Aging, neurocognitive impairment and adherence to antiretroviral therapy in human immunodeficiency virus-infected individuals

ABSTRACT Background/objective: There is an increasing number of older patients with human immunodeficiency virus infection due to the success of antiretroviral therapy, the improved prognosis and life expectancy of patients, and the higher number of new infections among older individuals. The main objective of the present study was to compare the characteristics of older human immunodeficiency virus patients with those of younger patients. Materials and methods: We conducted a cross-sectional study with human immunodeficiency virus-infected patients who were treated at the Specialized Care Service (Serviço de Assistência Especializada) for human immunodeficiency virus/AIDS in the city of Pelotas, South Brazil. Sociodemographic information as well as data on human immunodeficiency virus infection and treatment were collected. All participants underwent psychiatric and neurocognitive assessments, and their adherence to antiretroviral therapy was evaluated. Results: A total of 392 patients participated in the study, with 114 patients aged 50 years and older. The characteristics showing significant differences between older and younger human immunodeficiency virus-infected patients included race/ethnicity, comorbidities, duration and adherence to antiretroviral therapy, currently undetectable viral load, and cognitive impairment. Compared to younger patients, older patients were at higher risk of exhibiting cognitive impairment [OR 2.28 (95% CI: 1.35-3.82, p = 0.002)] and of having increased adherence to antiretroviral therapy [OR 3.11 (95% CI: 1.67-5.79, p < 0.001)]. Conclusions: The prevalence of neurocognitive impairment remained high in human immunodeficiency virus-infected patients despite antiretroviral therapy. In the present study, the prevalence of this type of impairment was significantly higher in patients aged ≥50 years, most likely due to aging, human immunodeficiency virus infection, and a possible synergistic effect between these factors. Despite this higher prevalence, older patients exhibited higher rates of adherence to antiretroviral therapy and of undetectable human immunodeficiency virus viral load.

Aging, neurocognitive impairment and adherence to antiretroviral therapy in human immunodeficiency virus-infected individuals.

BACKGROUND/OBJECTIVE: There is an increasing number of older patients with human immunodeficiency virus infection due to the success of antiretroviral therapy, the improved prognosis and life expectancy of patients, and the higher number of new infections among older individuals. The main objective of the present study was to compare the characteristics of older human immunodeficiency virus patients with those of younger patients. MATERIALS AND METHODS: We conducted a cross-sectional study with human immunodeficiency virus-infected patients who were treated at the Specialized Care Service (Serviço de Assistência Especializada) for human immunodeficiency virus/AIDS in the city of Pelotas, South Brazil. Sociodemographic information as well as data on human immunodeficiency virus infection and treatment were collected. All participants underwent psychiatric and neurocognitive assessments, and their adherence to antiretroviral therapy was evaluated. RESULTS: A total of 392 patients participated in the study, with 114 patients aged 50 years and older. The characteristics showing significant differences between older and younger human immunodeficiency virus-infected patients included race/ethnicity, comorbidities, duration and adherence to antiretroviral therapy, currently undetectable viral load, and cognitive impairment. Compared to younger patients, older patients were at higher risk of exhibiting cognitive impairment [OR 2.28 (95% CI: 1.35-3.82, p=0.002)] and of having increased adherence to antiretroviral therapy [OR 3.11 (95% CI: 1.67-5.79, p<0.001)]. CONCLUSIONS: The prevalence of neurocognitive impairment remained high in human immunodeficiency virus-infected patients despite antiretroviral therapy. In the present study, the prevalence of this type of impairment was significantly higher in patients aged ≥50 years, most likely due to aging, human immunodeficiency virus infection, and a possible synergistic effect between these factors. Despite this higher prevalence, older patients exhibited higher rates of adherence to antiretroviral therapy and of undetectable human immunodeficiency virus viral load.

Protective effects of naringin against gp120-induced injury mediated by P2X7 receptors in BV2 microglial cells.

This study was aimed at exploring the effects of P2X7 receptors on gp120-induced injury and naringin's protective effects against gp120-induced injury in BV2 microglia. BV2 microglia injury model was established by gp120 treatment and MTS assay was used to verify whether naringin has a cell-protective effect against gp120-induced injury. Changes in P2X7 receptor expression were assayed using RT-PCR, qPCR, and western blot. Results showed that the ODs of the Ctrl, gp120, gp120+naringin, and gp120+BBG groups were 0.91 ± 0.10, 0.71 ± 0.09, 0.83 ± 0.10, and 0.83 ± 0.10, respectively. Compared to the control group, the gp120 group showed a significantly decreased cell survival rate. Cell survival rates of the gp120+naringin group increased significantly compared to those of the gp120 group, while no difference was observed when compared to the gp120+BBG group. The relative P2X7 mRNA expression levels in the Ctrl, gp120, gp120+naringin, and gp120+BBG groups were 0.73 ± 0.06, 1.05 ± 0.06, 0.78 ± 0.05, and 0.81 ± 0.04, respectively. The corresponding P2X7 protein expression levels were 0.46 ± 0.04, 0.79 ± 0.04, 0.38 ± 0.07, and 0.42 ± 0.06. P2X7 mRNA and protein expression in the gp120 group increased significantly compared to those in the control group, and declined in the gp120+naringin group compared to those in the gp120 group. Therefore, P2X7 receptors might be involved in gp120-induced injury in BV2 microglia, and naringin might play a protective role by inhibiting the up-regulated expression of P2X7 receptors.

Relation of cerebrospinal fluid/plasma HIV-RNA discordance with neurocognitive impairment.

Neurological involvement is common in patients infected with HIV. The effectiveness of antiretroviral drugs in lowering the levels of HIV-RNA in cerebrospinal fluid (CSF) is limited by their inability to cross the blood-brain barrier. Discordance in CSF/plasma HIV-RNA levels may have a bearing on the progression of neurological disease in these patients. We report a woman with subacute neurocognitive impairment and abnormal findings on brain MRI, in whom there was a discordance between CSF/plasma HIV-RNA levels. The patient improved after a change in her highly active antiretroviral therapy (HAART) regimen. We also reviewed the available literature on the subject and found seven articles describing 27 patients.

Cognitive impairment and antiretroviral treatment in a Peruvian population of patients with human immunodeficiency virus.

BACKGROUND: HIV-associated cognitive impairment occurs even in the early stages of infection. Short-term memory, psychomotor speed, attention, and executive functioning are the main capacities affected. Controversy exists regarding whether highly active antiretroviral therapy (HAART) is helpful in combating this process. The objective of the present study is to determine the association between cognitive impairment and HAART in HIV-infected patients from Hospital Regional de Huacho. METHODS: Prospective study of HIV patients meeting criteria to start HAART. Twenty-one HIV-positive patients were recruited between April and July 2011. Researchers administered a standardised neuropsychological test battery before and 4 weeks after onset of HAART. Psychomotor speed, executive function, short term memory (visual and verbal), attention, and visuospatial performance were evaluated. RESULTS: Nineteen patients completed the study (14 males and 5 females). In the pre-HAART evaluation, most patients scored below average on the executive function and psychomotor speed subtests. Psychomotor speed and immediate visual memory improved significantly after four months of treatment with HAART. CONCLUSIONS: Some degree of cognitive decline may present even in the early and asymptomatic stages of HIV infection. The benefits of antiretroviral treatment for cognitive performance can be detected after only a few weeks of follow-up.

Neurocognitive function in HIV-positive children in a developing country.

OBJECTIVES: We aimed to characterize neurological outcomes and determine the prevalence of HIV encephalopathy in a cohort of HIV-infected children in Jamaica. METHODS: Data for 287 HIV-infected children presenting between 2002 and 2008 were reviewed and neurological outcomes characterized. A nested case-control study was conducted between July and September 2009 used 15 randomly selected encephalopathic HIV-infected children aged 7-10 years and 15 matched controls (non-encephalopathic HIV-infected). Their neurocognitive functions were evaluated using clinical assessment and standardized tests for intelligence, short term memory (visuo-spatial and auditory), selective attention, and fine motor and coordination functions. Outcomes were compared using Fisher's exact test and the Mann-Whitney U-test. RESULTS: Sixty-seven (23.3%) children were encephalopathic. The median age at diagnosis of HIV encephalopathy was 1.6 years (interquartile range (IQR) 1.1-3.4 years). Predominant abnormalities were delayed milestones (59, 88.1%), hyperreflexia (59, 86.5%), spasticity (50, 74.6%), microcephaly (42, 61.7%), and quadriparesis (21, 31.3%). The median age of tested children was 8.7 years (IQR 7.6-10.8 years) in the encephalopathic group and 9 years (IQR 7.4-10.7 years) in the non-encephalopathic group. Encephalopathic children performed worse in all domains of neurocognitive function (p<0.05). CONCLUSIONS: A high prevalence of HIV encephalopathy was noted, and significant neurocognitive dysfunction identified in encephalopathic children. Optimized management through the early identification of neurological impairment and implementation of appropriate interventions is recommended to improve quality of life.

[Mirtazapine and antiretroviral therapy in the treatment of progressive multifocal leukoencephalopathy associated with HIV-1 infection: report of a case and review of literature]. / Tratamiento conjunto con mirtazapina y terapia antiretroviral para la leucoencefalopatía multifocal progresiva asociada a infección por VIH-1: presentación de un caso clínico y revisión de la literatura.

We report a 43 years old HIV-1 infected male who developed a severe subacute neurological damage because of a progressive multifocal leukoencephalopathy confirmed by PCR for JC virus. The patient was treated with antiretroviral therapy in adequate doses for CNS penetration and mirtazapine, an antidepressant inhibitor of serotonin receptors. His evolution during one year follow up has been favorable in both, clinically and images.

Tratamiento conjunto con mirtazapina y terapia antiretroviral para la leucoencefalopatía multifocal progresiva asociada a infección por VIH-1: presentación de un caso clínico y revisión de la literatura / Mirtazapine and antiretroviral therapy in the treatment of progressive multifocal leukoencephalopathy associated with HIV-1 infection: report of a case and review of literature

We report a 43 years old HIV-1 infected male who developed a severe subacute neurological damage because of a progressive multifocal leukoencephalopathy confirmed by PCR for JC virus. The patient was treated with antiretroviral therapy in adequate doses for CNS penetration and mirtazapine, an antidepressant inhibitor of serotonin receptors. His evolution during one year follow up has been favorable in both, clinically and images.

Se presenta el caso clínico de un paciente de sexo masculino, de 43 años portador de VIH que desarrolló un grave daño neurológico subagudo debido a una leucoencefalopatía multifocal progresiva diagnosticada mediante reacción de polimerasa en cadena de virus JC. El paciente fue tratado con terapia anti-retroviral de penetración eficiente al SNC y con mirtazapina, un antidepresivo inhibidor de los receptores de serotonina. Su evolución durante un año de seguimiento ha sido favorable tanto del punto de vista clínico como de imágenes.

Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature / Complicações neurológicas causadas pelo citomegalovírus em pacientes com AIDS: estudo retrospectivo de 13 casos e revisão da literatura

Neurological disorders caused by Cytomegalovirus (CMV) in patients with Acquired Immunodeficiency Syndrome (AIDS) are rarely reported in the Highly Active Antiretroviral Therapy (HAART) period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in São Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF) using Polymerase Chain Reaction (PCR). Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69 percent) were men. At admission all patients were aware of their HIV status and only four (31 percent) patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62 percent) patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62 percent), polyradiculopathy (n = 7; 54 percent), focal encephalitis (rhombencephalitis) (n = 1; 8 percent), and ventriculo-encephalitis (n = 1; 8 percent). Seven (54 percent) patients presented extra-neural CMV disease and four (31 percent) had retinitis. The median of CD4+ T-cell count was 13 cells/µL (range: 1-124 cells/µL). Overall in-hospital mortality was 38 percent. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50 percent) and five patients used ganciclovir and foscarnet (in-hospital mortality: 20 percent). None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.

As complicações neurológicas causadas pelo Citomegalovírus (CMV) em pacientes com aids são raramente relatadas na era HAART. O objetivo deste estudo foi descrever as principais características clínicas e laboratoriais de pacientes com complicações neurológicas associadas ao CMV em pacientes com aids admitidos em centro de referência em Sao Paulo, Brasil. A doença citomegálica precisou da identificação do vírus no líquor mediante a reação em cadeia da polimerase (PCR). Treze casos foram identificados entre janeiro de 2004 e dezembro de 2008. A mediana da idade foi 38 anos e nove (69 por cento) eram homens. Na admissão, todos os pacientes sabiam do seu status sorológico para o HIV e apenas quatro (31 por cento) pacientes usavam HAART. A doença citomegálica foi a primeira doença definidora de aids em oito (62 por cento) pacientes. As síndromes neurológicas identificadas foram: encefalite difusa (n = 7; 62 por cento), polirradiculopatia (n = 7; 54 por cento), encefalite focal (romboencefalite) (n = 1; 8 por cento), e ventrículo-encefalite (n = 1; 8 por cento). Sete (54 por cento) pacientes apresentaram doença citomegálica fora do sistema nervoso e quatro (31 por cento) tiveram retinite. A mediana da contagem de células CD4+ foi 13 células/µL. A mortalidade global durante a internação foi 38 por cento. Oito pacientes usaram ganciclovir ou foscarnet (mortalidade: 50 por cento) e cinco pacientes usaram ganciclovir e foscarnet (mortalidade: 20 por cento). Nenhum paciente apresentou critérios diagnósticos da síndrome inflamatória de reconstituição imunológica. Quatro pacientes foram perdidos do acompanhamento ambulatorial e três pacientes apresentaram reconstituição imunológica e descontinuaram as profilaxias secundárias. Embora raras, as particulares síndromes neurológicas causadas pelo CMV continuam causando elevada mortalidade em pacientes com aids. A sobrevida depende do uso de terapia antiviral efetiva contra o CMV e a introdução oportuna do HAART.

Implications of efavirenz for neuropsychiatry: a review.

Antiretroviral therapy has revolutionized the treatment of the human immunodeficiency virus because it has improved the clinical outcomes of patients. It is essential that these drugs cross the blood-brain barrier, since the virus is present in the central nervous system (CNS). Efavirenz passes through this barrier satisfactorily and can reduce the deleterious central effects of the human immunodeficiency virus. However, patients treated with efavirenz have been observed to experience psychiatric symptoms such as mania, depression, suicidal thoughts, psychosis, and hallucinations. The aim of this review is to describe the pharmacokinetic and pharmacodynamic properties of efavirenz and its major neuropsychiatric symptoms and the neurochemical pathways associated with these changes in the CNS. The databases Medline and Lilacs were used to search for review articles and preclinical and clinical research articles published from January 1996 to 2010. The search terms used were efavirenz, central nervous system, neuropsychiatry, neurotransmitters, adverse effects, and neurochemistry. Subject categories considered included effects on viral replication, pharmacokinetic and pharmacodynamic properties of efavirenz, and neuropsychiatric adverse effects including time course, duration, and probable mechanisms involved. The mechanisms involved in these changes include interference with cytochrome P450 enzymes, cytokines, tryptophan-2-3-dioxygenase, and brain creatine kinase.

Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature.

Neurological disorders caused by Cytomegalovirus (CMV) in patients with Acquired Immunodeficiency Syndrome (AIDS) are rarely reported in the Highly Active Antiretroviral Therapy (HAART) period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in São Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF) using Polymerase Chain Reaction (PCR). Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69%) were men. At admission all patients were aware of their HIV status and only four (31%) patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62%) patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62%), polyradiculopathy (n = 7; 54%), focal encephalitis (rhombencephalitis) (n = 1; 8%), and ventriculo-encephalitis (n = 1; 8%). Seven (54%) patients presented extra-neural CMV disease and four (31%) had retinitis. The median of CD4+ T-cell count was 13 cells/µL (range: 1-124 cells/µL). Overall in-hospital mortality was 38%. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50%) and five patients used ganciclovir and foscarnet (in-hospital mortality: 20%). None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.

Good neurocognitive performance measured by the international HIV dementia scale in early HIV-1 infection.

OBJECTIVE: To evaluate neurocognitive performance in patients with preserved immunological status using the International HIV Dementia Scale (IHDS) and compare patients on and off highly active antiretroviral therapy (HAART). DESIGN: Cross-sectional study. METHODS: Outpatients with more than 350 CD4 cells per cubic millimeter underwent evaluation by means of the IHDS, a cross-cultural scale designed to identify HIV-positive patients at risk for dementia. RESULTS: A total of 260 patients were included, 158 on HAART and viral load <1000 copies per mL and 102 treatment naïve. Mean age was 38.2 (SD 8.03) years, 86% were male. Mean score was 10.9 (SD 1.77). Only age correlated with a significantly different score; younger patients performed better. When patients on and off HAART were compared, we found no significant differences in age, sex, time from diagnosis, educational level, risk factor for HIV acquisition, and current CD4 count. CD4 nadir was lower for patients on HAART: 246.0 (200.95) vs. 492.7 (233.33), P < 0.001. There was no difference between the scores obtained by patients on and off HAART (mean 11.0, SD 2.08; mean 10.8, SD 1.17; respectively, P = 0.70). There was no difference according to efavirenz use. CONCLUSIONS: Patients with preserved immunity performed well on IHDS. It didn't seem to be any difference between patients on and off HAART regarding neurocognitive status.

Incidence and prevalence of HIV encephalopathy in children with HIV infection receiving highly active anti-retroviral therapy (HAART).

OBJECTIVE: To describe neurologic outcomes in children infected with HIV in the era of highly active anti-retroviral therapy (HAART), including rates of progressive HIV encephalopathy (PHE) and clinical sequelae among PHE survivors. STUDY DESIGN: Neurobehavior and school placement was assessed prospectively in the year 2000 in 126 children infected with HIV. PHE, developmental delay, and attention deficit disorder (ADHD) were the main outcome variables analyzed. Predictors of PHE were assessed in controlled analysis among age-matched controls. RESULTS: The rate of active PHE in 2000 was 1.6% (n = 2), and the prevalence of arrested PHE was 10% (n = 13). Residual motor and cognitive sequelae and need for special education was found in the majority of survivors. PHE relapse occurred in 3 (23%) children with previously arrested PHE. Viral load (VL) was the only significant factor associated with PHE. HIV or PHE was not associated with ADHD. Isolated developmental delay was not associated with HIV. CONCLUSIONS: PHE is an infrequent and reversible complication of HIV infection that responds to HAART and that may relapse if control of the virus is lost. Children with arrested PHE show higher rates of residual neurologic, cognitive, and scholastic impairments compared with children who never had PHE. Children with arrested PHE are the group of children with HIV infection most at risk for PHE, in the form of a relapse.

Effect of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance, and clinical manifestations of encephalopathy.

OBJECTIVES: This study evaluated the effect of treatment with abacavir/lamivudine/zidovudine versus lamivudine/zidovudine on cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA and clinical manifestations of HIV encephalopathy in children. STUDY DESIGN: HIV-infected children 7 months to 10 years of age (n = 23) were studied. CSF and plasma were obtained at baseline and weeks 8, 16, and 48. Genotype analysis of HIV was attempted at baseline and week 48. Neurologic evaluations were performed at baseline and weeks 16, 32, and 48. RESULTS: At baseline, 83% of children had >2.00 log(10) copies/mL HIV RNA in CSF, but only 10% had HIV RNA measurable at week 48. Among children in whom paired genotyping of HIV was possible, 8 of 11 had identical patterns in both CSF and plasma at baseline, whereas at week 48, only 1 of 9 children had similar patterns. Neurologic abnormalities were observed in 83% of children at baseline but only 35% of children at week 48 (P =.004), suggesting a benefit of treatment. CONCLUSIONS: Antiretroviral therapy was associated with a decline in CSF HIV RNA and an improvement in neurologic status. The development of genotypic mutations was different in CSF and plasma, suggesting discordant viral evolution. These results suggest that antiretroviral treatment in children should include agents with activity in the CNS.

[Dementia associated with AIDS]. / Demencia asociada al sida.

INTRODUCTION: Dementia associated with AIDS or AIDS dementia complex (ADC) is characterized by neurocognitive defects with disorders of the functional ability of the patient for work and the activities of everyday life. The increasing number of AIDS patients has led to a significant rise in those with neurological involvement, especially in poorer countries. DEVELOPMENT: At present no data on the incidence of ADC is available. The prevalence varies with the population studied and criteria used for diagnosis. Some authors have suggested a frequency of 8 to 16%. However, other reports mention an incidence of up to 20.7% of encephalopathy in AIDS patients. The mechanism by which ADC occurs is still not clear. Many factors have been suggested but none confirmed as causal. CLINICAL FEATURES: symptoms are due to subcortical dementia with difficulty in concentration, memory and learning whilst language, recognition, basic attention and executive function are relatively well preserved. DIAGNOSIS: this is essentially clinical, by exclusion, in cases of HIV+ patients with marked immunological deterioration and compatible clinical features. TREATMENT: current clinical guidelines recommend that most AIDS/HIV patients, if not all, should receive treatment with potent combinations of anti retroviral drugs. CONCLUSION: Even in the age of modern, highly active anti retroviral treatment, ADC is still a devastating complication of HIV infection.

[Clinical and virological correlation between the cerebrospinal fluid and blood of HIV-infected children]. / Correlación clinica y virológica entre el liquido cefalo-raquideo y la sangre de niños infectados por el HIV-1.

BACKGROUND: Although the neurological manifestations of HIV infection occur at any age, children with perinatal AIDS are affected earlier and with greater impact. There are no published data about a potential association between HIV encephalopathy and viral load in THE CSF OF the pediatric population. DESIGN: Twenty-three children, aged 7 months to 10 years, were studied as part of a multicenter international study that evaluated double versus triple antiretroviral therapy. Samples of CSF and plasma were collected for HIV RNA measurements on day 0 and on follow-up weeks 8, 16, and 48. Neurological assessments, psychological evaluations, and CT scans were done on admission and at study end. Viral isolates were processed for genotypic resistance. RESULTS: No correlation between viral load in CSF and plasma was detected at study onset. Eighty percent of children had >2 log HIV RNA in CSF at day 0 but only 30% at week 16. Eight subjects responded favorably to therapy and their CSF had undetectable viral load during follow-up determinations. On day 0, 72% of children had identical patterns of genotypic resistance in CSF and plasma samples. At week 48, however, only 11% of these subjects had identical patterns. On day 0, 83% of children had abnormal neurological findings but these alterations declined to 35% at week 48 (p = 0.004). Most children with neurological abnormalities had detectable CSF viral loads (65% vs 17%, p = 0.04). CONCLUSIONS: The data generated in this study suggest that CSF and plasma behave as two different body compartments in terms of HIV dynamics and resistance mutants. Presence of neurological abnormalities correlate with detection of HIV in CSF and these alterations improve as therapy decreases CSF viral load. These results underscore the importance of using ARV drugs with good CNS penetration for optimal management of HIV-infected young children.

Pilot study with clozapine in patients with HIV-associated psychosis and drug-induced parkinsonism.

Clozapine (CZP) is an atypical antipsychotic drug that does not appear to block striatal dopamine receptors. In six patients who met the criteria of HIV-associated psychosis and who had previously developed moderate parkinsonism as a result of the use of typical neuroleptic agents, CZP was added in an open, rising dose study. Subjects were evaluated at baseline after at least 7 days without neuroleptic drugs and then monthly for 3 months of the experimental treatment using three rating scales: Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and motor examination of the Unified Parkinson's Disease Rating Scale (UPDRS). A significant reduction in psychopathology as represented in the BPRS total score (54.2 at baseline versus 23.9 at month 3) and CGI (2 and 8, respectively) was obtained with a mean CZP dose of 27.08 mg/day. Parkinsonism also improved by an average of 76.5% at the end of the study. One patient did not complete the study as a result of a progressive decrease in leukocyte count while on CZP. These preliminary results suggest that the pharmacologic properties of CZP may be of value in the management of HIV-psychotic patients.