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In order to analyze the clinical relevance of the pharmacokinetic interactions between vinblastine and antiretrovirals described in literature, we evaluated all HIV-infected patients with Hodgkin's lymphoma treated with vinblastine-containing regimens and combination antiretroviral therapy, in a single clinical center. The use of protease inhibitors was independently associated with WHO grade III-IV neutropenia. Moreover, an inverse correlation between dosage of ritonavir and mean nadir neutrophil count was found. The concomitant administration of vinblastine-containing chemotherapy regimens with protease inhibitors can lead to higher levels of neutropenia than those of different classes of drugs such as nonnucleoside reverse transcriptase inhibitors or integrase inhibitors.

To assess the risk of clinical progression (CP) according to the duration of time spent without complete viral load (VL) suppression compared with that associated with periods of stably suppressed viremia in HIV-infected people who started highly active antiretroviral therapy (HAART) when previously naïve to antiretrovirals.A cohort study of patients having started HAART after enrollment in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA) and being followed for at least 6 months.Person-years spent in different categories according to the VL level and the change in VL from the most recent value before the initiation of HAART were calculated. A multivariable Poisson regression model, including potential confounders, was constructed.A total of 3023 patients were studied. The overall rate of CP was 13.4 per 1000 person-years. Evidence for a higher risk of CP was observed for people with a current VL10,000 copies/mL. For each year longer spent on HAART with a VL100,000 copies/mL, a 5-fold increased risk was observed (relative risk [RR] = 5.34, 95% confidence interval [CI]: 2.83 to 1.08; P = 0.0001). An increased risk of CP in patients with current suppression1.5 log10 copies/mL (RR = 2.34, 95% CI: 1.16 to 4.74; P = 0.02) and in those with no suppression or a VL higher than their set point (RR = 2.39, 95% CI: 1.17 to 4.89; P = 0.02) was observed compared with those with suppression of3 log10 copies/mL, although it was not significant. Longer duration on HAART with a VL suppressed below set point seemed to confer protection against CP.Virologic failure to antiretroviral drugs is common. The risk of CP may remain low despite a low but detectable level of HIV viremia.

Affective disorders have been reported as the most common mental health problem in persons with HIV infection. Depression has a significant impact on the quality of life of persons living with HIV and AIDS and is associated with HIV disease progression and mortality, even after controlling for sociodemographic and clinical characteristics and substance abuse. Depression has been also reported as one of the main causes of poor adherence with antiretroviral regimens. However, no published investigation has specifically focused on the relationship between depression and adherence to antiretroviral therapy. Nonetheless, information on the association between depressive symptoms and adherence may be gathered from investigations carried out to explore determinants of adherence with antiretroviral therapy. Findings from available studies show a substantial and consistent relationship between adherence to antiretroviral regimens and depression. Early recognition and proper management of depressive comorbidity could be an effective intervention strategy to improve adherence and may make a difference in the quality of life, social functioning, and disease course of people with HIV.

Objective: To establish the influence of genotypic resistance-guided treatment decisions and patient-reported adherence on the virological and immunological responses in patients failing a potent antiretroviral regimen in a randomized, controlled trial in a tertiary care infectious diseases department. Patients: A total of 174 patients with virological failure were randomly assigned to receive standard of care (SOC) or additional genotypic resistance information (G). Adherence was measured by a self-administered questionnaire. Main outcomes measures: Primary endpoints were the proportion with HIV-RNA < 500 copies/ml at 3 and 6 months by intention-to-treat analysis. Secondary endpoints were changes from baseline HIV-RNA levels and CD4 cell counts. Results: At entry, 25% had failed three or more highly active antiretroviral therapy (HAART) regimens and 41% three drug classes; there were more resistance mutations in G. In 127 evaluable questionnaires, 43% reported last missed dose during the previous week. At 3 months, 11 of 89 patients (12%) in SOC and 23 of 85 (27%) in G had HIV-RNA < 500 copies/ml (OR 2.63, 95% Cl 1.12-6.26); the relative proportions were 17 and 21% at 6 months. CD4 cell changes did not differ between arms. Six month CD4 cell changes were +62 in adherent and -13 cells/μl in non-adherent patients (P < 0.01). Being assigned to G, good adherence, previous history of virological success, fewer experienced HAART regimens and lower baseline viral load were independently predictive of 3 month virological success. Conclusion: The virological benefit of genotype-guided treatment decisions in heavily pre-exposed patients was short term. Patients adherence and residual treatment options influenced outcomes.

Objective: To alter the natural course of HIV-1 infection by inducing or potentiating immune responses to HIV-1 envelope glycoprotein. Design: Multicentre, double-blind, three-arm, placebo-controlled study. Setting: Outpatients attending clinics in two University Hospitals. Patients: Ninety-nine asymptomatic HIV-1-infected adults with CD4+ T-cell counts > 400 and < 600 x 10 6 /l and no previous antiretroviral therapy were included. Interventions: Patients were randomly assigned to three groups treated with: (i) gp160 in alum over a 2-year period in combination with placebo for the full study duration (n = 32); (ii) gp160 in alum over a 2-year period in combination with zidovudine for the full study duration (n = 34); and (iii) alum over a 2-year period in combination with zidovudine for the full study duration (n = 33). Results: Immunotherapy was well tolerated and no significant differences in disease progression were seen in the treatment groups. The majority of patients (85%) receiving gp160 showed persistent lymphoproliferative responses to the immunogen and to a different Env antigen preparation. CD4+ cell count changes in patients receiving zidovudine alone were significantly higher than those seen in patients receiving immunotherapy alone after 1 year of treatment. Zidovudine administration was associated with initial transient reduction of plasma viraemia. Conclusions: Prolonged immunization with a soluble HIV-1 subunit provided no benefit to asymptomatic HIV-1-infected patients and was inferior to zidovudine monotherapy. Furthermore, immunization with gp160 shortened the duration of the transient viral load reduction induced by zidovudine.

Article abstract-Objective: To identify disease patterns in AIDS-related focal brain lesions (FBL) and to design a decision-making strategy for differential diagnosis. Design: Prospective study. Probabilities of CNS disorders were calculated using Bayes' theorem according to clinical variables (mass effect at CT or MRI, Toxoplasma serology, anti-Toxoplasma prophylaxis) and to the results of polymerase chain reaction (PCR) assays. Patients: 136 consecutive HIV-infected patients with a definitive diagnosis of FBL-causing disorder observed from 1991 to 1995 in a single clinical setting. Interventions: Patients underwent empiric anti-Toxoplasma therapy. After 3 weeks, patients with progressive/stable disease underwent brain biopsy. In 66 patients Epstein-Barr virus (EBV)-DNA, JC virus (JCV)-DNA, and T gondii-DNA amplification was performed by PCR in CSF. Diagnostic criteria were histopathologic examination of bioptic or autoptic tissue specimens for all disorders and complete/partial resolution of FBL after empiric therapy for toxoplasmic encephalitis (TE). Results: Neuroradiologic characteristics did not discriminate between TE and primary CNS lymphoma (PCNSL). Probability of TE was 0.87 in Toxoplasma-seropositive patients with mass effect who were not receiving anti-Toxoplasma prophylaxis, but only 0.59 if prophylaxis was performed. In seronegative patients with mass effect, the likelihood of PCNSL was 0.74. If EBV-DNA or T gondii-DNA tests were positive, the probability of PCNSL or TE increased to more than 0.96. The absence of T gondii-DNA did not exclude the possibility of a TE diagnosis. Among FBL without mass effect, the probability of progressive multifocal leukoencephalopathy (PML) was 0.81; this increased to 0.99 if JCV-DNA testing was positive. Sensitivity of brain biopsy was 93%, with a perioperative morbidity of 12% and a mortality of 2%. Conclusions: Due to the low diagnostic capability of clinical variables, PCR amplifications in CSF, especially for EBV-DNA and for JCV-DNA, represent, in most cases, an essential step in the differential diagnosis of AIDS-related FBL. This is particularly true in patients with FBL without mass effect or with mass effect and who are either seronegative or undergoing anti-Toxoplasma prophylaxis. Brain biopsy remains a necessary procedure in EBV-DNA-positive cases and in seronegative patients with FBL displaying a mass effect. Positive JCV-DNA testing may obviate the need for brain biopsy in patients with FBL without mass effect. An advanced diagnostic strategy based on combined clinical criteria and PCR tests may allow rapid and accurate identification of patients for prompt brain biopsy or specific therapy.NEUROLOGY 1997;48: 687-694