Cognitive impairment among Indonesia HIV naïve patients

Background: Antiretroviral treatment (ART) can decreased the incidence of HIV dementia, but milder cognitive impairment may not resolve when patients receive ART. In Indonesia, cognitive screening of HIV patients is not routinely performed before starting ART. Here we assess cognitive impairment in ART- naïve HIV patients beginning treatment in Jakarta. Methods: This is a cross sectional study with inclusion criteria: HIV positive, ART naïve, CD4 T-cells below 200 cells/uL, Karnofsky Performance Score (KPS) above 70. HIV-associated neurocognitive disorder (HAND) was defined by performance at least 1 Standard Deviation (SD) below the mean of demographically adjusted normative scores in at least two cognitive areas. Results: We studied 82 subjects with median (range) age 31 (19-48) years. Fifty six subjects (68%) were males. HAND was found in 42 subjects (51%). Eight subjects (19%) had impairment in 4 domains, 15 subjects (36%) in 3 and 19 (45%) in 2. The most common domain affected was memory (63%). Conclusion: Our results show the prevalence of HAND is high among HIV naïve patients in Jakarta. This establishes the need for screening of cognitive function before initiating ART

Neuropathic pain in HIV patients receiving ART without stavudine in an Indonesia Referral Hospital

Lower limb neuropathic pain in HIV patients is a common manifestation of sensory neuropathy (HIV-SN), but can be seen in patients who do not meet standard definitions of HIV-SN. The drug stavudine is a risk factor for HIV-SN, but some patients treated without stavudine experience HIV-SN, and the prevalence and risk factors influencing neuropathic pain in this setting are unknown. A cross sectional study at Cipto Mangunkusumo Hospital Jakarta tested 197 HIV patients treated for >12 months without stavudine. HIV-SN was defined using the AIDS Clinical Trial Group Brief Peripheral Neuropathy Screening Test (ACTG-BPNST). A validated Indonesia translation of Douleur Neuropathique en 4 (DN4) questionnaire was used to assess lower limb neuropathic pain. Nerve conduction studies assessed large nerve fiber function and Stimulated Skin Wrinkle (SSW) tests were performed to assess small nerve fibers. The prevalence of neuropathic pain was 6.6%. BPNST + HIV-SN was diagnosed in 14.2% of the cohort and 38.5% of patients with pain. Use of protease inhibitors and ART duration <2 years associated with neuropathic pain in univariate (p =.036, p =.002, resp.) and multivariable analyses (model p <.001). SSW tests were abnormal in 53.8% of subjects with neuropathic pain and only 25.5% without pain (p =.05). Patients with pain without BPNST + HIV-SN had begun ART more recently than those with both diagnoses. Overall this preliminary study showed that neuropathic pain associated with protease inhibitors and a shorter duration of ART in Indonesian HIV patients, and may be an early symptom of small fiber neuropathy in this context

High dose oral rifampicin to improve survival from adult tuberculous meningitis: A randomised placebo-controlled double-blinded phase III trial (the HARVEST study)

Background: Tuberculous meningitis (TBM), the most severe form of tuberculosis (TB), results in death or neurological disability in >50%, despite World Health Organisation recommended therapy. Current TBM regimen dosages are based on data from pulmonary TB alone. Evidence from recent phase II pharmacokinetic studies suggests that high dose rifampicin (R) administered intravenously or orally enhances central nervous system penetration and may reduce TBM associated mortality. We hypothesize that, among persons with TBM, high dose oral rifampicin (35 mg/kg) for 8 weeks will improve survival compared to standard of care (10 mg/kg), without excess adverse events. Protocol: We will perform a parallel group, randomised, placebo-controlled, double blind, phase III multicentre clinical trial comparing high dose oral rifampicin to standard of care. The trial will be conducted across five clinical sites in Uganda, South Africa and Indonesia. Participants are HIV-positive or negative adults with clinically suspected TBM, who will be randomised (1:1) to one of two arms: 35 mg/kg oral rifampicin daily for 8 weeks (in combination with standard dose isoniazid [H], pyrazinamide [Z] and ethambutol [E]) or standard of care (oral HRZE, containing 10 mg/kg/day rifampicin). The primary end-point is 6-month survival. Secondary end points are: i) 12-month survival ii) functional and neurocognitive outcomes and iii) safety and tolerability. Tertiary outcomes are: i) pharmacokinetic outcomes and ii) cost-effectiveness of the intervention. We will enrol 500 participants over 2.5 years, with follow-up continuing until 12 months post-enrolment. Discussion: Our best TBM treatment still results in unacceptably high mortality and morbidity. Strong evidence supports the increased cerebrospinal fluid penetration of high dose rifampicin, however conclusive evidence regarding survival benefit is lacking. This study will answer the important question of whether high dose oral rifampicin conveys a survival benefit in TBM in HIV-positive and -negative individuals from Africa and Asia. Trial registration: ISRCTN15668391 (17/06/2019

Sklerosis Multipel

Sklerosis Multipel (MS) adalah penyakit autoimun yang terutama menyerang perempuan usia muda, tergolong penyakit langka di Indonesia. Meskipun demikian, penyakit ini dapat mengakibatkan kecacatan dan menurunkan kualitas hidup. Penegakan diagnosis yang akurat sangat diperlukan agar pasien MS bisa mendapatkan pengobatan yang adekuat sedini mungkin. Tata laksana pasien MS perlu memperhatikan tipe MS dan gejala yang menyertai.Multiple sclerosis (MS) is an autoimmune disease that mostly affected young women; this disease is rare in Indonesia. Nevertheless, MS can result in severe disability and decreased quality of life. Accurate diagnosis is needed as early as possible to initiate proper treatment. In MS management it is important to classify the disease and also treat the accompanying symptoms

Diagnosis dan Tatalaksana Meningitis Bakterialis

Meningitis bakterialis (MB) adalah kegawatdaruratan neurologik yang mengancam jiwa dan memerlukan diagnosis serta terapi yang cepat. Penanganan MB memerlukan pendekatan interdisipliner. Penegakan diagnosis MB kadang sulit jika hanya mengandalkan anamnesis dan pemeriksaan fisik. Hasil pemeriksaan cairan serebrospinal (CSS) harus diinterpretasikan secara hati-hati. Pemahaman karakter pasien sangat dibutuhkan untuk memberikan antibiotik empirik yang tepat.Bacterial meningitis is a life-threatening neurologic emergency that needs rapid diagnosis and treatment. Management of bacterial meningitis needs interdisciplinary approach. The diagnosis of bacterial meningitis can sometimes be difficult when relying only on history and physical examination. Cerebrospinal fluid (CSF) examination results must be interpreted carefully. To provide appropriate empiric antibiotics therapy, understanding of patient's characteristic is essential

HIV patients, healthy aging and transplant recipients can reveal the hidden footprints of CMV.

Cytomegalovirus (CMV) is a β-herpesvirus. Latent infections are common in all populations. However age-associated increases in levels of CMV-reactive antibody are testament to repeated reactivations and periods of viral replication. CMV has been associated with several diseases of aging, including vasculopathy and neurocognitive impairment. These conditions occur at a younger age in persons with particularly high burdens of CMV - transplant recipients and people living with HIV. Here we define the “clinical footprints” as immunopathologies triggered by CMV that develop over many years. A high burden of CMV also drives accumulation of multifunctional terminally-differentiated αβ T-cells, a novel population of Vδ2 − γδ T-cells, and a population of CD56lo NK cells lacking a key regulatory molecule. An understanding of these “immunological footprints” of CMV may reveal how they collectively promote the “clinical footprints” of the virus. This is explored here in transplant recipients, HIV patients and healthy aging

Polymorphisms in IL10 may alter CD4 T-cell counts in Indonesian HIV patients beginning antiretroviral therapy

Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine influenced by single nucleotide polymorphisms (SNP) located in upstream regulatory regions. Here we address the effects of five SNP (rs1518111, rs3021094, rs3024491, rs1800872 and rs1800871) on CD4 T-cell counts in Indonesian HIV patients assessed before ART and over 12 months on treatment. Heterozygosity at rs1518111 or rs1800872 associated with low CD4 T-cell counts at all time points. Both alleles were carried in two haplotypes. Haplotype 21122 (present in 30% of participants) associated with low CD4 T-cell counts, whereas 21222 (in 6% of participants) did not. Hence untyped SNP(s) tagged by 21122 may depress CD4 T-cell counts. The association with heterozygosity suggests synergy with an allele from a haplotype lacking rs1518111 and/or rs1800872