Skip Navigation LinksHome > April 1, 2005 - Volume 38 - Issue 4 > Trends in Antiretroviral Therapy Use and Survival Rates for...
JAIDS Journal of Acquired Immune Deficiency Syndromes:
Epidemiology and Social Science

Trends in Antiretroviral Therapy Use and Survival Rates for a Large Cohort of HIV-Infected Children and Adolescents in the United States, 1989-2001

McConnell, Michelle S MD*††; Byers, Robert H PhD†; Frederick, Toni PhD‡; Peters, Vicki B MD§; Dominguez, Kenneth L MD, MPH†; Sukalac, Thom†; Greenberg, Alan E MD, MPH†; Hsu, Ho-Wen MD∥; Rakusan, Tamara A MD¶‡‡; Ortiz, Idith R MD, MPH#; Melville, Sharon K MD**; Fowler, Mary Glenn MD, MPH†; for the Pediatric Spectrum of HIV Disease Consortium

Free Access
Article Outline
Collapse Box

Author Information

From the *Division of Applied Public Health Training, Centers for Disease Control and Prevention, Atlanta, GA; †Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA; ‡Los Angeles County Department of Health, Los Angeles, CA; §New York City Department of Health and Mental Hygiene, New York, NY; ∥State Laboratories Institute, Jamaica Plain, MA; ¶Children's National Medical Center, Washington, DC; #Puerto Rico Department of Health, San Juan, PR; **Texas Department of Health, Austin, TX; ††Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, GA; and ‡‡George Washington University School of Medicine, Washington, DC.

Received for publication February 3, 2004; accepted May 24, 2004.

Supported by the Division of HIV/AIDS, Centers for Disease Control and Prevention, under cooperative agreements U64/CCU303310, U64/CCU206818, U64/CCU114918, U64/CCU603300, U64/CCU903273, and U64/CCU202212.

A previous preliminary report of this study was made at the XIV International AIDS Conference, Barcelona, July 7-12, 2002.

Reprints: Michelle S. McConnell, Global AIDS Program, CDC 1600 Clifton Road, MS-E04, Atlanta, GA 30333 (e-mail: mmcconnell@cdc.gov).

Collapse Box

Abstract

Background: In the United States, HIV-infected children and adolescents are aging and using antiretroviral (ARV) therapy for extended periods of time.

Objective: To assess trends in ARV use and long-term survival in an observational cohort of HIV-infected children and adolescents in the United States.

Methods: The Pediatric Spectrum of HIV Disease Study (PSD) is a prospective chart review of more than 2000 HIV-infected children and adolescents. Patients were included in the analysis from enrollment until last follow-up.

Results: Triple-ARV therapy use (for 6 months or more) increased from 27% to 66% during 1997 to 2001 (P < 0.0001, χ2 for trend). The proportion of patients receiving 3 or more sequential triple-therapy regimens also increased from 4% to 17% during 1997 to 2001 (P < 0.0001, χ2 for trend), however, and the durability of triple-therapy regimens decreased from 13 to 7 months from the first to third regimen. Survival rates for the 1997 to 2001 birth cohorts were significantly better than for the 1989 to 1993 and 1994 to 1996 cohorts (P < 0.0001).

Conclusions: Survival rates in the PSD cohort have increased in association with triple-ARV therapy use. With continued changes in ARV regimens, effective modifications in ARV therapy and the sustainability of gains in survival need to be determined.

Since the mid-1990s, there has been a significant reduction in perinatal transmission of HIV in the United States1 as well as increased survival into adolescence and adulthood of the population of US children who were infected with HIV at birth or during childhood. Most of these children and adolescents have received long-term antiretroviral (ARV) therapy.2 Since the introduction of ARV therapy in the early 1990s, drug therapy guidelines have changed from suboptimal single- to dual- to potent triple-drug therapy, including protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs). The introduction of genotypic and phenotypic resistance testing has also allowed for modification of regimens to improve clinical outcomes.3 Reasons why clinicians change ARV regimens often depend on a variety of factors, including patient adherence, response to therapy, previous ARV use, and the presence of viral resistance.

Although the efficacy of combination ARV therapy in adults and children enrolled in clinical trials has been demonstrated, the prescribing patterns for ARVs and survival trends in observational cohort populations have been less well described. Furthermore, despite the association of highly active combination therapy and PIs with decreased mortality,4-8 studies of these regimens in adults have begun to address the question of whether the effects of sequential ARV regimens are less durable than the effects of the initial regimens,9 and the extent to which children and adolescents are receiving sequential combination ARV regimens has not yet been determined.

Herein, we describe patterns in ARV use and the association of these patterns with survival among HIV-infected children and adolescents enrolled in the Centers for Disease Control and Prevention's (CDC's) Pediatric Spectrum of HIV Disease Study (PSD). The PSD cohort includes children and adolescents who were all infected with HIV at a young age and follows them for much longer than do most clinical trials. The cohort also includes follow-up in both university tertiary care and community settings, which allows for greater generalization of results than does follow-up conducted exclusively at tertiary care settings.

Back to Top | Article Outline

METHODS

Pediatric Spectrum of Disease

The PSD is a longitudinal epidemiologic chart review study of HIV-exposed and HIV-infected children who were younger than 13 years of age at the time of enrollment. The PSD has collected data since 1989 on children and adolescents in 6 US geographic areas with some of the highest HIV prevalence rates: Puerto Rico, Texas, Massachusetts, Los Angeles County, New York City, and Washington, DC.10,11 The study has been approved by the institutional review boards at all participating sites.

Back to Top | Article Outline
Study Population and Data Collection

Participants in this analysis were all HIV-infected children or adolescents in the PSD and were included in the analysis until death or last follow-up. They were considered to be active in the cohort in a given year if they had data available for either of 2 6-month abstraction periods each year. Complete drug prescription data were available for participants who were active in the cohort from 1994 to 2001, and drug prescription data, excluding start and stop dates, were available for those participants active in the cohort before 1994. Data for the survival analysis were included for participants active in the cohort between 1989 and 2001.

Data were collected from HIV clinic charts and hospital records and included information on birth history, risk for HIV infection, date of initial HIV evaluation, laboratory confirmation of HIV diagnosis, presence of HIV-related signs and symptoms, history of AIDS-defining illnesses, hospitalizations, immunizations, age at death, type of medical reimbursement, and clinical trial participation. The CDC pediatric HIV classification system was used to define HIV infection status as well as clinical and immunologic categories.12 For the purpose of this report, we presume that ARV drugs prescribed were taken; ARV drugs were included in the analysis unless there was documentation that they were not taken. For drug prescriptions that had no start dates indicated, the start date was considered to be the date of the next chart abstraction during which a continuation of the drug was documented.

Back to Top | Article Outline
Antiretroviral Trends

We began ARV analyses in the PSD cohort as of 1994 because of the increased availability and use of ARVs beginning in that year, and trends in ARV prescription and sequential triple-therapy regimens were reported beginning in 1994. Trends in annual therapy use (monotherapy, dual-drug therapy, and triple-drug therapy) were assessed for children and adolescents who continued receiving these therapies for 6 months or more in a calendar year. The 6-month period was chosen to classify patients based on the predominant type of therapy in a given year. Patients with unclassified ARV use were those who changed between these 3 categories of drug regimens more frequently than every 6 months and thosewho died or were lost to follow-up during the 6-month period.

Back to Top | Article Outline
Trends in Sequential Triple Therapy

A change in a triple-therapy regimen was defined as a change in 2 or more drugs while continuing on at least a 3-drug regimen. To define a regimen change in accordance with the guidelines for use of antiretroviral agents in both children and adolescents, 2 drugs were chosen as necessary.3,13 Reasons for stopping drugs were not included in this definition because of limitations in chart documentation of this information and the high number of unknown reasons for drug changes.

Back to Top | Article Outline
Trends in Survival Rates

Survival rates were compared for children and adolescents in the following birth cohort groups: 1989 to 1993, 1994 to 1996, and 1997 to 2001. These years were chosen because they reflect sentinel time points in the announcement of pediatric clinical trial results or the availability of new ARV drugs licensed for pediatric use. In 1989, most children were not receiving ARV drugs; in 1994, most were receiving 1 or 2 ARV drugs; and by 1997, many children were receiving triple therapy with or without PIs. Survival analyses using Cox proportional hazard models were done to compare the survival rates of children based on birth cohort and use of triple-ARV therapy. Log rank tests were used to assess their differences.

For the survival analysis of those receiving triple-ARV therapy, all eligible children were included and categorized according to whether they had ever received triple-ARV therapy, and the analysis was adjusted for birth cohort. To address the potential bias of patients starting triple-ARV therapy because they had survived long enough for it to become available, an additional analysis was done for those patients who had ever received triple therapy, using time-varying covariates to account for time receiving therapy. This model was also adjusted for sex, race, site, and birth cohort. The adjusted hazard of death in this analysis was relative to that before starting triple therapy. The outcome measure for all survival analyses was age at time of death, and the null hypothesis was that survival times were equal for all 3 birth cohorts and for those ever or never receiving triple-ARV therapy.

Odds ratios (ORs), confidence intervals (CIs), and χ2 tests for trend were calculated using Epi-Info, version 6.0 (Centers for Disease Control and Prevention, Atlanta, GA). Kaplan Meier survival curves were calculated using SPSS (SPSS, Chicago, IL). Other data analyses were done with SAS, version 8.0 (SAS Institute, Cary, NC).

Back to Top | Article Outline

RESULTS

Study Populations

The number of children and adolescents included in the ARV analyses varied between 463 in 1989, 2196 in 1994, and 2040 in 2001. A minimum of 4% of participants in 2001 to a maximum of 10% of participants in 1989 were lost to follow-up. The birth cohort survival analysis had 1790 participants in the 1989 to 1993 birth cohorts, 643 in the 1994 to 1996 birth cohorts, and 331 in the 1997 to 2001 birth cohorts. The triple-therapy survival analysis had 1576 study participants who had received triple-ARV therapy and 1183 who had not.

Because of the decline in HIV-infected newborns in the United States,1 the PSD cohort represented, in large part, the same population of children and adolescents each year after 1994. The primary change in demographics from 1994 to 2001 was the median age of cohort participants, which increased from 4 years in 1994 to 9 years in 2001. Other changes in the cohort included an increasing proportion of African Ameri-cans and a greater proportion of children covered by Medicaid (Table 1). The mode of HIV infection remained primarily perinatal.

Table 1
Table 1
Image Tools

Assessment by birth cohort found earlier cohorts had a higher median age at initial HIV evaluation, with the median being 4.4 (interquartile range [IQR] = 19.3) months for the 1989 to 1993 birth cohort and 0.5 (IQR = 7.9) and 0.2 (IQR = 2.9) months for the 1994 to 1996 and 1997 to 2001 birth cohorts, respectively. There were also significant differences by race (P = 0.003) and site (P < 0.001). The overall groupings for race remained the same (6%-9% white, 53%-61% African American, and 33%-38% Hispanic), whereas the proportion in Massachusetts and New York decreased as the proportion in Texas increased. There were no differences by sex, and the proportion in later birth cohorts with non-perinatal transmission was too small for analysis.

Back to Top | Article Outline
Antiretroviral Therapy Use

In 1996, only 6% of children and adolescents in the PSD were taking 3 or more drugs, but in 2000 and 2001, 68% and 66% of patients, respectively, were prescribed triple therapy for at least 6 months per year (P < 0.0001, χ2 for trend; Fig. 1). In 2000 and 2001, 14% and 12% of patients, respectively, continued to receive dual therapy for more than 6 months of the year.

Figure 1
Figure 1
Image Tools

The characteristics of patients receiving different types of therapy for at least 6 months in 2001 were assessed. Differences by race/ethnicity included a significantly higher proportion of white and Hispanic patients (73% and 70%, respectively) receiving triple therapy compared with African-American patients (63%) (OR = 1.62 and OR = 1.36, 95% CI: 1.11-2.35 and 95 CI: 1.11-1.66, respectively). The racial differences, although trending in the same direction, were not significant in earlier years. For all patients in 2001, regardless of whether they were taking monotherapy, dual therapy, or triple therapy, the median viral load was less than 5000 copies/mL and all had a median CD4 count greater than 500 cells/mm3.

From 1994 through 2001, ARV therapy use also increased overall, with the greatest increase in the use of PIs. By 2001, 94% of patients were taking nucleoside reverse transcriptase inhibitors (NRTIs), 70% were taking PIs, and 35% were taking NNRTIs.

Back to Top | Article Outline
Trends in Sequential Triple-Therapy Regimens

Assessment of trends in sequential ARV regimens indicated that since 1997, increasing numbers of patients in the PSD cohort had received 3 or more triple-therapy regimens (P < 0.0001, χ2 for trend; Fig. 2). In 1997, 81% of patients receiving triple therapy were receiving their first regimen, 15% were receiving their second regimen, and 4% were receiving their third or greater regimen. In 2001, 56% of patients receiving triple therapy were receiving their first regimen; 27% were receiving their second regimen, and 17% were receiving their third or greater regimen. Furthermore, in 2001, 41 patients (3%) were receiving their fifth or greater triple-therapy regimen.

Figure 2
Figure 2
Image Tools

The durability of sequential triple-therapy regimens also decreased. The median duration of the first regimen was 13 months (IQR = 4-26 months), that of the second was 9 months (IQR = 3-21 months), and that of the third or greater was 7 months or less. Patients with a short duration of their first regimen (<1 year) were not significantly more likely to have a short duration of their second regimen.

In 2001, there were no significant differences in gender, mode of infection, clinical trial participation, or type of reimbursement between those who were receiving their third or greater triple-therapy regimen and those receiving their first or second regimen. Adolescents aged 13 years or older were significantly more likely to be receiving a third or greater triple-therapy regimen than were children aged 1 to 12 years (OR = 2.44, 95% CI: 1.84-3.25), however, and white patients were significantly more likely to be receiving their third or greater triple-therapy regimen than were African-American or Hispanic patients (OR = 1.64, 95% CI: 1.08-2.5).

The pattern of ARV drug use also differed for those patients receiving their third or greater regimen compared with those receiving any ARV regimen. Patients receiving their third or greater regimen in 2001 were at least twice as likely to use abacavir and lopinavir/ritonavir than were patients in the cohort as a whole (OR = 2.43 and OR = 3.07, 95% CI: 1.86-3.18 and 95% CI: 2.38-3.96, respectively). Patients receiving their third or greater triple-therapy regimen were also significantly more likely to receive amprenavir and efavirenz (OR = 1.64 and OR = 1.70, 95% CI: 1.19-2.26 and 95% CI: 1.29-2.24, respectively).

Back to Top | Article Outline
Survival Trends

Coincident with the increased prescription of triple therapy and PIs has been a significant improvement in survival rates in the 1997 to 2001 birth cohorts compared with earlier birth cohorts (P < 0.0001). Survival rates also improved between 1989 to 1993 and 1994 to 1996, but this difference was not statistically significant (Fig. 3).

Figure 3
Figure 3
Image Tools

Survival rates improved among those who received triple-ARV therapy for any length of time in contrast to those who never received triple therapy (P < 0.0001); this difference continued to be significant when birth cohort was included in the analysis (P = 0.006; see Fig. 3). Comparison of survival rates for those patients who had ever received triple-ARV therapy, adjusted for time taking the therapy, indicated that the hazard of death decreased with time receiving triple-ARV therapy. When adjusted for birth cohort, race, sex, and site, the 1994 to 1996 birth cohorts had significantly greater survival rates than the 1989 to 1993 birth cohorts (P < 0.05).

Back to Top | Article Outline

DISCUSSION

Triple-ARV therapy use and survival rates have increased among HIV-infected children and adolescents in the PSD cohort. The proportion of patients using newer ARV drugs and the proportion receiving their third or greater triple-ARV regimen have also increased between 1994 and 2001, however.

In accordance with guidelines to prescribe 3 ARV drugs initially, preferably including a PI or an NNRTI, most children in this observational cohort have been receiving triple therapy since 1999 and PIs since 1998. The finding that 12% of patients continued to receive dual-ARV therapy in 2001 can likely be attributed to the fact that these patients continue to have low viral loads and adequate immune function.

Although the proportion of children receiving triple therapy and PIs has remained relatively stable since 2000 and 1998, respectively, demand for new ARV drugs has continued. In particular, since 1998, there have been significant changes in the use of certain PIs and NNRTIs, such as lopinavir/ritonavir and efavirenz. Drugs such as T20 and tenofovir have also either recently been approved by the US Food and Drug Administration (T20) or are being studied in children (tenofovir) after being approved for use in adults.14 These and other new ARV drugs need to be tested further in pediatric and adolescent populations to determine the optimal ARV drug regimens for those who have already received a number of different ARV drugs.15-18

Coincident with the increased use of new ARV drugs are increasing numbers of patients who have received 3 or more triple-therapy regimens. Furthermore, the finding of decreasing duration of sequential triple-ARV regimens corroborates findings in the adult population.9 These trends pose new challenges for the treatment and care of HIV-infected children and adolescents and highlight the importance of determining the optimal treatment modifications for patients who do not respond to initial and sequential combination ARV therapy regimens.15

Nevertheless, survival rates of children and adolescents in the birth cohorts from 1997 to 2001 have improved since the introduction of triple-ARV therapy, and an improved survival rate is significantly associated with triple-ARV therapy use, even after adjustment for birth cohort. Furthermore, a Kaplan-Meier estimate of birth cohort survival found improved survival in both the 1989 to 1993 and 1994 to 1996 birth cohorts around 1998, when PIs and triple-ARV therapy became more common. Our findings support those of previous studies in the United States and Europe. An improved survival rate associated with triple-ARV therapy use was demonstrated in an observational cohort study of children perinatally infected with HIV-1, which was followed up through 1999 by de Martino and colleagues in Italy.5 The same finding was noted in a clinical trial population of pediatric patients followed up from 1996 through 1999 at tertiary care centers by the Pediatric AIDS Clinical Trials Group (PACTG).4 Given that our study had even longer follow-up times, we show that gains in survival rates have been sustained so far. Furthermore, the results of our analysis demonstrate overall longer survival in all cohort groups than did the study by de Martino et al.5,19 The trend toward improved survival rates and improved immune status of HIV-infected children and adolescents20 is likely influenced by increasing numbers of patients who were prescribed triple therapy as well as by improved HIV diagnostic technologies allowing for earlier diagnosis and the increasing prescription of prophylaxis for opportunistic infections. Early gains in survival in the 1994 to 1996 birth cohorts may be a result of these factors, which preceded the widespread introduction of triple-ARV therapy. Despite more patients receiving sequential triple-ARV regimens, the continued availability of new drugs may also be contributing to the sustainability of higher survival rates.

There are certain limitations to the PSD data and this analysis. In a prospective chart review, reasons for changes in ARV therapy (eg, potential ARV resistance, nonadherence, toxicity) are not always available; therefore, reasons for drug changes were not included in the analysis of changes in triple therapy. Clinician decisions about particular ARV regimens are based on laboratory values, history of adherence to ARV drugs, past ARV drug history, drug side effects, presence or absence of viral resistance, and clinical judgment. Although these factors do affect the trends in prescription of ARV drugs and survival rates reported here, the extent of each one's contribution could not be assessed. An additional limitation of the analysis is that it is often difficult to assess whether patients actually adhere to ARV therapy; although adherence can be inferred from medical chart data, charts more precisely convey prescribing patterns than actual ARV use. The findings presented here may also overestimate children receiving highly active antiretroviral therapy with either a PI or an NNRTI, but restriction of the definition of triple-ARV therapy would only strengthen the survival analysis findings. Lastly, the time period that patients were receiving a particular regimen may be underestimated because of missing start dates, which were noted in 10% of the 6-month chart abstractions.

In summary, these findings from the PSD cohort demonstrate that substantially more patients are receiving triple therapy and PIs than in earlier years and that survival rates have significantly improved for HIV-infected children since 1994. As the cohort of HIV-infected children and adolescents in the United States ages and continues to change regimens, however, demand for new ARV drugs continues. Further research is needed in the area of effective modifications of therapy and the role that ARV resistance and resistance monitoring plays in choosing optimal ARV regimens for those patients who have been taking them for a long time. As children and adolescents on ARV therapy go through hormonal changes and growth spurts associated with puberty, the late complications and toxicities of chronic exposure to highly active antiretroviral therapy also need to be carefully monitored and evaluated.

Back to Top | Article Outline

ACKNOWLEDGMENTS

The authors thank the following individuals: CDC: Kenneth Dominguez, Mary Glenn Fowler, Alan Greenberg, Beverly Bohannon, and Thom Sukalac; Massachusetts: Ho-Wen Hsu, Joyce Cohen, and Catherine Reddington (University of Massachusetts Medical School, State Laboratory Institute); Barbara Stechenberg, Eileen Theroux, and Maripat Toye (Baystate Medical Center-Springfield MA); Stephen Pelton, Anne Marie Regan, and Sam Theodore (Boston Medical Center); Kenneth McIntosh and Catherine Kneut (Boston Children's Hospital); Katherine Luzuriaga, Dorothy Smith, and Donna Picard (University of Massachusetts Medical School); Gerard Coste and Margaret Lynch (Cambridge Hospital); New York City: Vicki Peters, Kai-Li Liu, Polly Thomas, Chere Mapson, Annette Brooks, Myrna Beckles, Patricia Diggs, Stephanie Manning, Carol McFarlane, and Karla McFarlane (New York City Department of Health and Mental Hygiene); Arye Rubinstein (Albert Einstein Hospital); Saroj Bakshi (Bronx Lebanon Hospital); Edward Handelsman (Downstate University Hospital); Elaine Abrams (Harlem Hospital); Cathy Painter (Incarnation Children's Center); Andrew Wiznia (Jacobi Hospital); Ninad Desai (Kings County Medical Center); Nathan Litman (Montefiore Hospital); Joseph Stavola (New York Hospital); Jacob Abadi (North Central Bronx Hospital); Washington, DC: Tamara Rakusan, Hans Spiegel, Andrew Bonwit, Vonterris Hagan-Temple, and Waldo Perez (Children's National Medical Center); Sohail Rana, Renee Jenkins, Davene McCarthy-White, and Linda Hart (Howard University Hospital); Puerto Rico: Idith Ortiz, Juan Carlos Orengo, Aida Melendez, Myribel Santiago-Torres, Evelyn Rivera, Ruth Santos, and Emily Maldonado (Puerto Rico Departmento de Salud); Eleanor Jimenez and Luis A. Martinez (San Juan City Hospital); Irma Febo and Lissette Lugo (University Pediatric Hospital); Wanda Figueroa and Odette Garcia (Bayamon Regional Hospital); Jose Vazquez Julia (Caguas Regional Hospital); Rosa Delgado, Ortando Quincoce, and Judith Gautier (Ponce Regional Hospital); Texas: Sharon Melville, Richard Yeager, and Mary James (Texas Department of Health); Octavio Ramilo and Janeen Graper (Children's Hospital-Dallas); Terence Doran, Rachel Davis, and Mary Jane Varela (University of Texas-San Antonio); Gilberto Handel and Tony Millon (Texas Tech Medical Center-El Paso); Gloria Heresi and Kathleen Paul (University of Texas-Houston); Mary Paul and Amy Leonard (Baylor College of Medicine-Houston); Janak Patel and Andrea Smith (University of Texas Medical Branch-Galveston); Saramistha Hauger, MariFran Shannon, and Nelda Garcia (Children's Hospital of Austin); Los Angeles County: Toni Frederick, Laurene Mascola, Yon Silvia Walker, Janielle Jackson-Alvarez, and Priya Mukhopadhyay (Los Angeles County Department of Health); Yvonne Bryson (UCLA School of Medicine); Joseph Church (Children's Hospital of Los Angeles); Audra Deveikis (Memorial Miller Children's Hospital); Margaret Keller (Harbor-UCLA Medical Center); Deborah Lehman (Cedars-Sinai Medical Center); Andrea Kovacs (LAC and USC Maternal Child Clinic); Steve Taylor (Martin Luther King, Jr/Drew Medical Center); Victor K. Wong (Southern California Kaiser Permanente).

Back to Top | Article Outline

REFERENCES

1. Lindegren ML, Byers RH, Thomas P, et al. Trends in perinatal transmission of HIV/AIDS in the United States. JAMA. 1999;282:531-538.

2. Abrams E, Weedon J, Bertolli J, et al. Aging cohort of perinatally human immunodeficiency virus-infected children in New York City. Pediatr Infect Dis J. 2001;20:511-517.

3. National Institutes of Health. Guidelines for the use of antiretroviral agents in pediatric HIV infection-June 25, 2003. Available at: http://www.aidsinfo.nih.gov/guidelines/. Accessed August 8, 2003.

4. Gortmaker SL, Hughes M, Cervia J, et al. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med. 2001;345:1522-1528.

5. de Martino M, Tovo P-A, Balducci M, et al. Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. JAMA. 2000;284:190-197.

6. Pallela FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338:853-860.

7. Lee LM, Karon JM, Selik R, et al. Survival after AIDS diagnosis in adolescents and adults during the treatment era, United States, 1984-1997. JAMA. 2001;285:1308-1315.

8. Moore R, Chaisson R. Natural history of HIV infection in the era of combination antiretroviral therapy. AIDS. 1999;13:1933-1942.

9. Palella FJ, Chmiel JS, Moorman AC, et al. Durability and predictors of success of highly active antiretroviral therapy (HAART) for ambulatory HIV-infected patients. AIDS. 2002;16:1617-1626.

10. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. 1994;6:1-39.

11. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. 2001;13:1-44.

12. Centers for Disease Control and Prevention. 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Morb Mortal Wkly Rep. 1994;43:1-10.

13. National Institutes of Health. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents-July 14, 2003. Available at: http://www.aidsinfo.nih.gov/guidelines/. Accessed August 8, 2003.

14. National Institutes of Health. Drugs. Available at: http://www.aidsinfo.nih.gov/. Accessed May 8, 2003.

15. Weidle P, Lichtenstein KA, Moorman AC, et al. Factors associated with the successful modification of antiretroviral therapy. AIDS. 2000;14:491-497.

16. Stephenson J. New class of anti-HIV drugs. JAMA. 1999;282:1994.

17. De Clerq E. New anti-HIV agents and targets. Med Res Rev. 2002;22:531-565.

18. Riera M, Ribas MA, Perez Elias MJ, et al. Approach to treatment of patients with virologic failure to multiple regimens. Enferm Infecc Microbiol Clin. 2002;20(Suppl 2):58-67.

19. Teglas J, Mayaux M, Blanche S, et al. Antiretroviral therapy and mortality among children with perinatal HIV infection. JAMA. 2000;284:2871-2872.

20. Frederick T, Mascola L, Peters V, et al. Trends in HAART use and immune status among HIV-infected infants and children in the Pediatric Spectrum of Disease project, United States, 1994-2000 [abstract TuPeC4735]. In: Programs and Abstracts of the XIV International Conference on AIDS. Barcelona, July 7-12, 2002.

Cited By:

This article has been cited 40 time(s).

Samj South African Medical Journal
Antiretroviral treatment for children
Eley, B; Davies, MA; Apolles, P; Cowburn, C; Buys, H; Zampoli, M; Finlayson, H; King, S; Nuttall, J
Samj South African Medical Journal, 96(9): 988-993.

American Journal of Obstetrics and Gynecology
Young, seropositive, and pregnant: epidemiologic and psychosocial perspectives on pregnant adolescents with human immunodeficiency virus infection
Koenig, LJ; Espinoza, L; Hodge, K; Ruffo, N
American Journal of Obstetrics and Gynecology, 197(3): S123-S131.
10.1016/j.ajog.2007.03.004
CrossRef
Journal of Antimicrobial Chemotherapy
Trends in the prescription of antiretroviral drugs and impact on plasma HIV-RNA measurements
Jimenez-Nacher, I; Garcia, B; Barreiro, P; Rodriguez-Novoa, S; Morello, J; Gonzalez-Lahoz, J; de Mendoza, C; Soriano, V
Journal of Antimicrobial Chemotherapy, 62(4): 816-822.
10.1093/jac/dkn252
CrossRef
Clinical Infectious Diseases
Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association of the Infectious Diseases Society of America
Aberg, JA; Kaplan, JE; Libman, H; Emmanuel, P; Anderson, JR; Stone, VE; Oleske, JM; Currier, JS; Gallant, JE
Clinical Infectious Diseases, 49(5): 651-681.
10.1086/605292
CrossRef
AIDS Research and Human Retroviruses
Impact of Highly Active Antiretroviral Therapy (HAART) on AIDS and Death in a Cohort of Vertically HIV Type 1-Infected Children: 1980-2006
Palladino, C; Bellon, JM; Jarrin, I; Gurbindo, MD; De Jose, MI; Ramos, JT; Gonzalez-Iome, MI; Mellado, MJ; Beceiro, J; Del Amo, J; Munoz-Fernandez, MA
AIDS Research and Human Retroviruses, 25(): 1091-1097.
10.1089/aid.2009.0070
CrossRef
Mental Retardation and Developmental Disabilities Research Reviews
Neurodevelopment and chronic illness: Mechanisms of disease and treatment
Armstrong, FD
Mental Retardation and Developmental Disabilities Research Reviews, 12(3): 168-173.
10.1002/mrdd.20114
CrossRef
Indian Pediatrics
Management Issues among Children Living with HIV: Looking Ahead
Shet, A; Kumarasamy, N
Indian Pediatrics, 45(): 955-960.

Antiviral Therapy
Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina
Vignoles, M; Barboni, G; Agosti, MR; Quarleri, J; Garcia, MK; Ayala, SG; Salomon, H
Antiviral Therapy, 14(8): 1175-1181.
10.3851/IMP1461
CrossRef
Journal of Adolescent Health
Epidemiology of HIV and AIDS among adolescents and young adults in the United States
Rangel, MC; Gavin, L; Reed, C; Fowler, MG; Lee, LM
Journal of Adolescent Health, 39(2): 156-163.
10.1016/j.jadohealth.2006.02.011
CrossRef
Tropical Medicine & International Health
Vertically acquired paediatric HIV infection: the challenges of providing comprehensive packages of care in resource-limited settings
Little, KE; Bland, RM; Newell, ML
Tropical Medicine & International Health, 13(9): 1098-1110.
10.1111/j.1365-3156.2008.02130.x
CrossRef
Pediatrics
Increasing antiretroviral drug access for children with HIV infection
Swan, J; Lyall, H; Moreau, E; Wilfert, C; Shah, N; Grange, A; Bissot, A; Giaquinto, C; Christie, CDC; Phillips, C; Thisyakorn, U; Lallemant, M; Sharland, M; Bobat, R; Cotton, M; Venter, F; Cooper, P; Crowley, S
Pediatrics, 119(4): 838-845.
10.1542/peds.2007-0273
CrossRef
Journal of Infectious Diseases
Challenges to pediatric HIV care and treatment in South Africa
Meyers, T; Moultrie, H; Naidoo, K; Cotton, M; Eley, B; Sherman, G
Journal of Infectious Diseases, 196(): S474-S481.
10.1086/521116
CrossRef
Journal of Applied Developmental Psychology
Standing between two worlds in Harlem: A developmental psychopathology perspective of perinatally acquired human immunodeficiency virus and adolescence
Kang, E; Mellins, CA; Ng, WYK; Robinson, LG; Abrams, EJ
Journal of Applied Developmental Psychology, 29(3): 227-237.
10.1016/j.appdev.2008.02.001
CrossRef
Journal of Urban Health-Bulletin of the New York Academy of Medicine
HIV Testing Rates, Testing Locations, and Healthcare Utilization among Urban African-American Men
Petroll, AE; DiFranceisco, W; McAuliffe, TL; Seal, DW; Kelly, JA; Pinkerton, SD
Journal of Urban Health-Bulletin of the New York Academy of Medicine, 86(1): 119-131.
10.1007/s11524-008-9339-y
CrossRef
Pediatrics
Trends in hospitalizations of HIV-infected children and adolescents in the United States: Analysis of data from the 1994-2003 nationwide inpatient sample
Kourtis, AP; Bansil, P; Posner, SF; Johnson, C; Jamieson, DJ
Pediatrics, 120(2): E236-E243.
10.1542/peds.2006-3268
CrossRef
Clinical Infectious Diseases
Long-term effectiveness of highly active Antiretroviral therapy on the survival of children and adolescents with HIV infection: A 10-year follow-up study
Patel, K; Hernan, MA; Williams, PL; Seeger, JD; McIntosh, K; Van Dyke, RB; Seage, GR
Clinical Infectious Diseases, 46(4): 507-515.
10.1086/526524
CrossRef
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/Hiv
Pregnancy care in two adolescents perinatally infected with HIV
Meloni, A; Tuveri, M; Floridia, M; Zucca, F; Borghero, G; Gariel, D; Melis, GB
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/Hiv, 21(6): 796-798.
10.1080/09540120802511976
CrossRef
Expert Opinion on Pharmacotherapy
Recommendations in pediatric antiretroviral therapy
Ikeda, T; Ch'ng, TW; Oleske, JM
Expert Opinion on Pharmacotherapy, 8(2): 155-166.
10.1517/146565660.8.2.155
CrossRef
Jama-Journal of the American Medical Association
Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia
Bolton-Moore, C; Mubiana-Mbewe, M; Cantrell, RA; Chintu, N; Stringer, EM; Chi, BH; Sinkala, M; Kankasa, C; Wilson, CM; Wilfert, CM; Mwango, A; Levy, J; Abrams, EJ; Bulterys, M; Stringer, JSA
Jama-Journal of the American Medical Association, 298(): 1888-1899.

Journal of Tropical Pediatrics
Efficacy of Antiretroviral Therapy Program in Children in India: Prognostic Factors and Survival Analysis
Rajasekaran, S; Jeyaseelan, L; Ravichandran, N; Gomathi, C; Thara, F; Chandrasekar, C
Journal of Tropical Pediatrics, 55(4): 225-232.
10.1093/tropej/fmm073
CrossRef
Annals of Internal Medicine
The changing face of HIV care: Common things really are common
Aberg, JA
Annals of Internal Medicine, 145(6): 463-465.

Pediatrics
Adherence to antiretroviral therapy for pediatric HIV infection: A qualitative systematic review with recommendations for research and clinical management
Simoni, JM; Montgomery, A; Martin, E; New, M; Demas, PA; Rana, S
Pediatrics, 119(6): E1371-E1383.
10.1542/peds.2006-1232
CrossRef
Asian Biomedicine
Clinical manifestations and survival of children with perinatal HIV-infection in Northeast Thailand
Lumbiganon, D; Lumbiganon, P; Kosalaraksa, P; Loapaiboon, M
Asian Biomedicine, 3(2): 143-150.

Sao Paulo Medical Journal
Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy
Gil, AC; Lorenzetti, R; Mendes, GB; Morcillo, AM; Toro, AADC; do Silva, MTN; Vilela, MMD
Sao Paulo Medical Journal, 125(4): 205-209.

International Journal of Std & AIDS
Factors associated with lack of antiretroviral adherence among adolescents in a reference centre in Rio de Janeiro, Brazil
Filho, LFB; Nogueira, SA; Machado, ES; Abreu, TF; de Oliveira, RH; Evangelista, L; Hofer, CB
International Journal of Std & AIDS, 19(): 685-688.
10.1258/ijsa.2008.008017
CrossRef
Journal of Pediatric Psychology
Psychological adjustment in children and families living with HIV
New, MJ; Lee, SS; Elliott, BM
Journal of Pediatric Psychology, 32(2): 123-131.
10.1093/jpepsy/jsj121
CrossRef
Annual Review of Medicine
Growing Up with HIV: Children, Adolescents, and Young Adults with Perinatally Acquired HIV Infection
Hazra, R; Siberry, GK; Mofenson, LM
Annual Review of Medicine, 61(): 169-185.
10.1146/annurev.med.050108.151127
CrossRef
Indian Journal of Dermatology Venereology & Leprology
Use of anti-retrovirals in pediatric HIV infection
Gaur, S
Indian Journal of Dermatology Venereology & Leprology, 74(3): 208-214.

AIDS
Early antiretroviral therapy of HIV-infected infants in resource-limited countries: possible, feasible, effective and challenging
Becquet, R; Mofenson, LA
AIDS, 22(): 1365-1368.

AIDS Patient Care and Stds
Family experiences with pediatric antiretroviral therapy: Responsibilities, barriers, and strategies for remembering medications
Marhefka, SL; Koenig, LJ; Allison, S; Bachanas, P; Bulterys, M; Bettica, L; Tepper, VJ; Abrams, EJ
AIDS Patient Care and Stds, 22(8): 637-647.
10.1089/apc.2007.0110
CrossRef
AIDS
Costs and benefits of HAART for patients with HIV in a public hospital in Mexico
Aracena-Genao, B; Navarro, JO; Lamadrid-Figueroa, H; Forsythe, S; Trejo-Valdivia, B
AIDS, 22(): S141-S148.

Revista Brasileira De Medicina DO Esporte
Immunological and Virological Characteristics and Performance in the Variables Flexibility and Abdominal Resistence Strength of Hiv/AIDS Adolescents Under Highly Active Antirretroviral Therapy
dos Santos, FF; Pereira, FB; da Silva, CLO; Lazzarotto, AR; Petersen, RDD
Revista Brasileira De Medicina DO Esporte, 19(1): 40-43.

Journal of Musculoskeletal & Neuronal Interactions
Bone geometry and strength are adapted to muscle force in children and adolescents perinatally infected with HIV
Macdonald, HM; Chu, J; Nettlefold, L; Maan, EJ; Forbes, JC; Coto, H; Alimenti, A
Journal of Musculoskeletal & Neuronal Interactions, 13(1): 53-65.

Infection
Italian consensus statement on paediatric HIV infection
Giaquinto, C; Penazzato, M; Rosso, R; Bernardi, S; Rampon, O; Nasta, P; Ammassari, A; Antinori, A; Badolato, R; Gattinara, GC; Monforte, AD; De Martino, M; De Rossi, A; Di Gregorio, P; Esposito, S; Fatuzzo, F; Fiore, S; Franco, A; Gabiano, C; Galli, L; Genovese, O; Giacomet, V; Giannattasio, A; Gotta, C; Guarino, A; Martino, A; Mazzotta, F; Principi, N; Regazzi, MB; Rossi, P; Russo, R; Saitta, M; Salvini, F; Trotta, S; Vigano, A; Zuccotti, G; Carosi, G
Infection, 38(4): 301-319.
10.1007/s15010-010-0020-5
CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Declines in Mortality Rates and Changes in Causes of Death in HIV-1-Infected Children During the HAART Era
Brady, MT; Oleske, JM; Williams, PL; Elgie, C; Mofenson, LM; Dankner, WM; Van Dyke, RB; for the Pediatric AIDS Clinical Trials Group219/219C Team,
JAIDS Journal of Acquired Immune Deficiency Syndromes, 53(1): 86-94.
10.1097/QAI.0b013e3181b9869f
PDF (295) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
National Program Scale-Up and Patient Outcomes in a Pediatric Antiretroviral Treatment Program, Thailand, 2000-2007
McConnell, MS; Chasombat, S; Siangphoe, U; Yuktanont, P; Lolekha, R; Pattarapayoon, N; Kohreanudom, S; Mock, PA; Fox, K; Thanprasertsuk, S
JAIDS Journal of Acquired Immune Deficiency Syndromes, 54(4): 423-429.
10.1097/QAI.0b013e3181dc5eb0
PDF (203) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Trends in Pregnancy-Related and Delivery Hospitalizations Among HIV-Infected Adolescents, 1994 to 2004
Bansil, P; Jamieson, DJ; Posner, SF; Johnson, CH; Kourtis, AP
JAIDS Journal of Acquired Immune Deficiency Syndromes, 46(4): 514-515.
10.1097/QAI.0b013e31815b2d7f
PDF (277) | CrossRef
The Journal of Nervous and Mental Disease
Psychiatric Diagnosis and Antiretroviral Adherence Among Adolescent Medicaid Beneficiaries Diagnosed With Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome
Walkup, J; Akincigil, A; Bilder, S; Rosato, NS; Crystal, S
The Journal of Nervous and Mental Disease, 197(5): 354-361.
10.1097/NMD.0b013e3181a208af
PDF (301) | CrossRef
The Pediatric Infectious Disease Journal
Antiretroviral Therapy in HIV-Infected Infants and Children
Marón, G; Gaur, AH; Flynn, PM
The Pediatric Infectious Disease Journal, 29(4): 360-363.
10.1097/INF.0b013e3181d616d8
PDF (176) | CrossRef
The Pediatric Infectious Disease Journal
Hospitalization Trends Among Children and Youths With Perinatal Human Immunodeficiency Virus Infection, 1990–2002
Melville, SK; Dominguez, K; for the Pediatric Spectrum of HIV Disease Study, ; Bertolli, J; Hsu, H; Sukalac, T; Williamson, J; Peters, V; Frederick, T; Rakusan, TA; Ortiz, I
The Pediatric Infectious Disease Journal, 25(7): 628-633.
10.1097/01.inf.0000220255.14636.b3
PDF (626) | CrossRef
Back to Top | Article Outline
Keywords:

pediatric HIV; survival trends; antiretroviral therapy; durability of therapy

© 2005 Lippincott Williams & Wilkins, Inc.

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.