Long-term follow-up of 414 HIV-infected Romanian children and adolescents receiving lopinavir/ritonavir-containing highly active antiretroviral therapy.

BACKGROUND: There are no published reports of the long-term safety and effectiveness of highly active antiretroviral therapy for children and adolescents living in resource-limited settings or of large cohorts of HIV-infected children and adolescents treated long-term (>48 weeks) with lopinavir/ritonavir-containing highly active antiretroviral therapy. OBJECTIVES: The purpose of this work was to evaluate the long-term outcomes of treatment of HIV-infected children and adolescents with lopinavir/ritonavir-containing highly active antiretroviral therapy in a resource-limited setting. METHODS: We studied an inception cohort of 414 HIV-infected children receiving lopinavir/ritonavir-containing highly active antiretroviral therapy between November 2001 and August 2006 at the Romanian-American Children's Center in Constanta, Romania. The center provides comprehensive primary and HIV specialty care and treatment to all known HIV-infected children and adolescents living in Constanta. We measured safety and effectiveness by the percentage of children remaining on treatment, rates of mortality, and changes in plasma HIV RNA concentrations and CD4+ lymphocyte counts. RESULTS: The study population consisted predominantly of antiretroviral drug-experienced older children and adolescents with advanced HIV disease. Treatment was well tolerated, with 337 children (81%) remaining on therapy after a median duration of >4 years. Thirty-seven deaths occurred; the death rate compared favorably to prospectively collected historical data. The most recent on-treatment plasma HIV RNA concentration was <400 copies per milliliter in 192 of 265 children tested. The mean baseline CD4+ lymphocyte count was 292 cells per microliter (n = 299); the mean change from baseline was +266 (n = 284), +317 (n = 260), +343 (n = 176), and +270 cells per microliter (n = 121) after 1, 2, 3, and 4 years of treatment, respectively. CONCLUSIONS: Highly active antiretroviral therapy can be administered safely and effectively to children and adolescents in resource-limited settings. Lopinavir/ritonavir-containing highly active antiretroviral therapy is a safe, effective, and durable treatment option for antiretroviral drug-experienced older children and adolescents with advanced HIV disease.

Biologic and social determinants of sequelae and long-term survival of pediatric HIV in Romania.

PURPOSE: The aim of the study is to investigate the effect of social context and clinical factors on survival in a cohort of 333 children to identify issues useful in the treatment and care of human immunodeficiency virus (HIV)-infected youth in developing countries. METHODS: A prospective cohort study design was used, and data were gathered at baseline and 1-year follow-up. The study cohort consisted of children given a diagnosis of HIV between 1995 and 1999 and receiving medical care in Constanta, Romania. Data were examined by means of multivariate Cox regression analysis models. RESULTS: The majority of the cohort were in the moderate (41%) or severe (40%) stages of HIV at baseline. Multivariate analysis indicated that social-context factors were the most significant determinants of HIV survival. The hazard for death for those with mothers or fathers with a higher level of education was approximately one quarter (relative hazard, 0.3-0.4; confidence interval, 0.1-1.0) that for a parent with a lower level of education. Subjects with employed mothers were four times more likely to survive than subjects with unemployed mothers. CONCLUSIONS: Results suggest that recognition of social-context risk factors for HIV disease progression and survival is important in developing countries, as it is in developed countries.

High prevalence of hepatitis B virus markers in Romanian adolescents with human immunodeficiency virus infection.

BACKGROUND: We evaluated the frequency of hepatitis coinfection in Romanian adolescents who were diagnosed with human immunodeficiency virus (HIV) infection prior to 1995. METHODS: One hundred sixty-one adolescents (13-18 years of age) with symptomatic HIV infection, but without signs of hepatic dysfunction, and 356 age-matched, HIV-uninfected controls underwent laboratory testing for markers of parenterally acquired hepatitis virus infection. RESULTS: Seventy-eight percent of HIV-infected adolescents had markers of past or present hepatitis B virus (HBV) infection, as compared with 32% of controls ( P = .0001). The prevalence of HBV replicative markers was more than 5-fold higher in HIV-infected adolescents as compared with controls: 43.4% vs 7.9% ( P = .0001), respectively, for hepatitis B surface antigen (HBsAg); and 11.2% vs 2.2% ( P = .0001), respectively, for hepatitis B e antigen (HBeAg). The prevalence of HBsAg chronic carriers and the presence of HBV replicative markers was significantly higher in patients with immunologically defined AIDS (CD4+ cell counts < 200 cells/mcL): 59.6% vs 34.6% ( P = .02) for HBsAg and 22.8% vs 5.7 %, ( P = .002) for HBV DNA. After 1 year of follow-up, the proportion of those who cleared the HBeAg was considerably lower in severely immunosuppressed coinfected patients: 4.7% vs 37.1% ( P = .003). Four additional HIV-infected adolescents became HBsAg-positive over the term of follow-up (incidence rate, 24.9/1000 person-years), despite a record of immunization against hepatitis B. CONCLUSIONS: A substantial percentage of HIV-infected and HIV-uninfected Romanian adolescents have evidence of past or present HBV infection. In HIV-infected adolescents, the degree of immunosuppression is correlated with persistence of HBV replicative markers, even in the absence of clinical or biochemical signs of liver disease.

Longitudinal study of the prevalence and prognostic implications of oral manifestations in romanian children infected with human immunodeficiency virus type 1.

OBJECTIVE: We evaluated the prevalence and predictive value for human immunodeficiency virus (HIV) disease progression of oral manifestations in Romanian children. METHODS: A nonrandom sample of 238 HIV-infected children was followed prospectively between 1998 and 2001 at the Romanian-American Children's Center in Constanta, Romania. Study subjects underwent comprehensive annual oral examinations. Oral manifestations of interest, demographic data and other selected medical information were recorded at baseline and at each subsequent visit. Descriptive statistics and survival analysis methods were used in the study. A level of statistical significance of alpha = 0.05 was used. RESULTS: The study subjects' mean age was 9.9 +/- 1.2 (SD) years. The most common oral lesions were gingivitis (49%), parotid enlargement (13%) and oral candidiasis (11%). Oral candidiasis was associated with progression to acquired immunodeficiency syndrome or death (whichever occurred first) (log rank P = 0.03) and with death (log rank P < 0.001). Oral hairy leukoplakia also was associated with progression to death (log rank P = 0.001). The risk of dying was 3.43 (95% confidence interval, 1.86-6.34; P < 0.001) for children who had oral candidiasis at baseline and 4.62 (95% confidence interval, 1.67-12.77; P = 0.003) for those who had oral hairy leukoplakia. CONCLUSIONS: Oral manifestations occur commonly among HIV-infected Romanian children. Oral candidiasis and oral hairy leukoplakia were positive predictors of HIV disease progression.

Alternatives to HIV-RNA and CD4 count to monitor HIV disease progression: a prospective cohort study in Romania.

Little evidence exists on how to efficiently and effectively monitor HIV-disease progression in developing countries. Better understanding regarding cost-effective tests may help to resolve questions regarding treatment. A prospective cohort study was conducted with a 1-year follow-up period. Immune complex-dissociated (ICD) p24 antigen (ICD p24Ag), alone or in combination with HIV p24 antibody (p24Ab), was compared to HIV-RNA and CD4+ count in a cohort of 160 HIV-infected adolescents in Romania. The main outcome measure was disease progression, defined as >50,000 copies/ml of HIV-RNA or death. Among the 160 adolescents, a higher mean ICD p24Ag was significantly associated with clinical disease classification (CDC), plasma HIV-RNA concentration, and p24Ab. Multivariate logistic regression showed detectable ICD p24Ag had an odds ratio of 3.7 (95% CI 1.4-9.7) for disease progression in comparison to undetectable ICD p24Ag. ICD p24Ag is of value in determining the prognosis of disease in HIV-1-infected adolescents in developing countries. Additional studies for validation of this assay for HIV clades primarily affecting developing countries, are now needed.

High prevalence of hepatitis B virus markers in romanian adolescents with human immunodeficiency virus infection.

BACKGROUND: We evaluated the frequency of hepatitis coinfection in Romanian adolescents who were diagnosed with human immunodeficiency virus (HIV) infection prior to 1995. METHODS: One hundred sixty-one adolescents (13-18 years of age) with symptomatic HIV infection, but without signs of hepatic dysfunction, and 356 age-matched, HIV-uninfected controls underwent laboratory testing for markers of parenterally acquired hepatitis virus infection. RESULTS: Seventy-eight percent of HIV-infected adolescents had markers of past or present hepatitis B virus (HBV) infection, as compared with 32% of controls (P = .0001). The prevalence of HBV replicative markers was more than 5-fold higher in HIV-infected adolescents as compared with controls: 43.4% vs 7.9% (P = .0001), respectively, for hepatitis B surface antigen (HBsAg); and 11.2% vs 2.2% (P = .0001), respectively, for hepatitis B e antigen (HBeAg). The prevalence of HBsAg chronic carriers and the presence of HBV replicative markers was significantly higher in patients with immunologically defined AIDS (CD4+ cell counts < 200 cells/mcL): 59.6% vs 34.6% (P = .02) for HBsAg and 22.8% vs 5.7%, (P = .002) for HBV DNA. After 1 year of follow-up, the proportion of those who cleared the HBeAg was considerably lower in severely immunosuppressed coinfected patients: 4.7% vs 37.1% (P = .003). Four additional HIV-infected adolescents became HBsAg-positive over the term of follow-up (incidence rate, 24.9/1000 person-years), despite a record of immunization against hepatitis B. CONCLUSION: A substantial percentage of HIV-infected and HIV-uninfected Romanian adolescents have evidence of past or present HBV infection. In HIV-infected adolescents, the degree of immunosuppression is correlated with persistence of HBV replicative markers, even in the absence of clinical or biochemical signs of liver disease.

Comprehensive pediatric human immunodeficiency virus care and treatment in Constanta, Romania: implementation of a program of highly active antiretroviral therapy in a resource-poor setting.

BACKGROUND: Relatively few human immunodeficiency virus (HIV)-infected children worldwide have access to care and treatment. The Romanian-American Children's Center, a collaborative project of a U.S. health care institution and the Romanian government, has established a comprehensive program of highly active antiretroviral therapy for children in Constanta, Romania. OBJECTIVES: To describe the design and outcomes of a program of pediatric HIV/acquired immunodeficiency syndrome (AIDS) care and treatment in a resource-poor setting. SETTING: Outpatient center providing comprehensive primary and HIV/AIDS specialty care and treatment to all known HIV-infected children living in Constanta County, Romania. OUTCOMES: As of August 2003, a total of 452 children were receiving highly active antiretroviral therapy. Therapy has been well-tolerated, with approximately 90% of children continuing to receive treatment after a median duration of follow-up of 67 weeks. Normal weight and height growth velocities have been observed among treated children. Marked decreases have been observed in rates of hospitalization and mortality. The mean change in CD4+ lymphocyte count for 173 children who have both a baseline count and at least 1 follow-up count is +284 cells/microL (P < 0.0001). CONCLUSIONS: Highly active antiretroviral therapy can be administered safely and effectively to children in a resource-poor setting, with outcomes comparable with those observed in U.S. pediatric antiretroviral clinical trials.

The effects of long-term herbal treatment for pediatric AIDS.

This paper presents our long-term (1992-2000) treatment of pediatric Acquired Immune Deficiency Syndrome (AIDS) patients (maximum 100 children, last three years 65) using native herbal remedies in a voluntary medical assistance program in Constanta, Romania. We primarily report the progress of 10 children at a facility called the "House of Tomorrow" and three other facilities. The long-term (8 years and 8 months) treatment contributed to a drop of the amount of Human Immunodeficiency Virus Ribonucleic Acids (HIV-RNA) below the measurable level for 9 out of 10 patients at the "House of Tomorrow." Furthermore, the treatment led to preservation and increase of the cluster of differentiation (CD4) count, a remarkable decrease in mortality rate, as well as the maintenance of a good quality of life. It took one to three years for the beneficial effects of the treatment to emerge. No side-effects were recognized either clinically or biochemically, nor was there any emergence of drug-resistant strains of HIV as seen with anti-HIV chemical treatments. This paper also refers to which herbal remedies were used and their general mechanism of action.