The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have developed differing classification systems for pediatric human immunodeficiency virus (HIV)/acquiredimmunodeficiency syndrome (AIDS) (table 2 and table 3 and table 4 and table 5). (See 'Pediatric AIDS case definition' above.)
●The clinical manifestations of pediatric HIV infection are varied and often nonspecific (eg, lymphadenopathy, oral candidiasis, failure to thrive). The most common AIDS-defining conditions in children in the United States include Pneumocystis jirovecii pneumonia (PCP), recurrent bacterial infections, wasting syndrome, candida esophagitis, HIV encephalopathy, and cytomegalovirus. (See 'Clinical manifestations' above.)
●Outcomes of HIV infections depend upon whether effective treatment is provided. Highly effective, combination antiretroviral therapy (ART) has radically reduced mortality and morbidity, particularly incidence of opportunistic infections. (See 'Outcome' above.)
●Without treatment, HIV infection causes progressive immunosuppression, leaving patients at risk of developing opportunistic infections and other HIV-related disorders. Most untreated HIV-infected children die before age five years. However, there is considerable variability, particularly for those with vertically-acquired infection. (See 'Untreated HIV infection' above.)
●Combination ART is associated with improvement in virologic, immunologic, and clinical health for HIV-infected adults and children. The use of combination ART in children has reduced the morbidity and mortality associated with HIV infection in the developed world. However, limited access to adequate health care to sustain widespread HIV diagnosis and treatment has hampered progress in controlling HIV in resource-limited settings. (See 'HIV infection treated with ART' above.)
●Long-term morbidities in children and young adults treated for HIV infection in childhood include mental health concerns, dyslipidemia, insulin resistance and diabetes mellitus, cardiovascular complications, decreased bone mineral density, and renal disease. (See 'Long-term morbidities' above.)
AIDS-defining conditions
| Bacterial infections, multiple or recurrent* |
| Candidiasis of bronchi, trachea, or lungs |
| Candidiasis of esophagus |
| Cervical cancer, invasive¶ |
| Coccidioidomycosis, disseminated or extrapulmonary |
| Cryptococcosis, extrapulmonary |
| Cryptosporidiosis, chronic intestinal (>1 month's duration) |
| Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month |
| Cytomegalovirus retinitis (with loss of vision) |
| Encephalopathy, HIV relatedΔ |
| Herpes simplex: chronic ulcers (>1 month's duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month) |
| Histoplasmosis, disseminated or extrapulmonary |
| Isosporiasis, chronic intestinal (>1 month's duration) |
| Kaposi sarcoma |
| Lymphoma, Burkitt (or equivalent term) |
| Lymphoma, immunoblastic (or equivalent term) |
| Lymphoma, primary, of brain |
| Mycobacterium avium complex (MAC) or Mycobacterium kansasii, disseminated or extrapulmonary |
| Mycobacterium tuberculosis of any site, pulmonary¶, disseminated, or extrapulmonary |
| Mycobacterium, other species or unidentified species, disseminated or extrapulmonary |
| Pneumocystis jirovecii (previously known as "Pneumocystis carinii") pneumonia |
| Pneumonia, recurrent¶ |
| Progressive multifocal leukoencephalopathy |
| Salmonella septicemia, recurrent |
| Toxoplasmosis of brain, onset at age >1 month |
| Wasting syndrome attributed to HIVΔ |
AIDS: acquired immunodeficiency syndrome; HIV: human immunodeficiency virus; MAC: mycobacterium avium complex .
* Only among children aged <6 years.
¶ Only among children aged ≥6 years, adolescents, and adults.
Δ Suggested diagnostic criteria for these illnesses, which might be particularly important for IV encephalopathy and HIV wasting syndrome are described in MMWR Recomm Rep 1994; 43 (No.12) and MMWR Recomm Rep 1992; 41 (No.17).
* Only among children aged <6 years.
¶ Only among children aged ≥6 years, adolescents, and adults.
Δ Suggested diagnostic criteria for these illnesses, which might be particularly important for IV encephalopathy and HIV wasting syndrome are described in MMWR Recomm Rep 1994; 43 (No.12) and MMWR Recomm Rep 1992; 41 (No.17).
Reproduced from: Selik RM, Mokotoff ED, Branson B, et al. Revised Surveillance Case Definition for HIV Infection - United States, 2014. MMWR Recomm Rep 2014; 63:1.
Graphic 59724 Version 6.0
CDC surveillance case definition laboratory criteria for HIV-1 infection
| Persons ≥18 months and children <18 months born to HIV negative mothers |
| HIV infected (one of the following) |
A multitest algorithm consisting of:
|
| A positive result from a multitest HIV antibody algorithm from which only the final result was reported |
A positive result or report of a detectable quantity from any of the following HIV virologic tests:
|
| Children <18 months born to mothers with HIV infection or unknown HIV status |
| HIV infected (all three of the following) |
Positive results on at least one specimen (not including cord blood) from any of the following HIV virologic tests:
|
| The test date is known |
One or both of the following:
|
| Definitively HIV-uninfected (both of the following) |
| No positive HIV NAT (RNA or DNA) |
At least one of the following:
|
| Presumptively HIV-uninfected (all three of the following) |
| Does not meet criteria for definitively uninfected |
Meets at least one of the following four laboratory criteria:
|
| No subsequent NAT |
| Indeterminate |
| Does not meet criteria for HIV-infected or HIV-uninfected (definitive or presumptive) |
CDC: Centers for Disease Control and Prevention; HIV: human immunodeficiency virus; NAT: nucleic acid test.
Selik RM, Mokotoff ED, Branson B, et al. Revised Surveillance Case Definition for HIV Infection - United States, 2014. MMWR Recomm Rep 2014; 63:1.
Graphic 95236 Version 1.0
CDC surveillance case definition HIV infection stage based on age-specific CD4+ T-lymphocyte count or CD4+ T-lymphocyte percentage of total lymphocytes
| Stage | Age at time of CD4+ T-lymphocyte test* | |||||
| <1 year | 1 to 5 years | ≥6 years | ||||
| Cells/microL | Percent | Cells/microL | Percent | Cells/microL | Percent | |
| 0¶ | NA | NA | NA | NA | NA | NA |
| 1 | ≥1500 | ≥34 | ≥1000 | ≥30 | ≥500 | ≥26 |
| 2 | 750 to 1499 | 23 to 33 | 500 to 999 | 22 to 29 | 200 to 499 | 14 to 25 |
| 3 (AIDS)Δ | <750 | <26 | <500 | <22 | <200 | <14 |
| Unknown◊ | NA | NA | NA | NA | NA | NA |
CDC: Centers for Disease Control and Prevention; HIV: human immunodeficiency virus; NA: not applicable; AIDS: acquired immunodeficiency syndrome.
* The CD4+ T-lymphocyte count takes precedence over the CD4 T-lymphocyte percentage; the percentage is considered only if the count is missing.
¶ Stage 0 represents early infection and is defined by a negative or indeterminate HIV test within 180 days before the first confirmed positive HIV test. If the criteria for stage 0 are met, the stage is 0 regardless of criteria for other stages (CD4 T-lymphocyte test results and opportunistic illness diagnoses).
Δ If the criteria for stage 0 are not met and a stage-3-defining opportunistic illness has been diagnosed then the stage is 3 regardless of CD4 T-lymphocyte test results.
◊ If the criteria for stage 0 are not met and information on the above criteria for other stages is missing, then the stage is classified as unknown.
* The CD4+ T-lymphocyte count takes precedence over the CD4 T-lymphocyte percentage; the percentage is considered only if the count is missing.
¶ Stage 0 represents early infection and is defined by a negative or indeterminate HIV test within 180 days before the first confirmed positive HIV test. If the criteria for stage 0 are met, the stage is 0 regardless of criteria for other stages (CD4 T-lymphocyte test results and opportunistic illness diagnoses).
Δ If the criteria for stage 0 are not met and a stage-3-defining opportunistic illness has been diagnosed then the stage is 3 regardless of CD4 T-lymphocyte test results.
◊ If the criteria for stage 0 are not met and information on the above criteria for other stages is missing, then the stage is classified as unknown.
Adapted from: Selik RM, Mokotoff ED, Branson B, et al. Revised Surveillance Case Definition for HIV Infection - United States, 2014. MMWR Recomm Rep 2014; 63:1.
Graphic 95235 Version 3.0
WHO clinical staging of HIV/AIDS for children with confirmed HIV infection
| Clinical stage 1 |
| Asymptomatic |
| Persistent generalized lymphadenopathy |
| Clinical stage 2 |
| Unexplained persistent hepatosplenomegaly |
| Papular pruritic eruptions |
| Fungal nail infection |
| Angular cheilitis |
| Lineal gingival erythema |
| Extensive wart virus infection |
| Extensive molluscum contagiosum |
| Recurrent oral ulcerations |
| Unexplained persistent parotid enlargement |
| Herpes zoster |
| Recurrent or chronic upper respiratory tract infections (otitis media, otorrhea, sinusitis or tonsillitis) |
| Clinical stage 3 |
| Unexplained* moderate malnutrition or wasting not adequately responding to standard therapy |
| Unexplained persistent diarrhea (14 days or more) |
| Unexplained persistent fever (above 37.5°C intermittent or constant, for longer than one month) |
| Persistent oral candidiasis (after first 6 to 8 weeks of life) |
| Oral hairy leukoplakia |
| Acute necrotizing ulcerative gingivitis or periodontitis |
| Lymph node tuberculosis |
| Pulmonary tuberculosis |
| Severe recurrent bacterial pneumonia |
| Symptomatic lymphoid interstitial pneumonitis |
| Chronic HIV-associated lung disease including bronchiectasis |
| Unexplained anaemia (Hgb <8 g/dL), neutropenia (ANC <500 cells/microL (<0.5 × 109/L)) and or chronic thrombocytopenia (PLT <50,000 cells/micoL (<50 × 109 per litre)) |
| Clinical stage 4¶ |
| Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy |
| Pneumocystis pneumonia |
| Recurrent severe bacterial infections (such as empyema, pyomyositis, bone or joint infection or meningitis but excluding pneumonia) |
| Chronic herpes simplex infection (orolabial or cutaneous of more than one month's duration or visceral at any site) |
| Esophageal candidiasis (or candidiasis of trachea, bronchi or lungs) |
| Extrapulmonary tuberculosis |
| Kaposi sarcoma |
| Cytomegalovirus infection: retinitis or cytomegalovirus infection affecting another organ, with onset at age older than one month |
| Central nervous system toxoplasmosis (after one month of life) |
| Extrapulmonary cryptococcosis (including meningitis) |
| HIV encephalopathy |
| Disseminated endemic mycosis (coccidiomycosis or histoplasmosis) |
| Disseminated non-tuberculous mycobacterial infection |
| Chronic cryptosporidiosis (with diarrhea) |
| Chronic isosporiasis |
| Cerebral or B-cell non-Hodgkin lymphoma |
| Progressive multifocal leukoencephalopathy |
| Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy |
Hgb: Hemoglobin; ANC: absolute neutrophil count; PLT: platelet count; WHO: World Health Organization.
* Unexplained refers to where the condition is not explained by other causes.
¶ Some additional specific conditions can also be included in regional classifications (such as reactivation of American trypanosomiasis [meningoencephalitis and/or myocarditis] in the WHO Region of the Americas, disseminated penicilliosis in Asia and HIV-associated rectovaginal fistula in Africa).
¶ Some additional specific conditions can also be included in regional classifications (such as reactivation of American trypanosomiasis [meningoencephalitis and/or myocarditis] in the WHO Region of the Americas, disseminated penicilliosis in Asia and HIV-associated rectovaginal fistula in Africa).
Reprinted from: WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. World Health Organization, Geneva, Switzerland, 2007. Copyright © 2007 World Health Organization.
Graphic 104882 Version 1.0
WHO immunological classification for established HIV infection
| HIV-associated immunodeficiency | Age-related CD4 values | |||
| <11 months (CD4 percent) | 12-35 months (CD4 percent) | 36-59 months (CD4 percent) | >5 years (absolute number per mm3 or CD4 percent) | |
| None or not significant | >35 | >30 | >25 | >500 |
| Mild | 30-35 | 25-30 | 20-25 | 350-499 |
| Moderate | 25-29 | 20-24 | 15-19 | 200-349 |
| Severe | <25 | <20 | <15 | <200 or <15 percent |
CD4 cells expressed as number of cells per mm3 or percentage of total lymphocytes.
WHO: World Health Organization; HIV: human immunodeficiency virus.
Reproduced with permission from: WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. World Health Organization, Geneva, Switzerland, 2007. Copyright © 2007 World Health Organization. http://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf.
Graphic 57988 Version 3.0
Chest radiograph of an HIV-infected 2-year-old boy with Pneumocystis jiroveci pneumonia
Note the presence of bilateral interstitial lung disease, pneumomediastinum, and subcutaneous emphysema.
HIV: human immunodeficiency virus.
Courtesy of Meg Ferris, MD.
Graphic 80631 Version 4.0
Cerebral atrophy in pediatric HIV infection
Head computed tomography (CT) scan in an HIV-infected 8-year-old boy with generalized brain atrophy. Cerebral atrophy is common among children with HIV encephalopathy but is also observed among children with normal neurologic and developmental examinations.
HIV: human immunodeficiency virus.
Courtesy of Meg Ferris, MD.
Graphic 61731 Version 3.0
Funduscopic examination of an HIV-infected 16-year-old girl with cytomegalovirus retinitis
There are extensive areas of hemorrhage with white retinal exudates. Children with cytomegalovirus retinitis usually present with painless visual impairment.
Courtesy of Dr. David Coats, Houston, Texas.
Graphic 60074 Version 2.0
Lymphoid interstitial pneumonia on chest x-ray and CT scan
A chest x-ray (A) shows bilateral non-specific diffuse interstitial coarsening and a cyst in the right lower lobe (arrow). A coronal reconstruction of a CT scan (B) confirms the presence of cysts in the right lower lobe and left upper lobe (arrows). An axial CT scan (C) shows extensive bibasilar cystic changes (dashed arrow) and interstitial thickening (arrow) with changes in the left pleural space (arrowhead) following wedge biopsy. A diagnosis of LIP was confirmed by biopsy.
CT: computed tomography. LIP: Lymphoid interstitial pneumonia
Graphic 89082 Version 1.0
Diagnostic testing for HIV infection in infants and children younger than 18 months
Readily available diagnostic tests that rely on detection of antibody to HIV virus are not reliable in infants and children younger than 18 months of age because of the persistence of transplacentally acquired maternal antibody. Virologic tests are required in babies born to HIV-infected mothers. (See 'Introduction' above.)
●If the maternal HIV status is unknown, serologic testing for HIV should be performed on the mother or infant. If the serologic test is positive, proceed with virologic testing of the infant as for the infant of an HIV-infected mother. (See 'Maternal HIV status unknown' above.)
●In an infant or young child born to an HIV-infected mother, serial HIV virologic testing is required. Qualitative RNA assays are the most commonly available test in the United States, but HIV DNA polymerase chain reactions (PCRs) remain the preferred test in infants in developing settings. (See 'HIV DNA PCR testing' above and 'HIV-infected mother' above.)
•If the mother received appropriate antiretroviral treatment and the infant is at LOW risk for acquiring HIV, testing should be performed at 14 to 21 days, one to two months, and at four to six months of age. A positive result at any point should be confirmed as soon as possible with a repeat virologic test.
•An infant born to a mother who did not receive standard care for an HIV-infected pregnant woman or a woman who was diagnosed with acute HIV during pregnancy should be also tested at birth, as well as 14 to 21 days, one to two months, and four to six months of age. A positive result at any point should be confirmed as soon as possible with a repeat virologic test. This schedule of repeated testing allows for virologic diagnostic testing to be performed two to four weeks after cessation of antiretroviral (ARV) prophylaxis for infants receiving combination ARV infant prophylaxis if the results of virologic testing were negative while the infant was receiving prophylaxis.
●Definitive exclusion of HIV infection in non-breastfed infants requires at least two negative virologic tests: one at ≥1 month of age and one at ≥4 months of age. Some experts recommend a follow up antibody test at 12 to 18 months of age to document clearance of maternal antibody and confirm the child’s HIV-negative status. HIV RNA assays are useful for diagnosing HIV in children born to a mother in the United States who are likely to be infected with a non-clade-B strain of HIV (eg, immigrant from Africa). (See 'HIV RNA assays' above and 'HIV-infected mother' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Heidi Schwarzwald, MD, MPH, who contributed to an earlier version of this topic review.
Prevention of HIV transmission during breastfeeding in resource-limited settings
Mother-to-child HIV-1 transmission occurs in utero, peripartum, and postnatally via breastfeeding; the risk of HIV transmission to the infant can be significantly reduced with antiretroviral medications. (See 'Introduction'above.)
●Replacement feeding is recommended for infants born to HIV-infected mothers in the United States, which is the current standard of care in resource-rich settings. However, in developing countries, replacement feeding is associated with greater infant morbidity and mortality from diarrheal disease, pneumonia, and other infectious diseases. (See 'Replacement feeding' above.)
●The risk of HIV transmission through breast milk is greatest in the first several months of life; however, a lower but constant risk persists throughout the entire breastfeeding period. (See 'Timing of breast milk HIV transmission' above.)
●The risk of infant transmission increases with increased levels of maternal HIV RNA in plasma or breast milk. (See 'Cofactors for breast milk HIV transmission' above.)
●Antiretroviral medications significantly decrease the risk of mother-to-child transmission of HIV during the antepartum, intrapartum, and early postpartum periods. However, an excess risk of HIV transmission occurs if antiretroviral medications are discontinued during the breastfeeding period. Maternal and infant antiretroviral prophylaxis strategies during the breastfeeding period are comparably effective in reducing the rate of transmission, but antiretroviral therapy (ART) is now recommended for all HIV-infected individuals, including pregnant and breastfeeding women, and hence is the preferred strategy. (See 'Efficacy of antiretroviral drugs to prevent transmission during breastfeeding' above.)
●The World Health Organization recommends that ART be initiated in all pregnant and breastfeeding women, regardless of CD4 cell count, as soon as there is a risk of mother-to-child transmission of HIV in order to minimize this risk. A once-daily, fixed-dose combination of tenofovir, lamivudine (or emtricitabine), and efavirenz is the preferred first-line regimen. Lifelong continuation of ART is recommended. (See 'Maternal antiretroviral use' above.)
●Infant antiretroviral use remains important as postexposure prophylaxis after delivery and in settings in which maternal antiretroviral use is delayed or interrupted during breastfeeding (table 1 and algorithm 1). (See 'Infant antiretroviral use' above.)
●Exclusive breastfeeding, in combination with antiretroviral interventions, is recommended for the first six months of life as it leads to nutritional and immunologic benefits for the infant. Subsequently, breastfeeding, along with antiretroviral prophylaxis and appropriate complementary feeding, should continue for another six months given the increased infant morbidity associated with earlier weaning. (See 'Recommendations to prevent transmission during breastfeeding' above.)
Antiretroviral prophylaxis in infants born to HIV-infected mothers in resource-limited settings
This algorithm reflects the World Health Organization recommendations for infant antiretroviral prophylaxis to prevent mother-to-child transmission of HIV infection. Prophylaxis should start as soon as possible after birth, preferably within 6 to 12 hours. Refer to other UpToDate content for dosing details. In addition to infant prophylaxis, initiation of lifelong ART is recommended for all HIV-infected pregnant and breastfeeding women.
ART: antiretroviral therapy.
* If indicated, antiretroviral prophylaxis should be initiated prior to the availability of results of virologic testing. If the virologic test is positive, any prophylaxis regimen should be discontinued and the infant should start a combination ART regimen.
¶ If the mother interrupts ART during breastfeeding, the infant should be managed as indicated for an infant with HIV exposure identified more than 48 hours postpartum.
Δ If the mother cannot tolerate or declines ART, then the infant should continue nevirapine prophylaxis throughout the duration of breastfeeding, until one week following breastfeeding cessation (if nevirapine is not tolerated, daily lamivudine can be used).
◊ Uninfected infants who are using replacement feeding do not need antiretroviral prophylaxis because there is no ongoing risk of transmission through breast milk, and the period for effective prophylaxis of intrapartum transmission may be passed (ie, infant prophylaxis initiated 48 hours or more after birth is unlikely to affect intrapartum transmission).
* If indicated, antiretroviral prophylaxis should be initiated prior to the availability of results of virologic testing. If the virologic test is positive, any prophylaxis regimen should be discontinued and the infant should start a combination ART regimen.
¶ If the mother interrupts ART during breastfeeding, the infant should be managed as indicated for an infant with HIV exposure identified more than 48 hours postpartum.
Δ If the mother cannot tolerate or declines ART, then the infant should continue nevirapine prophylaxis throughout the duration of breastfeeding, until one week following breastfeeding cessation (if nevirapine is not tolerated, daily lamivudine can be used).
◊ Uninfected infants who are using replacement feeding do not need antiretroviral prophylaxis because there is no ongoing risk of transmission through breast milk, and the period for effective prophylaxis of intrapartum transmission may be passed (ie, infant prophylaxis initiated 48 hours or more after birth is unlikely to affect intrapartum transmission).
Reference:
- World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection Recommendations for a public health approach - Second edition. http://www.who.int/hiv/pub/arv/arv-2016/en/ (Accessed on July 8, 2016).
Graphic 108808 Version 2.0
Infant antiretroviral prophylaxis dosing
| Infant age | Dosing of nevirapine (NVP) | Dosing of zidovudine (AZT) |
| Birth to 6 weeks | ||
| Birth weight 2000 to 2499 grams* | 10 mg once daily (1 mL of syrup once daily) | 10 mg twice daily (1 mL of syrup twice daily) |
| Birth weight ≥2500 grams | 15 mg once daily (1.5 mL of syrup once daily) | 15 mg twice daily (1.5 mL of syrup twice daily) |
| >6 weeks to 12 weeks | ||
| 20 mg once daily (2 mL of syrup once daily or half a 50 mg tablet once daily) | 60 mg twice daily¶ (6 mL of syrup twice daily or a 60 mg tablet twice daily) | |
* For infants older than 35 weeks gestational age who weigh <2000 grams, the suggested doses are: NVP 2 mg/kg per dose once daily and AZT 4 mg/kg per dose twice daily. Premature infants younger than 35 weeks of gestational age should be dosed using expert guidance.
¶ The prophylaxis dose for zidovudine in these infants has not been established; the treatment dose is recommended.
¶ The prophylaxis dose for zidovudine in these infants has not been established; the treatment dose is recommended.
Reprinted from Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach - Second edition, World Health Organization, Annex 11, p. 388, Copyright © 2011. Available from: http://www.who.int/hiv/pub/arv/arv-2016/en/ (Accessed on June 21, 2016).
Graphic 108738 Version 1.0
Prevention of mother-to-child HIV transmission in resource-limited settings
New pediatric HIV infections from mother-to-child transmission remain a substantial health burden in resource-limited settings, particularly in sub-Saharan Africa. With improved access to antiretroviral agents and improved care delivery systems, international organizations have endorsed a goal of virtual elimination of perinatal transmission by 2015. (See 'Introduction' above and 'Burden of disease' above and 'Progress toward elimination'above.)
●Without preventive interventions, the risk of perinatal HIV transmission varies between 15 and 45 percent [9]. (See 'Risk of MTCT of HIV' above and 'Timing of HIV transmission from mothers to their infants' above and'Mechanisms of transmission' above.)
●The use of antiretroviral agents by pregnant women and their children is the most important intervention for prevention of mother-to-child transmission during antepartum, peripartum, and early postpartum periods. Nevertheless, successful prevention programs must also include other measures for optimal identification and long-term management of HIV-infected pregnant women. These include rapid HIV testing, monitoring and support for antiretroviral adherence and toxicity, counseling on infant feeding, effective family planning and reproductive health services, and linkage to long-term HIV care. (See 'Overview of care to prevent transmission'above.)
●Most clinicians in resource-limited settings will follow the World Health Organization (WHO) guidelines and the individual country’s national HIV program, which take into account not only efficacy but also programmatic feasibility and public health objectives. Various combinations of maternal and infant antiretroviral regimens have demonstrated efficacy in reducing the risk of perinatal HIV transmission. (See 'Efficacy of maternal antiretroviral use in prevention of in utero and intrapartum transmission' above and 'Efficacy of infant antiretroviral use in prevention of transmission' above.)
●The WHO recommends initiation of antiretroviral therapy (ART) for all HIV-infected pregnant or breastfeeding women, regardless of their CD4 cell count, as soon as pregnancy is recognized in an HIV-infected woman or HIV is diagnosed in a pregnant or breastfeeding woman. The fixed-dose combination of tenofovir, emtricitabine, and efavirenz is the preferred first-line regimen. ART should be continued lifelong. (See 'Maternal antiretroviral use' above.)
●The WHO recommends that all infants receive post-exposure prophylaxis to prevent transmission from exposure to HIV during delivery (and the early breastfeeding period, if applicable). The recommended regimen depends on the infant’s risk of infection, as determined by the timing of maternal infection and ART use, and the type of infant feeding (table 2 and algorithm 1). (See 'Infant antiretroviral use' above and "Prevention of HIV transmission during breastfeeding in resource-limited settings", section on 'Infant antiretroviral use'.)
●The use of antiretrovirals during pregnancy has generally been found safe in trials and experience to date, and the benefits for preventing transmission of a fatal illness outweigh the potential adverse reactions that may occur. However, data on the use of the preferred first-line regimen of efavirenz, tenofovir, and emtricitabine are limited, and concerns about adverse pregnancy outcomes, possible low risk of teratogenicity, and other fetal effects remain. Thus, continued monitoring for end-organ toxicities and birth defects HIV-infected pregnant women and their infants is necessary to assure both short-term and long-term safety. (See 'Adverse effects/safety'above and "Safety and dosing of antiretroviral medications in pregnancy".)
WHO clinical staging of HIV/AIDS for adults and adolescents with confirmed HIV infection
| Primary HIV infection |
| Asymptomatic |
| Acute retroviral syndrome |
| Clinical stage 1 |
| Asymptomatic |
| Persistent generalized lymphadenopathy (PGL) |
| Clinical stage 2 |
| Moderate unexplained weight loss (<10 percent of presumed or measured body weight) |
| Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis) |
| Herpes zoster |
| Angular cheilitis |
| Recurrent oral ulcerations |
| Papular pruritic eruptions |
| Seborrhoeic dermatitis |
| Fungal nail infections |
| Clinical stage 3 |
| Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations |
| Unexplained severe weight loss (>10 percent of presumed or measured body weight) |
| Unexplained chronic diarrhea for longer than one month |
| Unexplained persistent fever (above 37.6°C intermittent or constant for longer than one month) |
| Persistent oral candidiasis |
| Oral hairy leukoplakia |
| Pulmonary tuberculosis (current) |
| Severe bacterial infections (eg, pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteremia) |
| Acute necrotizing ulcerative stomatitis, gingivitis, or periodontitis |
| Conditions where confirmatory diagnostic testing is necessary |
| Unexplained anaemia (<8 g/dL), and/or neutropenia (<500 cells/microL), and/or chronic thrombocytopenia (<50,000/microL) for more than one month |
| Clinical stage 4* |
| Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations |
| HIV wasting syndrome |
| Pneumocystis pneumonia |
| Recurrent severe bacterial pneumonia |
| Chronic herpes simplex infection (orolabial, genital, or anorectal of more than one month's duration) |
| Esophageal candidiasis |
| Extrapulmonary tuberculosis |
| Kaposi's sarcoma |
| Central nervous system (CNS) toxoplasmosis |
| HIV encephalopathy |
| Conditions where confirmatory diagnostic testing is necessary |
| Extrapulmonary cryptococcosis, including meningitis |
| Disseminated non-tuberculous mycobacterial infection |
| Progressive multifocal leukoencephalopathy (PML) |
| Candida of trachea, bronchi, or lungs |
| Chronic cryptosporidiosis (with diarrhea) |
| Chronic isosporiasis |
| Visceral herpes simplex infection |
| Cytomegalovirus (CMV) infection (retinitis or infection of organs other than liver, spleen, or lymph nodes) |
| Disseminated mycosis (eg, histoplasmosis, coccidiomycosis) |
| Recurrent non-typhoidal salmonella bacteremia |
| Lymphoma (cerebral or B cell non-Hodgkin) or other solid HIV-associated tumors |
| Invasive cervical carcinoma |
| Atypical disseminated leishmaniasis |
| Symptomatic HIV-associated nephropathy or symptomatic HIV-associated cardiomyopathy |
* Some additional specific conditions can also be included in regional classifications (such as reactivation of American trypanosomiasis [meningitis and/or myocarditis] in the WHO region of the Americas, disseminated penicillinosis in Asia, and HIV-associated rectovaginal fistula in Africa).
Updated information from:
- WHO case definitions of HIV for surveillance and revised clinical staging and immunologic classification of HIV-related disease in adults and children. World Health Organization, Geneva, Switzerland, 2007. Available at: http://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf.
Graphic 55105 Version 3.0
Antiretroviral prophylaxis in infants born to HIV-infected mothers in resource-limited settings
This algorithm reflects the World Health Organization recommendations for infant antiretroviral prophylaxis to prevent mother-to-child transmission of HIV infection. Prophylaxis should start as soon as possible after birth, preferably within 6 to 12 hours. Refer to other UpToDate content for dosing details. In addition to infant prophylaxis, initiation of lifelong ART is recommended for all HIV-infected pregnant and breastfeeding women.
ART: antiretroviral therapy.
* If indicated, antiretroviral prophylaxis should be initiated prior to the availability of results of virologic testing. If the virologic test is positive, any prophylaxis regimen should be discontinued and the infant should start a combination ART regimen.
¶ If the mother interrupts ART during breastfeeding, the infant should be managed as indicated for an infant with HIV exposure identified more than 48 hours postpartum.
Δ If the mother cannot tolerate or declines ART, then the infant should continue nevirapine prophylaxis throughout the duration of breastfeeding, until one week following breastfeeding cessation (if nevirapine is not tolerated, daily lamivudine can be used).
◊ Uninfected infants who are using replacement feeding do not need antiretroviral prophylaxis because there is no ongoing risk of transmission through breast milk, and the period for effective prophylaxis of intrapartum transmission may be passed (ie, infant prophylaxis initiated 48 hours or more after birth is unlikely to affect intrapartum transmission).
* If indicated, antiretroviral prophylaxis should be initiated prior to the availability of results of virologic testing. If the virologic test is positive, any prophylaxis regimen should be discontinued and the infant should start a combination ART regimen.
¶ If the mother interrupts ART during breastfeeding, the infant should be managed as indicated for an infant with HIV exposure identified more than 48 hours postpartum.
Δ If the mother cannot tolerate or declines ART, then the infant should continue nevirapine prophylaxis throughout the duration of breastfeeding, until one week following breastfeeding cessation (if nevirapine is not tolerated, daily lamivudine can be used).
◊ Uninfected infants who are using replacement feeding do not need antiretroviral prophylaxis because there is no ongoing risk of transmission through breast milk, and the period for effective prophylaxis of intrapartum transmission may be passed (ie, infant prophylaxis initiated 48 hours or more after birth is unlikely to affect intrapartum transmission).
Reference:
- World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection Recommendations for a public health approach - Second edition. http://www.who.int/hiv/pub/arv/arv-2016/en/ (Accessed on July 8, 2016).
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Infant antiretroviral prophylaxis dosing
| Infant age | Dosing of nevirapine (NVP) | Dosing of zidovudine (AZT) |
| Birth to 6 weeks | ||
| Birth weight 2000 to 2499 grams* | 10 mg once daily (1 mL of syrup once daily) | 10 mg twice daily (1 mL of syrup twice daily) |
| Birth weight ≥2500 grams | 15 mg once daily (1.5 mL of syrup once daily) | 15 mg twice daily (1.5 mL of syrup twice daily) |
| >6 weeks to 12 weeks | ||
| 20 mg once daily (2 mL of syrup once daily or half a 50 mg tablet once daily) | 60 mg twice daily¶ (6 mL of syrup twice daily or a 60 mg tablet twice daily) | |
* For infants older than 35 weeks gestational age who weigh <2000 grams, the suggested doses are: NVP 2 mg/kg per dose once daily and AZT 4 mg/kg per dose twice daily. Premature infants younger than 35 weeks of gestational age should be dosed using expert guidance.
¶ The prophylaxis dose for zidovudine in these infants has not been established; the treatment dose is recommended.
¶ The prophylaxis dose for zidovudine in these infants has not been established; the treatment dose is recommended.
Reprinted from Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach - Second edition, World Health Organization, Annex 11, p. 388, Copyright © 2011. Available from: http://www.who.int/hiv/pub/arv/arv-2016/en/ (Accessed on June 21, 2016).
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