Pharmacokinetics, safety and efficacy of maraviroc in treatment-experienced pediatric patients Infected with CCR5-tropic HIV-1

BACKGROUND: Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat adults infected with CC-chemokine receptor 5-tropic (R5) HIV-1. Study A4001031 was conducted to evaluate the pharmacokinetics, safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced pediatric patients infected with R5 HIV-1 and support registration of maraviroc for pediatric use. METHODS: This is an open-label, 2-stage, age-stratified, noncomparative multicenter study. One-hundred and three participants were enrolled into 4 age/formulation cohorts and dosed twice daily. Initial doses were determined by body surface area and optimized background therapy, based on drug interactions with maraviroc in adults. Dose adjustment and pharmacokinetic reevaluation occurred if the average concentrations (Cavg) at Week 2 were <100 ng/mL (Stage 1-dose finding). RESULTS: Data from the Week 48 analysis demonstrated that 49/50 Stage 1 participants rolling over into Stage 2 (safety and efficacy) achieved Cavg ≥100 ng/mL. Doses were identified that achieved similar concentration ranges to those seen in adults. The majority (90/103) received optimized background therapy containing potent cytochrome P450 3A inhibitors. Maraviroc was well tolerated and the safety and efficacy were comparable to those of adults. All cohorts had a mean decrease from baseline in HIV-1 RNA of >1 log10. Increases from baseline in the median CD4+ cell count and percentage were seen for all age groups. CONCLUSIONS: The maraviroc dosing strategy resulted in participants achieving the target Cavg, with exposure ranges similar to those observed in adults on approved doses. The safety and efficacy of maraviroc in this pediatric population were comparable to those seen in adults

Ceftriaxone versus ceftriaxone plus a macrolide for community-acquired pneumonia in hospitalized patients with HIV/AIDS: a randomized controlled trial

OBJECTIVES: To evaluate if treatment with ceftriaxone and a macrolide, improved patient outcome when compared with monotherapy with ceftriaxone, in hospitalized patients with human immunodeficiency virus/acquired immunodeficient syndrome (HIV/AIDS) with community-acquired pneumonia (CAP). METHODS: Adult patients with HIV hospitalized due to suspected CAP were randomized to receive one of two regimens, ceftriaxone plus macrolide or ceftriaxone plus placebo, at a 1:1 proportion (Brazilian Clinical Trials Registry: RBR-8wtq2b). The primary outcome was in-hospital mortality and the secondary outcomes were mortality within 14 days, need for vasoactive drugs, need for mechanical ventilation, time to clinical stability and length of hospitalization. RESULTS: A total of 227 patients were randomized, two were excluded after randomization; 225 patients were analysed (112 receiving ceftriaxone plus placebo and 113 receiving ceftriaxone plus macrolide). The frequency of the primary outcome, in-hospital mortality, was not statistically different between the regimens: 12/112 (11%) patients who received ceftriaxone plus placebo and 17/113 (15%) who received ceftriaxone plus macrolide died during hospitalization (hazard ratio 1.22, 95% CI 0.57-2.59). We did not find differences between the regimens for any of the secondary outcomes, including mortality within 14 days, which occurred in 5/112 (4%) patients with ceftriaxone plus placebo and in 12/113 (11%) patients with ceftriaxone plus macrolide (relative risk 2.38, 95% CI 0.87-6.53) CONCLUSIONS: Among hospitalized patients with HIV/AIDS with CAP, treatment with ceftriaxone and a macrolide did not improve patient outcomes, when compared with ceftriaxone monotherapy

Costs and benefits of secrecy: the dilemma experienced by adolescents seropositive for HIV

This study explored the experiences of the first generation of adolescents who acquired HIV through vertical transmission when disclosing their diagnosis to friends and romantic partners. The study sample was selected by convenience, with 20 patients (13-20 years old) participating in a qualitative investigation using individual interviews (language: Portuguese; duration: 45 minutes). The participants were followed in specialized clinics for the treatment of pediatric AIDS in São Paulo, Brazil. The results suggest that families who live with HIV tend to keep it a secret, and such behavior is learned and accepted unquestioningly as natural. Respect for privacy and the fear of rejection, coupled with the belief that information about their disease will be spread, are the main beliefs with which participants justify their secrecy. In terms of romantic relationships, adolescents were aware that their HIV status should at some point be shared with current or future sexual partners. However, the decision to reveal an HIV diagnosis in romantic relationships is permeated by anxieties, uncertainties about the right time, and fear of abandonment. In any case, telling the truth requires trust, guarantees of the other's love, and, in some cases, probing romantic partners beforehand to learn their perceptions about the disease. Participants who had experiences disclosing their HIV status shared positive and negative results, including emotional support, acceptance, and understanding, along with ostracism, discrimination, and abandonment by family members. The findings of this paper reinforce the challenges of revealing an HIV diagnosis to third parties. It requires understanding the meaning and importance of the secret for each patient, along with the conflict between the right to confidentiality and the responsibility of treating others exposed to the disease. All these aspects should be discussed extensively with this population and incorporated into clinical practice

Prospective etiological investigation of community-acquired pulmonary infections in hospitalized people living with HIV

The study of the etiological agents of community-acquired pulmonary infections is important to guide empirical therapy, requires constant updating, and has a substantial impact on the prognosis of patients. The objective of this study is to determine prospectively the etiology of community-acquired pulmonary infections in hospitalized adults living with HIV. Patients were submitted to an extended microbiological investigation that included molecular methods. The microbiological findings were evaluated according to severity of the disease and pneumococcal vaccine status. Two hundred twenty-four patients underwent the extended microbiological investigation of whom 143 (64%) had an etiology determined. Among the 143 patients with a determined etiology, Pneumocystis jirovecii was the main agent, detected in 52 (36%) cases and followed by Mycobacterium tuberculosis accounting for 28 (20%) cases. Streptococcus pneumoniae and Rhinovirus were diagnosed in 22 (15%) cases each and influenza in 15 (10%) cases. Among atypical bacteria, Mycoplasma pneumoniae was responsible for 12 (8%) and Chlamydophila pneumoniae for 7 (5%) cases. Mixed infections occurred in 48 cases (34%). S pneumoniae was associated with higher severity scores and not associated with vaccine status. By using extended diagnostics, a microbiological agent could be determined in the majority of patients living with HIV affected by community-acquired pulmonary infections. Our findings can guide clinicians in the choice of empirical therapy for hospitalized pulmonary disease

Costs and benefits of secrecy: the dilemma experienced by adolescents seropositive for HIV.

This study explored the experiences of the first generation of adolescents who acquired HIV through vertical transmission when disclosing their diagnosis to friends and romantic partners. The study sample was selected by convenience, with 20 patients (13-20 years old) participating in a qualitative investigation using individual interviews (language: Portuguese; duration: 45 minutes). The participants were followed in specialized clinics for the treatment of pediatric AIDS in São Paulo, Brazil. The results suggest that families who live with HIV tend to keep it a secret, and such behavior is learned and accepted unquestioningly as natural. Respect for privacy and the fear of rejection, coupled with the belief that information about their disease will be spread, are the main beliefs with which participants justify their secrecy. In terms of romantic relationships, adolescents were aware that their HIV status should at some point be shared with current or future sexual partners. However, the decision to reveal an HIV diagnosis in romantic relationships is permeated by anxieties, uncertainties about the right time, and fear of abandonment. In any case, telling the truth requires trust, guarantees of the other's love, and, in some cases, probing romantic partners beforehand to learn their perceptions about the disease. Participants who had experiences disclosing their HIV status shared positive and negative results, including emotional support, acceptance, and understanding, along with ostracism, discrimination, and abandonment by family members. The findings of this paper reinforce the challenges of revealing an HIV diagnosis to third parties. It requires understanding the meaning and importance of the secret for each patient, along with the conflict between the right to confidentiality and the responsibility of treating others exposed to the disease. All these aspects should be discussed extensively with this population and incorporated into clinical practice.

HIV-1 drug resistance and second-line treatment in children randomized to switch at low versus higher RNA thresholds

BACKGROUND: The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold. METHODS: PENPACT-1 had a 2 × 2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, and switch at a 1000 copies/mL versus 30,000 copies/mL threshold. Switch criteria were not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or Center for Disease Control and Prevention stage C event. Resistance tests were performed on samples ≥1000 copies/mL before switch, resuppression, and at 4-years/trial end. RESULTS: Sixty-seven children started PI-based ART and were randomized to switch at 1000 copies/mL (PI-1000), 64 PIs and 30,000 copies/mL (PI-30,000), 67 NNRTIs and 1000 copies/mL (NNRTI-1000), and 65 NNRTI and 30,000 copies/mL (NNRTI-30,000). Ninety-four (36%) children reached the 1000 copies/mL switch criteria during 5-year follow-up. In 30,000 copies/mL threshold arms, median time from 1000 to 30,000 copies/mL switch criteria was 58 (PI) versus 80 (NNRTI) weeks (P = 0.81). In NNRTI-30,000, more nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000 copies/mL (23% NNRTI-1000, 27% NNRTI-30,000). Sixty-two children started abacavir + lamivudine, 166 lamivudine + zidovudine or stavudine, and 35 other NRTIs. The abacavir + lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30,000, 64% NNRTI-1000, and 100% NNRTI-30,000 were <400 copies/mL 24 weeks later. CONCLUSIONS: Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line. An abacavir + lamivudine NRTI combination seemed protective against development of NRTI resistance

Long-term efficacy and safety of tenofovir disoproxil fumarate in HIV-1-infected adolescents failing antiretroviral therapy: the final results of study GS-US-104-0321.

BACKGROUND: Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321). METHODS: HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients. RESULTS: Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline. CONCLUSIONS: Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.

CD18 deficiency evolving to megakaryocytic (M7) acute myeloid leukemia: case report.

Leukocyte adhesion deficiency type 1 (LAD 1 - CD18 deficiency) is a rare disease characterized by disturbance of phagocyte function associated with less severe cellular and humoral dysfunction. The main features are bacterial and fungal infections predominantly in the skin and mucosal surfaces, impaired wound healing and delayed umbilical cord separation. The infections are indolent, necrotic and recurrent. In contrast to the striking difficulties in defense against bacterial and fungal microorganisms, LAD 1 patients do not exhibit susceptibility to viral infections and neoplasias. The severity of clinical manifestations is directly related to the degree of CD18 deficiency. Here, a 20 year-old female presenting a partial CD18 deficiency that developed a megakaryocytic (M7) acute myeloid leukemia is described for the first time. The clinical features of the patient included relapsing oral thrush due to Candida, cutaneous infections and upper and lower respiratory tract infections, followed by a locally severe necrotic genital herpetic lesion. The patient's clinical features improved for a period of approximately two years, followed by severe bacterial infections. At that time, the investigation showed a megakaryocytic acute myeloid leukemia, treated with MEC without clinical improvement. The highly aggressive evolution of the leukemia in this patient suggests that adhesion molecules could be involved in the protection against the spread of neoplastic cells.

Efficacy and safety of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents: 5 years of experience.

BACKGROUND: To evaluate the long-term (up to week 292) safety, efficacy and tolerability of ritonavir-boosted tipranavir in HIV-1-infected pediatric patients. Long-term follow up of patients enrolled in the randomized, open-label pediatric trial (1182.14/PACTG1051). METHODS: HIV-1-infected pediatric patients (2-18 years) who participated in the PACTG 1051 trial were followed for ritonavir-boosted tipranavir-based regimen efficacy, safety and tolerability through week 292. RESULTS: In patients <12 years of age, 51/62 (82%) were receiving drug at week 48 and 13/62 (21%) at week 288. Among adolescents (12-18 years of age), 35/53 (66%) were receiving drug at week 48 and 2/53 (4%) at week 288. Among patients 2 to <6 years of age, 18/25 (72%) had viral loads <400 copies/mL at week 48. By week 292, 9/25 (36%) of patients had viral loads <400 copies/mL. Among older patients, week 48 responder rates were 35% (13/37 of patients 6 to <12 years of age) and 32% (17/53 of patients 12 to 18 years of age). By week 292, 6/37 (16%) of those 6 to <12 years of age and 2/53 (4%) of those 12 to 18 years of age had viral loads <400 copies/mL. Overall safety and tolerability profiles were best for children who initiated treatment between 2 and <6 years of age. Drug-related adverse events (investigator defined) were similar across all age groups (55-65%). CONCLUSIONS: Pediatric patients who begin treatment at the earlier ages, and who are stable on a ritonavir-boosted tipranavir-based regimen at week 48, generally continue to demonstrate good safety, tolerability and virologic efficacy profiles up to 292 weeks of treatment.

Antiretroviral treatment adherence in childhood and adolescence: multidisciplinary team as an associated factor in Brazil.

Our aim was to analyze factors associated with non-adherence to antiretroviral (ARV) treatment among children and adolescents. A cross-sectional study was carried out involving non-institutionalized children and adolescents between 2 and 20 years of age, addressing non-adherence to ARV treatment, which was defined as taking ≤89% of the medications on the day of the interview and the three previous days. The investigation into the association between non-compliance and the variables of interest was performed using unconditional logistic regression. The independent factors associated with non-adherence were forgetfulness (OR = 3.22; 95%CI = 1.75-5.92), difficulties coping with treatment (OR = 2.65; 95%CI = 1.03-6.79), and living with grandparents (OR = 2.28; 95%CI = 1.08-4.83), whereas a protective effect was found with participation in multidisciplinary activities (OR = 0.49; 95%CI = 0.25-0.96), i.e., this factor indicates that the exposure to the variable is beneficial, promoting adherence. We concluded that forgetting to take the medications and reporting having difficulty coping with ARV treatment are potentially modifiable factors through educational and programmatic actions. Residing with one's grandparents may strongly impact adherence to ARV treatment, indicating the need for the systematic support of these family members. Participation in multidisciplinary activities should be stimulated at health-care services.

A randomized study of tenofovir disoproxil fumarate in treatment-experienced HIV-1 infected adolescents.

BACKGROUND: There are few data on the safety and antiviral activity of tenofovir disoproxil fumarate (TDF) in HIV-1 infected adolescents. METHODS: A randomized, double-blinded, placebo-controlled study was conducted. Ninety adolescents (12 to <18 years) who were viremic while receiving antiretroviral treatment were randomized to receive TDF 300 mg (mean, 216.8 mg/m(2)) or placebo in combination with an optimized background regimen (OBR) for 48 weeks. The primary efficacy endpoint was time-weighted average change in plasma HIV-1 RNA from baseline at week 24 RESULTS: Eighty-seven subjects (45 TDF, 42 placebo) received the study drug. Through week 24, the median time-weighted average change in plasma HIV-1 RNA was not different between the TDF and placebo groups (-1.6 versus -1.6 log(10)copies/mL, P = 0.55). The percentages of subjects who achieved HIV-1 RNA <400 copies/mL were similar at week 24 (40.9 versus 41.5%). One fourth of subjects in the TDF and placebo groups (24.4 versus 28.6%) had at least 3 active agents in the OBR. Many subjects in both groups had baseline genotypic resistance to TDF (48.9 versus 33.3%). TDF was generally safe and well tolerated. There were no statistically significant differences in changes of renal function and bone mineral density between the 2 groups. CONCLUSION: This study of TDF in combination with an OBR in antiretroviral-experienced adolescents did not meet its primary or secondary efficacy endpoints. The effectiveness of the OBR and baseline genotypic resistance to TDF in both groups may have confounded the efficacy findings. No clinically relevant TDF-related renal or bone toxicities were observed in this adolescent population.

Evaluation of viral load thresholds for predicting new World Health Organization stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy.

BACKGROUND: This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly active antiretroviral therapy (HAART). METHODS: Cox proportional hazards modeling was used to assess the adjusted risk for World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥6 months. Models were fit using different VL cut-points between 400 and 50,000 copies per milliliter, with model fit evaluated on the basis of the minimum Akaike information criterion value, a standard model fit statistic. RESULTS: Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cut-points of >2600 and >32,000 copies per milliliter corresponded to the lowest Akaike information criterion values and were associated with the highest hazard ratios (2.0, P = 0.015; and 2.1, P = 0.0058, respectively) for WHO events. CONCLUSIONS: In HIV-infected Latin American children on stable HAART, 2 distinct VL thresholds (>2600 and >32,000 copies/mL) were identified for predicting children at significantly increased risk for HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors.

Improving survival in children with AIDS in Brazil: results of the second national study, 1999-2002.

The objective of this study is to characterize survival in children with AIDS diagnosed in Brazil between 1999-2002, compared with the first national study (1983-1998). This national retrospective cohort study examined a representative sample of Brazilian children exposed to HIV from mother-to-child transmission and followed through 2007. The survival probability after 60 months was analyzed by sex, year of birth and death, clinical classification, use of antiretroviral therapy (ART) and prophylaxis for opportunistic diseases. 920 children were included. The survival probability increased: comparing cases diagnosed before 1988 with those diagnosed from 2001-2002 it increased by 3.5-fold (from 25% to 86.3%). Use of ART, initial clinical classification, and final classification were significant (p < 0.001) predictors of survival. Issues regarding quality of records and care were identified. The results point to the success of the Brazilian policy of providing ART. The improvement of clinical status contributes to quality of life, while indicating challenges, particularly practices to improve long-term care.

Dyslipidemia in a cohort of HIV-infected Latin American children receiving highly active antiretroviral therapy.

In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3-5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9-6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART.

Viral load predicts new world health organization stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy, independent of CD4 T lymphocyte value.

BACKGROUND: Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. METHODS: The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age <15 years, and continuous HAART for ≥6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. RESULTS: The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load >5000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05-3.11; P = .033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. CONCLUSIONS: Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.

PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection.

PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained.

AIDS by mother-to-child transmission: survival analysis of cases followed from 1983 to 2002 in different regions of Brazil.

Antiretroviral therapy contributes to decreasing morbidity and mortality, and ultimately to increasing survival. In Brazil, there are regional differences in HIV epidemiology regarding pregnant women and children with HIV/AIDS. This study evaluates survival time after AIDS diagnosis in 914 children infected by mother-to-child transmission, reported between 1983 and 1998 and followed until 2002, in Brazil's five regions. Time between birth and HIV diagnosis decreased over the years, mainly in the South and Southeast Regions. There was a significant improvement in survival; more than 75% of cases were still living four years after diagnosis in the 1997-1998 group. This Brazilian study demonstrates that even with regional inequalities in health care infrastructure it is possible for a developing country to establish an effective system of universal and free access to antiretroviral therapy that produces a significant increase in survival for children with AIDS.