Browsing by Author "Joska, John A."

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Assessing the efficacy of a modified assertive community-based treatment programme in a developing country
    (BioMed Central, 2010-09) Botha, Ulla A.; Koen, Liezl; Joska, John A.; Hering, Linda M.; Oosthuizen, Piet P.
    Background: A number of recently published randomized controlled trials conducted in developed countries have reported no advantage for assertive interventions over standard care models. One possible explanation could be that so-called “standard care” has become more comprehensive in recent years, incorporating some of the salient aspects of assertive models in its modus operandi. Our study represents the first randomised controlled trial assessing the effect of a modified assertive treatment service on readmission rates and other measures of outcome in a developing country. Methods: High frequency service users were randomized into an intervention (n = 34) and a control (n = 26) group. The control group received standard community care and the active group an assertive intervention based on a modified version of the international model of assertive community treatment. Study visits were conducted at baseline and 12 months with demographic and illness information collected at visit 1 and readmission rates documented at study end. Symptomatology and functioning were measured at both visits using the PANSS, CDSS, ESRS, WHO-QOL and SOFAS. Results: At 12 month follow-up subjects receiving the assertive intervention had significantly lower total PANSS (p = 0.02) as well as positive (p < 0.01) and general psychopathology (p = 0.01) subscales’ scores. The mean SOFAS score was also significantly higher (p = 0.02) and the mean number of psychiatric admissions significantly lower (p < 0.01) in the intervention group. Conclusions: Our results indicate that assertive interventions in a developing setting where standard community mental services are often under resourced can produce significant outcomes. Furthermore, these interventions need not be as expensive and comprehensive as international, first-world models in order to reduce inpatient days, improve psychopathology and overall levels of functioning in patients with severe mental illness.
  • Thumbnail Image
    Item
    Moderate to severe HIV-associated neurocognitive impairment : a randomized placebo-controlled trial of lithium
    (Wolters Kluwer Health, 2016-11) Decloedt, Eric H.; Freeman, Carla; Howells, Fleur; Casson-Crook, Martine; Lesosky, Maia; Koutsilieri, Eleni; Lovestone, Simon; Maartens, Gary; Joska, John A.
    Background: HIV-associated neurocognitive disorder (HAND) remains highly prevalent despite effective anti-retroviral therapy (ART). A number of adjunctive pharmacotherapies for HAND have been studied with disappointing results, but preliminary data suggest that lithium may provide clinical benefit. In addition, the low cost of lithium would facilitate access in low- and middle-income countries which carry the greatest burden of HIV. Methods: Our objective was to evaluate the 24-week efficacy and safety of lithium in patients with moderate to severe HAND. Our primary efficacy endpoint was the change in Global Deficit Score (GDS) from baseline to 24 weeks, whereas our secondary endpoint was the change in proton magnetic resonance spectroscopy (1H-MRS) brain metabolite concentrations. We conducted a 24-week randomized placebo-controlled trial of lithium as adjunctive pharmacotherapy. We enrolled participants with moderate to severe HAND, on ART for at least 6 months, with suppressed viral loads and attending public sector primary care clinics in Cape Town, South Africa. We randomized 66 participants to lithium (n = 32) or placebo (n = 34). Lithium or placebo was dosed 12-hourly and titrated to achieve the maintenance target plasma concentration of 0.6 to 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo. Results: Totally 61 participants completed the study (lithium arm = 30; placebo arm = 31). Participants at enrolment had a mean age of 40 years and a median CD4+ T-cell count of 500 cells/μL. The median change in GDS between baseline and week 24 for the lithium and placebo arms were –0.57 (95% confidence interval [CI] –0.77, –0.32) and –0.56 (–0.69, –0.34) respectively, with a mean difference of –0.054 (95% CI –0.26, 0.15); P = 0.716. The improvement remained similar when analyzed according to age, severity of impairment, CD4+ count, time on ART, and ART regimen. Standard 1H-MRS metabolite concentrations were similar between the treatment arms. The study drug was well tolerated in both study arms. Six serious adverse events occurred, but none were considered related to the study drug. Conclusion: Adjunctive lithium pharmacotherapy in patients on ART with HAND was well tolerated but had no additional benefit on neurocognitive impairment.
  • Thumbnail Image
    Item
    Peripheral blood lymphocyte proviral DNA predicts neurocognitive impairment in clade C HIV
    (Springer, 2020-07) Ruhanya, Vurayai; Jacobs, Graeme Brendon; Nyandoro, George; Paul, Robert H.; Joska, John A.; Seedat, Soraya; Glashoff, Richard Helmuth; Engelbrecht, Susan
    It is not known if proviral DNA in the periphery corresponds to cognitive status in clade C as it does in clade B and recombinant forms. A cross-sectional study was conducted on participants investigated for HIV-associated neurocognitive impairment in South Africa. HIV-1 proviral DNA was quantified using a PCR assay targeting a highly conserved HIV-1 LTR-gag region. Fifty-four (36.7%) participants were cognitively impaired and 93 (63.3%) were not impaired. Forty-three (79.6%) of the cognitively impaired participants were female and 11 (20.4%) were male. There was no significant age difference between cognitively impaired and unimpaired participants (p = 0.42). HIV-1 DNA in cognitively impaired PLWH was significantly higher than in cognitively normal individuals (p = .016). Considering impaired participants, lymphocyte HIV-1 DNA was significantly higher in males than females (p = 0.02). There was a modest positive correlation between lymphocyte HIV-1 DNA and global deficit scores (GDS) r = 0.176; p = 0.03). The two measures of viral load, lymphocyte HIV-1 DNA copies/million and plasma RNA copies/ml, were positively correlated (r = 0.39; p < .001). After adjusting for other covariates, age, sex, treatment status, and the interactions between impairment and treatment, the multivariate regression showed association between proviral load and neurocognitive impairment; omega effect size was 0.04, p value = 0.010. The burden of HIV-1 peripheral blood lymphocyte proviral DNA corresponds to neurocognitive impairment among individuals infected with clade C disease. Therefore, therapeutic strategies to reduce the HIV-1 proviral DNA reservoir in lymphocytes may improve neurocognitive outcomes in PLWH.
  • Thumbnail Image
    Item
    Renal safety of lithium in HIV-infected patients established on tenofovir disoproxil fumarate containing antiretroviral therapy : analysis from a randomized placebo-controlled trial
    (BioMed Central, 2017-02-04) Decloedt, Eric H.; Lesosky, Maia; Maartens, Gary; Joska, John A.
    Background: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. Objective: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment. Methods: We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR <60 mL/min and treated with medications predisposing to lithium toxicity. We reviewed participants weekly for the first month for adverse events followed by 4 weekly visits for renal function assessment, adverse event monitoring and adherence. Lithium dose was titrated to achieve the maintenance target plasma concentration of between 0.6 and 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo. Results: We included 23 participants allocated to the lithium arm and 30 participants allocated to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131.0 mL/min in the lithium and placebo arms respectively. There was no statistical significant difference in the reduction in eGFR or increase in potassium between the two arms during the 24 weeks. Conclusions: We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity.