with negative virologic tests by performing an antibody test at age 12 to 18 months to document seroreversion to HIV antibody-negative status.
Virologic Testing at Birth (Optional)
Virologic testing at birth should be considered for newborns at high risk of perinatal HIV transmission, such as infants born to HIV-infected mothers who did not receive prenatal care or prenatal ARVs, were diagnosed with acute HIV infection during pregnancy, or who had HIV viral loads >1,000 copies/mL close to the time of delivery.43,44 As many as 30% to 40% of HIV-infected infants can be identified by age 48 hours.6 Prompt diagnosis is critical to allow for discontinuing ARV prophylaxis and instituting early ARV therapy (see When to Initiate Therapy). Blood samples from the umbilical cord should not be used for diagnostic evaluations because of the potential for contamination with maternal blood. Working definitions have been proposed to differentiate acquisition of HIV infection in utero from the intrapartum period. Infants who have a positive virologic test at or before age 48 hours are considered to have early (i.e., intrauterine) infection, whereas infants who have a negative virologic test during the first week of life and subsequent positive tests are considered to have late (i.e., intrapartum) infection.44-46
Infants with negative virologic tests before age 1 month should be retested at age 1 to 2 months. Most HIV-exposed neonates will receive 6 weeks of neonatal ARV prophylaxis. Although the use of antepartum, intrapartum, and neonatal zidovudine single-drug prophylaxis did not delay detection of HIV by culture in infants in Pediatric AIDS Clinical Trials Group protocol 076 or affect the sensitivity and predictive values of many virologic assays,6,47,48 this may not always apply to current combination prenatal and neonatal ARV regimens if the test is obtained while the infant is receiving combination neonatal ARV prophylaxis.8
Virologic diagnostic testing for infants receiving combination ARV infant prophylaxis should be considered 2 to 4 weeks after cessation of prophylaxis if prior negative diagnostic testing was performed during the period of prophylaxis. In such situations, the test recommended at age 1 to 2 months can be delayed until after cessation of ARV prophylaxis.
An infant with two negative virologic tests, one at age ≥14 days and one at age ≥1 month, can be viewed as presumptively uninfected and will not need PCP prophylaxis, assuming the child has not had a positive virologic test, CD4 immunosuppression, or clinical evidence of HIV infection.
Virologic Testing at Age 4 to 6 Months
HIV-exposed children who have had negative virologic assays at age 14 to 21 days and at age 1 to 2 months, have no clinical evidence of HIV infection, and are not breastfed should be retested at age 4 to 6 months for definitive exclusion of HIV infection.
Antibody Testing at Age 6 Months and Older
Two or more negative HIV antibody tests performed in non-breastfed infants at age ≥6 months can also be used to definitively exclude HIV infection in HIV-exposed children with no clinical or virologic laboratory evidence of HIV infection.
Antibody Testing at Age 12 to 18 Months to Document Seroreversion
Some experts confirm the absence of HIV infection in infants with negative virologic tests (when there has not been prior confirmation of two negative antibody tests) by repeat serologic testing between 12 and 18 months of age to confirm that maternal HIV antibodies transferred in utero have disappeared.1 In a recent study, the median age at seroreversion was 13.9 months.49 Although the majority of HIV-uninfected infants will serorevert by age 15 to 18 months, there are reports of late seroreversion after 18 months (see below). Factors that might influence the time to seroreversion include maternal disease stage and assay sensitivity.49-52
Diagnostic Testing in Children with Perinatal HIV Exposure in Special Situations
Late Seroreversion up to Age 24 Months
Non-breastfed, perinatally HIV-exposed infants with no other HIV transmission risk and no clinical or virologic laboratory evidence of HIV infection may have residual HIV antibodies up to age 24 months (these infants are called late seroreverters).50,52-54 In one study, 14% seroreverted after age 18 months.49 These children may have positive immunoassay results but indeterminate supplemental antibody tests (using Western blot or IFA). In such cases, repeat antibody testing at a later time would document seroreversion. Due to the possibility of residual HIV antibodies, virologic testing (i.e., with a NAT) will be necessary to definitively exclude or confirm HIV infection in children with perinatal HIV exposure at age 18 to 24 months in situations such as lack of prior testing history or clinical suspicion of HIV infection.
Postnatal HIV Infection in HIV-Exposed Children with Prior Negative Virologic Tests for Whom There Are Additional HIV Transmission Risks
In contrast to late seroreverters, in rare situations postnatal HIV infections have been reported in HIV-exposed infants who had prior negative HIV virologic tests. This occurs in infants who become infected through an additional risk after completion of testing (see Diagnostic Testing in Children with Non-Perinatal HIV Exposure or Children with Perinatal Exposure Aged >24 Months). If an HIV antibody test is positive at age 18 to 24 months, repeated virologic testing will distinguish between residual antibodies in uninfected, late-seroreverting children and true infection.
Suspicion of HIV-2 or Non-Subtype B HIV-1 Infections with False-Negative Virologic Test Results
Children with non-subtype B HIV-1 infection and children with HIV-2 infection may have false-negative virologic tests but persistent positive immunossay results and indeterminate HIV-1 Western blot results.20-22 The diagnostic approach in these situations is discussed above in the sections in Issues Related to Diagnosis of Group M Non-Subtype B and Group O HIV-1 Infections and in Issues Related to Diagnosis of HIV-2 Infections.
Diagnostic Testing in Children with Non-Perinatal HIV Exposure or Children with Perinatal Exposure Aged >24 Months
Breastfeeding is a known route of postnatal HIV transmission. Typical scenarios in the United States include women who have not been adequately counseled about infant feeding, women who breastfeed despite being counseled not to do so (this may occur among women from communities where breastfeeding is the norm and/or in women who fear that not breastfeeding would be a stigma or would reveal their HIV status), and women who learn of their HIV diagnosis only after initiating breastfeeding (such as women who were HIV negative during pregnancy but who acquire HIV infection postnatally; breastfeeding during acute HIV infection is associated with an increased risk of perinatal HIV transmission).55-57 Donor breast milk from an unscreened HIV-infected donor is an additional potential risk factor. Diagnostic testing to rule out acquisition of HIV through breast milk will only be accurate after breastfeeding has completely ceased. Infants who are breastfed by HIV-infected women should undergo immediate age-appropriate HIV diagnostic testing, and breastfeeding should be discontinued. Follow-up testing should be performed at 4 to 6 weeks, 3 months, and 6 months after breastfeeding cessation if the initial tests are negative.58,59 HIV antibody testing of an infant to assess for HIV exposure would not be helpful if the mother acquired HIV infection after giving birth. In that situation, an infant would be HIV antibody-negative but still at risk of acquiring HIV infection through breastfeeding, and counseling to cease breastfeeding should be provided.
Receipt of solid food premasticated or prechewed by an HIV-infected caregiver has been documented to be associated with risk of HIV transmission.53,54,60-63 If this occurs in perinatally HIV-exposed infants 24 months or younger with prior negative virologic tests, it will be necessary for such children to undergo virologic diagnostic testing, as they may have residual maternal HIV antibody (see Diagnostic Testing in Children with Perinatal HIV Exposure in Special Situations).
Additional routes of HIV transmission in children include sexual abuse or receipt of contaminated blood products (which occurs in countries in which parenteral exposure to HIV via contaminated blood products is a possibility). In such cases, maternal HIV status may be negative or unknown.
Acquisition of HIV is possible through accidental needlesticks or behavioral risks, such as sexual activity or injection drug use in older children. Medical procedures performed in settings with inadequate infection control practices may pose a potential risk; although tattooing or body piercing presents a potential risk of HIV transmission, no cases of HIV transmission from these activities have been documented.64
Diagnosis of HIV-1 infection in children with non-perinatal exposure or children with perinatal exposure aged >24 months relies primarily on HIV antibody tests.1 FDA-approved diagnostic tests include:
Antigen/antibody combination immunoassays (fourth-generation tests) that detect HIV-1/2 antibodies as well as HIV-1 p24 antigen: Recommended for initial testing
HIV-1/2 immunoassays (third-generation antibody tests): Alternative for initial testing
HIV-1/HIV-2 antibody differentiation immunoassay that differentiates HIV-1 antibodies from HIV-2 antibodies (Multispot HIV-1/HIV-2 test): Recommended for supplemental testing
HIV-1 Western blot and HIV-1 indirect IFAs (first-generation tests): Alternative for supplemental testing
HIV-1 NAT (HIV qualitative RNA assay)
If acute HIV infection or end-stage AIDS is suspected, virologic testing may be necessary to diagnose HIV infection because HIV-1/2 antibody immunoassays, HIV-1 Western blot, or HIV-1 IFA may be negative in these situations.
Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Available at http://stacks.cdc.gov/view/cdc/23447. Published June 27, 2014. Accessed December 2, 2014.
Donovan M, Palumbo P. Diagnosis of HIV: challenges and strategies for HIV prevention and detection among pregnant women and their infants. Clin Perinatol. 2010;37(4):751-763, viii. Available at http://www.ncbi.nlm.nih.gov/pubmed/21078448.
McIntosh K, Pitt J, Brambilla D, et al. Blood culture in the first 6 months of life for the diagnosis of vertically transmitted human immunodeficiency virus infection. The Women and Infants Transmission Study Group. J Infect Dis. 1994;170(4):996-1000. Available at http://www.ncbi.nlm.nih.gov/pubmed/7930747.
Tamhane M, Gautney B, Shiu C, et al. Analysis of the optimal cut-point for HIV-p24 antigen testing to diagnose HIV infection in HIV-exposed children from resource-constrained settings. J Clin Virol. 2011;50(4):338-341. Available at http://www.ncbi.nlm.nih.gov/pubmed/21330193.
Wessman MJ, Theilgaard Z, Katzenstein TL. Determination of HIV status of infants born to HIV-infected mothers: a review of the diagnostic methods with special focus on the applicability of p24 antigen testing in developing countries. Scand J Infect Dis. 2012;44(3):209-215. Available at http://www.ncbi.nlm.nih.gov/pubmed/22074445.
Havens PL, Mofenson LM, American Academy of Pediatrics Committee on Pediatric A. Evaluation and management of the infant exposed to HIV-1 in the United States. Pediatrics. 2009;123(1):175-187. Available at http://www.ncbi.nlm.nih.gov/pubmed/19117880.
American Academy of Pediatrics Committee on Pediatric AIDS. HIV testing and prophylaxis to prevent mother-to-child transmission in the United States. Pediatrics. 2008;122(5):1127-1134. Available at http://www.ncbi.nlm.nih.gov/pubmed/18977995.
Burgard M, Blanche S, Jasseron C, et al. Performance of HIV-1 DNA or HIV-1 RNA tests for early diagnosis of perinatal HIV-1 infection during anti-retroviral prophylaxis. J Pediatr. 2012;160(1):60-66 e61. Available at http://www.ncbi.nlm.nih.gov/pubmed/21868029.
Lilian RR, Kalk E, Bhowan K, et al. Early diagnosis of in utero and intrapartum HIV infection in infants prior to 6 weeks of age. J Clin Microbiol. 2012;50(7):2373-2377. Available at http://www.ncbi.nlm.nih.gov/pubmed/22518871.
Saitoh A, Hsia K, Fenton T, et al. Persistence of human immunodeficiency virus (HIV) type 1 DNA in peripheral blood despite prolonged suppression of plasma HIV-1 RNA in children. J Infect Dis. 2002;185(10):1409-1416. Available at http://www.ncbi.nlm.nih.gov/pubmed/11992275.
Kerr RJ, Player G, Fiscus SA, Nelson JA. Qualitative human immunodeficiency virus RNA analysis of dried blood spots for diagnosis of infections in infants. J Clin Microbiol. 2009;47(1):220-222. Available at http://www.ncbi.nlm.nih.gov/pubmed/19005148.
Stevens WS, Noble L, Berrie L, Sarang S, Scott LE. Ultra-high-throughput, automated nucleic acid detection of human immunodeficiency virus (HIV) for infant infection diagnosis using the Gen-Probe Aptima HIV-1 screening assay. J Clin Microbiol. 2009;47(8):2465-2469. Available at http://www.ncbi.nlm.nih.gov/pubmed/19474266.
Walter J, Kuhn L, Semrau K, et al. Detection of low levels of human immunodeficiency virus (HIV) may be critical for early diagnosis of pediatric HIV infection by use of dried blood spots. J Clin Microbiol. 2009;47(9):2989-2991. Available at http://www.ncbi.nlm.nih.gov/pubmed/19625479.
Pierce VM, Neide B, Hodinka RL. Evaluation of the Gen-Probe Aptima HIV-1 RNA qualitative assay as an alternative to Western blot analysis for confirmation of HIV infection. J Clin Microbiol. 2011;49(4):1642-1645. Available at http://www.ncbi.nlm.nih.gov/pubmed/21346052.
Osmanov S, Pattou C, Walker N, et al. Estimated global distribution and regional spread of HIV-1 genetic subtypes in the year 2000. J Acquir Immune Defic Syndr. 2002;29(2):184-190. Available at http://www.ncbi.nlm.nih.gov/pubmed/11832690.
Auwanit W, Isarangkura-Na-Ayuthaya P, Kasornpikul D, Ikuta K, Sawanpanyalert P, Kameoka M. Detection of drug resistance-associated and background mutations in human immunodeficiency virus type 1 CRF01_AE protease and reverse transcriptase derived from drug treatment-naive patients residing in central Thailand. AIDS Res Hum Retroviruses. 2009;25(6):625-631. Available at http://www.ncbi.nlm.nih.gov/pubmed/19500016.
Deshpande A, Jauvin V, Pinson P, Jeannot AC, Fleury HJ. Phylogenetic analysis of HIV-1 reverse transcriptase sequences from 382 patients recruited in JJ Hospital of Mumbai, India, between 2002 and 2008. AIDS Res Hum Retroviruses. 2009;25(6):633-635. Available at http://www.ncbi.nlm.nih.gov/pubmed/19534630.
Chaix ML, Seng R, Frange P, et al. Increasing HIV-1 non-B subtype primary infections in patients in France and effect of HIV subtypes on virological and immunological responses to combined antiretroviral therapy. Clin Infect Dis. 2013;56(6):880-887. Available at http://www.ncbi.nlm.nih.gov/pubmed/23223603.
Kline NE, Schwarzwald H, Kline MW. False negative DNA polymerase chain reaction in an infant with subtype C human immunodeficiency virus 1 infection. Pediatr Infect Dis J. 2002;21(9):885-886. Available at http://www.ncbi.nlm.nih.gov/pubmed/12380591.
Zaman MM, Recco RA, Haag R. Infection with non-B subtype HIV type 1 complicates management of established infection in adult patients and diagnosis of infection in newborn infants. Clin Infect Dis. 2002;34(3):417-418. Available at http://www.ncbi.nlm.nih.gov/pubmed/11774090.
Obaro SK, Losikoff P, Harwell J, Pugatch D. Failure of serial human immunodeficiency virus type 1 DNA polymerase chain reactions to identify human immunodeficiency virus type 1 clade A/G. Pediatr Infect Dis J. 2005;24(2):183-184. Available at http://www.ncbi.nlm.nih.gov/pubmed/15702052.
Karchava M, Pulver W, Smith L, et al. Prevalence of drug-resistance mutations and non-subtype B strains among HIV-infected infants from New York State. J Acquir Immune Defic Syndr. 2006;42(5):614-619. Available at http://www.ncbi.nlm.nih.gov/pubmed/16868498.
Swanson P, de Mendoza C, Joshi Y, et al. Impact of human immunodeficiency virus type 1 (HIV-1) genetic diversity on performance of four commercial viral load assays: LCx HIV RNA Quantitative, AMPLICOR HIV-1 MONITOR v1.5, VERSANT HIV-1 RNA 3.0, and NucliSens HIV-1 QT. J Clin Microbiol. 2005;43(8):3860-3868. Available at http://www.ncbi.nlm.nih.gov/pubmed/16081923.
Church D, Gregson D, Lloyd T, et al. Comparison of the RealTime HIV-1, COBAS TaqMan 48 v1.0, Easy Q v1.2, and Versant v3.0 assays for determination of HIV-1 viral loads in a cohort of Canadian patients with diverse HIV subtype infections. J Clin Microbiol. 2011;49(1):118-124. Available at http://www.ncbi.nlm.nih.gov/pubmed/21084515.
Katsoulidou A, Rokka C, Issaris C, et al. Comparative evaluation of the performance of the Abbott RealTime HIV-1 assay for measurement of HIV-1 plasma viral load on genetically diverse samples from Greece. Virol J. 2011;8:10. Available at http://www.ncbi.nlm.nih.gov/pubmed/21219667.
Gueudin M, Leoz M, Lemee V, et al. A new real-time quantitative PCR for diagnosis and monitoring of HIV-1 group O infection. J Clin Microbiol. 2012;50(3):831-836. Available at http://www.ncbi.nlm.nih.gov/pubmed/22170927.
Xu S, Song A, Nie J, et al. Comparison between the automated Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 2.0 assay and its version 1 and Nuclisens HIV-1 EasyQ version 2.0 assays when measuring diverse HIV-1 genotypes in China. J Clin Virol. 2012;53(1):33-37. Available at http://www.ncbi.nlm.nih.gov/pubmed/22051503.
Nasrullah M, Ethridge SF, Delaney KP, et al. Comparison of alternative interpretive criteria for the HIV-1 Western blot and results of the Multispot HIV-1/HIV-2 Rapid Test for classifying HIV-1 and HIV-2 infections. J Clin Virol. 2011;52 Suppl 1:S23-27. Available at http://www.ncbi.nlm.nih.gov/pubmed/21993309.
Wesolowski LG, Delaney KP, Hart C, et al. Performance of an alternative laboratory-based algorithm for diagnosis of HIV infection utilizing a third generation immunoassay, a rapid HIV-1/HIV-2 differentiation test and a DNA or RNA-based nucleic acid amplification test in persons with established HIV-1 infection and blood donors. J Clin Virol. 2011;52 Suppl 1:S45-49. Available at http://www.ncbi.nlm.nih.gov/pubmed/21995934.
Shanmugam V, Switzer WM, Nkengasong JN, et al. Lower HIV-2 plasma viral loads may explain differences between the natural histories of HIV-1 and HIV-2 infections. J Acquir Immune Defic Syndr. 2000;24(3):257-263. Available at http://www.ncbi.nlm.nih.gov/pubmed/10969350.
MacNeil A, Sarr AD, Sankale JL, Meloni ST, Mboup S, Kanki P. Direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (HIV-2) infection than in HIV-1 infection. J Virol. 2007;81(10):5325-5330. Available at http://www.ncbi.nlm.nih.gov/pubmed/17329334.
Damond F, Benard A, Balotta C, et al. An international collaboration to standardize HIV-2 viral load assays: results from the 2009 ACHI(E)V(2E) quality control study. J Clin Microbiol. 2011;49(10):3491-3497. Available at http://www.ncbi.nlm.nih.gov/pubmed/21813718.
Burgard M, Jasseron C, Matheron S, et al. Mother-to-child transmission of HIV-2 infection from 1986 to 2007 in the ANRS French Perinatal Cohort EPF-CO1. Clin Infect Dis. 2010;51(7):833-843. Available at http://www.ncbi.nlm.nih.gov/pubmed/20804413.
Lilian RR, Kalk E, Technau KG, Sherman GG. Birth Diagnosis of HIV Infection on Infants to Reduce Infant Mortality and Monitor for Elimination of Mother-to-Child Transmission. Pediatr Infect Dis J. 2013. Available at http://www.ncbi.nlm.nih.gov/pubmed/23574775.
Jourdain G, Mary JY, Coeur SL, et al. Risk factors for in utero or intrapartum mother-to-child transmission of human immunodeficiency virus type 1 in Thailand. J Infect Dis. 2007;196(11):1629-1636. Available at http://www.ncbi.nlm.nih.gov/pubmed/18008246.
Bryson YJ, Luzuriaga K, Sullivan JL, Wara DW. Proposed definitions for in utero versus intrapartum transmission of HIV-1. N Engl J Med. 1992;327(17):1246-1247. Available at http://www.ncbi.nlm.nih.gov/pubmed/1406816.
Kourtis AP, Lee FK, Abrams EJ, Jamieson DJ, Bulterys M. Mother-to-child transmission of HIV-1: timing and implications for prevention. Lancet Infect Dis. 2006;6(11):726-732. Available at http://www.ncbi.nlm.nih.gov/pubmed/17067921.
Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994;331(18):1173-1180. Available at http://www.ncbi.nlm.nih.gov/pubmed/7935654.
Young NL, Shaffer N, Chaowanachan T, et al. Early diagnosis of HIV-1-infected infants in Thailand using RNA and DNA PCR assays sensitive to non-B subtypes. J Acquir Immune Defic Syndr. 2000;24(5):401-407. Available at http://www.ncbi.nlm.nih.gov/pubmed/11035610.
Gutierrez M, Ludwig DA, Khan SS, et al. Has highly active antiretroviral therapy increased the time to seroreversion in HIV exposed but uninfected children? Clin Infect Dis. 2012;55(9):1255-1261. Available at http://www.ncbi.nlm.nih.gov/pubmed/22851494.
Gulia J, Kumwenda N, Li Q, Taha TE. HIV seroreversion time in HIV-1-uninfected children born to HIV-1-infected mothers in Malawi. J Acquir Immune Defic Syndr. 2007;46(3):332-337. Available at http://www.ncbi.nlm.nih.gov/pubmed/17786126.
Alcantara KC, Pereira GA, Albuquerque M, Stefani MM. Seroreversion in children born to HIV-positive and AIDS mothers from Central West Brazil. Trans R Soc Trop Med Hyg. 2009;103(6):620-626. Available at http://www.ncbi.nlm.nih.gov/pubmed/19339030.
Sohn AH, Thanh TC, Thinh le Q, et al. Failure of human immunodeficiency virus enzyme immunoassay to rule out infection among polymerase chain reaction-negative Vietnamese infants at 12 months of age. Pediatr Infect Dis J. 2009;28(4):273-276. Available at http://www.ncbi.nlm.nih.gov/pubmed/19289981.
Gaur AH, Freimanis-Hance L, Dominguez K, et al. Knowledge and practice of prechewing/prewarming food by HIV-infected women. Pediatrics. 2011;127(5):e1206-1211. Available at http://www.ncbi.nlm.nih.gov/pubmed/21482608.
Hafeez S, Salami O, Alvarado M, Maldonado M, Purswani M, Hagmann S. Infant feeding practice of premastication: an anonymous survey among human immunodeficiency virus-infected mothers. Arch Pediatr Adolesc Med. 2011;165(1):92-93. Available at http://www.ncbi.nlm.nih.gov/pubmed/21199989.
Liang K, Gui X, Zhang YZ, Zhuang K, Meyers K, Ho DD. A case series of 104 women infected with HIV-1 via blood transfusion postnatally: high rate of HIV-1 transmission to infants through breast-feeding. J Infect Dis. 2009;200(5):682-686. Available at http://www.ncbi.nlm.nih.gov/pubmed/19627245.
Nesheim S, Harris LF, Lampe M. Elimination of perinatal HIV infection in the USA and other high-income countries: achievements and challenges. Curr Opin HIV AIDS. 2013;8(5):447-456. Available at http://www.ncbi.nlm.nih.gov/pubmed/23925002.
De Schacht C, Mabunda N, Ferreira OC, et al. High HIV incidence in the postpartum period sustains vertical transmission in settings with generalized epidemics: a cohort study in Southern Mozambique. J Int AIDS Soc. 2014;17:18808. Available at http://www.ncbi.nlm.nih.gov/pubmed/24629842.
Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. 2014. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed November 25, 2014.
Centers for Disease Control and Prevention. Premastication of food by caregivers of HIV-exposed children--nine U.S. sites, 2009-2010. MMWR Morb Mortal Wkly Rep. 2011;60(9):273-275. Available at http://www.ncbi.nlm.nih.gov/pubmed/21389930.
Ivy W, 3rd, Dominguez KL, Rakhmanina NY, et al. Premastication as a route of pediatric HIV transmission: case-control and cross-sectional investigations. J Acquir Immune Defic Syndr. 2012;59(2):207-212. Available at http://www.ncbi.nlm.nih.gov/pubmed/22027873.
Gaur AH, Cohen RA, Read JS, et al. Prechewing and prewarming food for HIV-exposed children: a prospective cohort experience from Latin America. AIDS Patient Care STDS. 2013;27(3):142-145. Available at http://www.ncbi.nlm.nih.gov/pubmed/23477456.
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. Centers for Disease Control and Prevention website. http://www.cdc.gov/nchhstp/. Updated December 16, 2014. Accessed December 24, 2014.