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The certainty that the homeostatic mechanisms are able to compensate for this mtDNA depletion in patients receiving stavudine plus didnosine(d4T+ ddI), an antiretroviral combination with great in vitro and in vivo capacity to decrease mtDNA is determined. The study concludes that treatment with ddT=ddI is associated with decreased mitochondrial mass and mtDNA content but that cytochrome c oxidase subnit II (COX-II) expression and COX activity remain unaltered.

This case series describes 4 children with vertically acquired human immunodeficiency virus (HIV) infection who exhibited immunologic, virologic, and clinical stability while on a protease inhibitor-containing highly active antiretroviral therapy (HAART) regimen, yet demonstrated significant cognitive decline as measured by standardized intelligence tests. A retrospective review of 107 patient records of children with HIV infection on HAART treatment protocols was conducted. Four patients were identified who responded to protease inhibitor-containing HAART therapy with sustained viral load suppression, and stable immunologic and medical parameters, yet demonstrated significant cognitive decline. Such discordance between biological and clinical markers previously has been reported in adults with HIV disease but not in children. This observed decline in neurocognitive functioning despite stable medical parameters suggests that HAART regimens that are effective for systemic disease may not be as effective for the central nervous system (CNS), perhaps because the antiretrovirals do not penetrate adequately into the CNS. Of note, 3 of these 4 patients did not have zidovudine (ZDV) included in their HAART regimen. The only patient who was treated with ZDV containing regimen received 90 mg/[m.sup.2] every 6 hours, which is at the lower end of the recommended ZDV pediatric full-dose range (90 mg/[m.sup.2] to 120 mg/[m.sup.2]). Two of the 4 patients began ZDV at 120 mg/[m.sup.2] every 6 hours following the decline in their cognitive test scores and subsequently showed improved or stable functioning as evidenced by the results of follow-up psychometric testing. Long-term prospective studies using both systemic and CNS measures are necessary to further investigate the effects of HAART in children with HIV disease. Longitudinal cognitive assessments of children receiving HAART appear indicated to identify cognitive decline and to provide appropriate therapeutic intervention when manifestations of HIV-related CNS disease progression occur. Pediatrics 2003;112:679-684; HIV, HAART., ABBREVIATIONS. HIV, human immunodeficiency virus; HAART, highly active antiretroviraI therapy; CNS, central nervous system; ZDV, zidovudine; AIDS, acquired immunodeficiency syndrome; d4T, stavudine; NVP, nevirapine; CSF, cerebrospinal fluid; ddI, didanosine; NFV, [...]

Research has been conducted on protease inhibitor atazanavir. The dose levels of this medication have been compared with those of nelfinavir as a monotherapy and in combination with didanosine and stavudine, and the results of this clinical trial carried out to compare safety, tolerability and antiretroviral efficacy of these three doses are reported.

Research has been conducted on zidovudine resistance mutations. The role of these mutations in virologic response to treatment with zidovudine or stavudine in combination with lamivudine and indinavir has been investigated, and the results demonstrate that zidovudine resistance mutations do not preclude a durable response to treatment with a three-drug regimen in the patients.

Research has been conducted on enteric-coated didanosine beadlets administered once daily. The activity and safety of the capsules which contain these beadlets have been compared with stavudine and nelfinavir, and the results are reported.

Research has been conducted on stavudine. The study of the phenotypic susceptibility level of this drug associated with a diminished virologic response to stavudine therapy has been carried out via phenotyping, performed on the baseline HIV isolates from the patients who received stavudine monotherapy, and the details are reported.

Research has been conducted on the abnormal body fat distribution in HIV-infected persons. Results demonstrate that the prevalence of lipodystrophy is higher among the patients treated with stavudine for a longer period of time.

Research has been conducted on the anti-HIV agent stavudine. The reaction of the 5'-O-protected derivative of this agent with LTMP has been investigated in the presence of HMPA in an attempt to lithiate vinylic hydrogens and the results indicate that the reaction has triggered anionic silyl migration to produce 3'-C-silylated product.