Immunologic Response to Combination Nucleoside Analogue plus Protease Inhibitor Therapy in Stable Antiretroviral Therapy–Experienced Human Immunodeficiency Virus–Infected Children (original) (raw)
Related papers
Protease Inhibitor Therapy in HIV-Infected Children
AIDS Patient Care and STDs, 2000
We reviewed the short-term response to and safety of protease inhibitor (PI) therapy in HIVinfected children by performing a retrospective chart review of open-label PI containing combination therapy at two urban pediatric HIV centers. Seventy HIV-infected children received 101 PI containing antiretroviral therapy (ART) combinations. Main outcome measures were follow-up CD4 counts, viral loads, and patient or caregiver reported compliance. During follow-up, treatment with PI ART was associated with a mean maximal increase in CD4 1 lymphocyte count of 454 3 10 6 /L and a mean maximal decrease in viral load of 1.76 log units. Of the 32 patients who achieved undetectable viral loads, 28 (87.5%) remained undetectable through a mean follow-up of 8.9 months. Patients who reported good compliance achieved a higher rate of response (92.6%) than those who reported poor compliance (61.5%). Of 14 changes made to a second PI because of treatment failure, 11 (78.6%) resulted in a positive response to the second regimen. Nineteen of 101 courses of PI therapy resulted in significant side effects, including renal complications in 8 of 21 patients treated with indinavir. PI ART was associated with substantial short-term improvement in immunological and virological parameters in this heavily pretreated cohort, with 40% of patients maintaining an undetectable viral load after 9 months of therapy. Patients who failed one PI regimen usually responded to a second regimen. There was a significant rate of side effects from PI treatment.
Clinical Infectious Diseases, 2002
Clinical, virologic, and immunologic responses to treatment that contained either indinavir or nelfinavir (both regimens included zidovudine and lamivudine) were determined in 32 children infected with human immunodeficiency virus type 1 (HIV-1) who participated for у96 weeks in a prospective, open, uncontrolled multicenter trial. The pharmacokinetics of indinavir and of nelfinavir were determined and showed large interindividual differences. After 96 weeks of therapy, 69% and 50% of the patients had an HIV-1 RNA load that was below the HIV assays' detection limits of 500 and 40 copies/mL, respectively. Virologic failure was associated with poor compliance and younger age (independent of baseline virus load and receipt of pretreatment). Relative CD4 cell counts increased significantly in relation to the median of the age-specific reference value, from a median of 44% at baseline to 94% after 96 weeks. In a high percentage of the children, clinical, virologic, and immunologic response rates to combination therapy were optimal during the initial 2 years of therapy.
Brazilian Journal of …, 2007
This study evaluates clinical, virological and immunological responses to antiretroviral (ARV) therapy based on Lopinavir/ritonovir (LPV/r) in previously protease -inhibitor-experienced children. The study included 29 Brazilian children (median age = 5.91 years) who had failed previous ARV therapy and had begun a regimen based on LPV/r. At 12 months follow-up, a good virological response to LPV/r therapy was defined as achieving an undetectable viral load or as a decrease in plasma HIV RNA levels to > 1 log. A good immunological response was defined as an increase in CD4+ cell count from baseline sufficient to attain a better CDC immune stage classification. The number of infectious episodes 12 months before and 12 months after beginning LPV/r was assessed. Sixteen (55.2%) and 19 (65.5%) of 29 patients exhibited good virological and immunological responses, respectively. Baseline CD4+ values (>500) predicted both virological and immunological responses (p<0.05). Older children were less likely to develop an immunological response (p<0.001) than younger children. Nine children receiving 3 ARV drugs plus LPV/r showed an immunological response (100%) compared to 10/20 (50%) children receiving 2 drugs plus LPV/r (p=0.01). A lower number (n<5) of infectious episodes was noted after 12 months follow-up in children using the LPV/r regimen (p=0.006). There was a positive correlation between children whose baseline CD4+ values were greater than 500 cells/mm3 and virological responses. Although virological responses to therapy were seen in about half the children (55.2%), the use of HAART containing LPV/r provided clinical and immmunological benefits.
Brazilian Journal of Infectious Diseases, 2007
This study evaluates clinical, virological and immunological responses to antiretroviral (ARV) therapy based on Lopinavir/ritonovir (LPV/r) in previously protease -inhibitor-experienced children. The study included 29 Brazilian children (median age = 5.91 years) who had failed previous ARV therapy and had begun a regimen based on LPV/r. At 12 months follow-up, a good virological response to LPV/r therapy was defined as achieving an undetectable viral load or as a decrease in plasma HIV RNA levels to ≥ ≥ ≥ ≥ ≥ 1 log. A good immunological response was defined as an increase in CD4 + cell count from baseline sufficient to attain a better CDC immune stage classification. The number of infectious episodes 12 months before and 12 months after beginning LPV/r was assessed. Sixteen (55.2%) and 19 (65.5%) of 29 patients exhibited good virological and immunological responses, respectively. Baseline CD4 + values (>500) predicted both virological and immunological responses (p<0.05). Older children were less likely to develop an immunological response (p<0.001) than younger children. Nine children receiving 3 ARV drugs plus LPV/r showed an immunological response (100%) compared to 10/20 (50%) children receiving 2 drugs plus LPV/r (p=0.01). A lower number (n<5) of infectious episodes was noted after 12 months follow-up in children using the LPV/r regimen (p=0.006). There was a positive correlation between children whose baseline CD4 + values were greater than 500 cells/mm 3 and virological responses. Although virological responses to therapy were seen in about half the children (55.2%), the use of HAART containing LPV/r provided clinical and immmunological benefits.
Sri Lanka Journal of Child Health
Background: Children exposed to single dose nevirapine at birth, if tested human immunodeficiency virus (HIV) positive, cannot be given nevirapine based anti-retroviral therapy (ART). Therefore protease inhibitor (PI) based combinations are being used as first line therapy in such children. However, experience is limited regarding their efficacy and adverse effects in the Indian population. Objectives: To document clinical and immunological responses to PI based regimens as first line therapy in HIV infected children less than 5 years old compared to responses to standard nonprotease inhibitor (NPI) first line regimens recommended by National AIDS Control Organisation and World Health Organisation. Method: An observational prospective cohort study was conducted in a tertiary care hospital in Surat, India, from December 2011 to June 2013 on children less than 5 years of age with confirmed HIV status. At diagnosis, clinical staging, growth parameters and CD4 levels were assessed and the children were allotted to NPI and PI groups depending on prior nevirapine exposure. Clinical, immunological and biochemical alterations after ART initiation were assessed and compared after 6 months of therapy. Results: During the study period, there were 43 children less than 5 years of age with confirmed HIV status. Children in both NPI and PI groups showed significant improvement in clinical stage of the disease after 6 months of therapy (P<0.001).
Journal of Infectious Diseases, 2001
This study investigated whether immune restoration occurred in 26 human immunodeficiency virus (HIV) type 1-infected children treated first with indinavir for 16 weeks and then with combination antiretroviral therapy for 12 years. Compared with baseline, a significant, although modest, decrease in virus loads (maximum median, Ϫ0.86 log 10 ) and increase in the number of CD4 + lymphocytes, especially naive cells, were observed at several time points after 2 years. A maximum of 7% of treated children achieved undetectable viremia. There was a marked increase in the proliferative response and skin reactivity to recall antigens. However, responses to an HIV antigen remained depressed, and the production of interleukin-12 remained unchanged and abnormally low. The magnitude of virus suppression did not correlate with these measures of functional immune reconstitution. These findings suggest that long-term nonsuppressive antiretroviral therapy can induce limited improvement in immune function in pediatric AIDS patients and that the effect of suppressive treatments should be investigated.
Protease inhibitor therapy in children with perinatally acquired HIV infection
AIDS, 1997
Objective: To review the short-term response and safety of protease inhibitor therapy in HIV-infected children. Design: Retrospective chart review of open-label protease inhibitor-containing combination therapy. Setting: Two urban pediatric HIV centers. Patients: Twenty-eight HIV-infected children were prescribed 30 protease inhibitorcontaining antiretroviral therapy combinations. The median age at initiation of protease inhibitor antiretroviral therapy was 79 months. Patients had been on previous antiretroviral therapy for a mean of 45.5 months. Results: Of the 28 children who completed at least 1 month of therapy, 26 experienced marked virologic and immunologic improvement (mean maximal decrease in viral load 1.90 log 10 copies/ml; SD, 0.8; mean maximal rise in CD4+ lymphocytes of 279 × 10 6 /l; SD, 300 × 10 6 /l). Eleven patients achieved a viral nadir of < 400 copies/ml, and seven sustained this level of viral suppression for a mean of 6 months. Indinavir use was associated with a high incidence of renal side-effects, including two patients who developed interstitial nephritis. Two patients on ritonavir experienced a significant elevation of liver enzymes. Conclusions: Protease inhibitor therapy was associated with substantial short-term virologic and immunologic improvement in this primarily heavily pretreated cohort, with 25% maintaining a viral load of < 400 copies/ml after 6 months of therapy. There was a significant rate of adverse events. Pharmacokinetic and safety data are needed to guide aggressive antiretroviral therapy in HIV-infected children, and further treatment options are required for those failing or intolerant to the available protease inhibitors.