Browsing by Subject "CD4 Lymphocyte Count"

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    Open Access
    Diagnosing tuberculosis in hospitalized HIV-infected individuals who cannot produce sputum: is urine lipoarabinomannan testing the answer?
    (2017) Sabur, Natasha F; Esmail, Aliasgar; Brar, Mantaj S; Dheda, Keertan
    Abstract Background Up to one third of HIV-infected individuals with suspected TB are sputum-scarce. The Alere Determine™ TB LAM Ag lateral flow strip test can be used to diagnose TB in HIV-infected patients with advanced immunosuppression. However, how urine LAM testing should be incorporated into testing algorithms and in the context of specific patient sub-groups remains unclear. Methods This study represents a post hoc sub-group analysis of data from a randomized multi-center parent study. The study population consisted of hospitalized HIV-infected patients with suspected TB who were unable to produce sputum and who underwent urine LAM testing. The diagnostic utility of urine LAM for TB in this group was compared to the performance of urine LAM in patients who did produce a sputum sample in the parent study. Results There were a total of 187 and 2341 patients in the sputum-scarce and sputum-producing cohorts, respectively. 80 of the sputum-scarce patients underwent testing with urine LAM. In comparison to those who did produce sputum, sputum-scarce patients had a younger age, a lower Karnofsky performance score, and a lower weight and BMI at admission. A greater proportion of sputum-scarce patients were urine LAM positive, compared to those who were able to produce sputum (31% vs. 21%, p = 0.04). A higher proportion of sputum-scarce patients died within 8 weeks of admission (32% vs. 24%, p = 0.013). We inferred that 19% of HIV-infected sputum-scarce patients suspected of TB were diagnosed with tuberculosis by urine LAM testing, with an estimated positive predictive value of 63% (95% CI 43–82%). Conclusions Urine LAM testing can effectively identify tuberculosis in HIV-infected patients who are at a higher risk of mortality yet are unable to generate a sputum sample for diagnostic testing. Our findings support the use of urine LAM testing in sputum-scarce hospitalized HIV-infected patients, and its incorporation into diagnostic algorithms for this patient population.
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    HIV viral load as an independent risk factor for tuberculosis in South Africa: collaborative analysis of cohort studies
    (2017) Fenner, Lukas; Atkinson, Andrew; Boulle, Andrew; Fox, Matthew P; Prozesky, Hans; ZYrcher, Kathrin; Ballif, Marie; Furrer, Hansjakob; Zwahlen, Marcel; Davies, Mary-Ann; Egger, Matthias
    Introduction: Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART).
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    Prolonged deferral of antiretroviral therapy in the SAPIT trial: Did we need a clinical trial to tell us that this would increase mortality?
    (2010) Boulle, Andrew; Clayden, Polly; Cohen, Karen; Cohen, Ted; Conradie, Francesca; Dong, Christa; Geffen, Nathan; Grimwood, Ashraf; Hurtado, Rocio; Kenyon, Christopher; Lawn, Stephen; Maartens, Gary; Meintjes, Graeme; Mendelson, Marc; Murray, Megan; Rangaka, Molebogeng; Sanne, Ian; Spencer, David; Taljaard, Jantjie; Variava, Ebrahim; Venter, W D Francois; Wilson, Douglas
    Tuberculosis is the major cause of morbidity and mortality in HIVinfected patients in sub-Saharan Africa. HIV infection is often first diagnosed following a diagnosis of tuberculosis, with many patients needing antiretroviral therapy (ART). Starting ART in HIV-infected patients with tuberculosis (TB) may be associated with complications, including side-effects from co-administration of multiple drugs with many overlapping toxicities, reductions in concentrations of certain antiretroviral drugs following the induction of metabolising enzymes and drug transporters by rifampicin, and paradoxical deterioration due to the immune reconstitution inflammatory syndrome (IRIS). Furthermore, the high pill burden of co-treatment could reduce adherence, resulting in poor treatment outcomes for both diseases. These potential harms must be weighed against the high mortality rates in patients with HIV-associated tuberculosis who do not receive ART, especially those with low CD4 counts. The optimal time to initiate ART in patients with tuberculosis is an important research question, and randomised controlled trials are addressing this issue.
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    Risk factors for unstructured treatment interruptions and association with survival in low to middle income countries
    (2016) McMahon, James H; Spelman, Tim; Ford, Nathan; Greig, Jane; Mesic, Anita; Ssonko, Charles; Casas, Esther C; O’Brien, Daniel P
    Abstract Background Antiretroviral therapy (ART) treatment interruptions lead to poor clinical outcomes with unplanned or unstructured TIs (uTIs) likely to be underreported. This study describes; uTIs, their risk factors and association with survival. Methods Analysis of ART programmatic data from 11 countries across Asia and Africa between 2003 and 2013 where an uTI was defined as a ≥90-day patient initiated break from ART calculated from the last day the previous ART prescription would have run out until the date of the next ART prescription. Factors predicting uTI were assessed with a conditional risk-set multiple failure time-to-event model to account for repeated events per subject. Association between uTI and mortality was assessed using Cox proportional hazards, with a competing risks extension to test for the influence of lost to follow-up (LTFU). Results 40,632 patients were included from 11 countries across 33 sites (17 Africa, 16 Asia). Median duration of follow-up was 1.61 years (IQR 0.54–3.31 years), 3386 (8.3 %) patients died, and 3453 (8.5 %) were LTFU. There were 14,817 uTIs, with 10,162 (25 %) patients having more than one uTI. In the adjusted model males were at lower risk of uTI (aHR 0.94, p < 0.01, and age 20–59 was protective compared to <20 years (20–39 years aHR 0.87, p < 0.01; 40–59 years aHR 0.86, p < 0.01). Preserved immune function, as measured by higher CD4 cell count, was associated with a reduced rate of uTI compared to CD4 <200 cells/μL (CD4 200–350 cells/μL aHR 0.89, p < 0.01; CD4 >350 cells/μL aHR 0.87, p < 0.01), whereas advanced clinical disease was associated with increased uTI rate (WHO stage 3 aHR 1.10, p < 0.01; WHO stage 4 aHR 1.21, p < 0.01). There was no relationship between uTI and mortality after adjusting for disease status and considering LTFU as a competing risk. Conclusions uTIs were frequent in people in ART programs in low-middle income countries and associated with younger age, female gender and advanced HIV. uTI did not predict survival when loss to follow-up was considered a competing risk. Further evaluation of uTI predictors and interventions to reduce their occurrence is warranted.
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    Sensory neuropathy and metabolic risk factors in human immune deficiency virus infected South Africans receiving protease inhibitors
    (2015) Vermaak, John-Randel; Dave, Joel A; Levitt, Naomi; Heckmann, Jeannine M
    BackgroundProtease inhibitors (PI)s have been associated with distal sensory polyneuropathy (DSP) and metabolic complications in high-income countries. No data exist in Africans where second-line antiretroviral therapy (ART) often include PIs.MethodWe performed a cross-sectional study to assess the DSP frequency and metabolic risk factors in community-based South Africans taking ritonavir-boosted lopinavir as PI. Examination findings categorized subjects as having DSP (≥1 neuropathic sign) or symptomatic DSP [DSP with symptom(s)]. Fasting-state glucose and lipid profiles were assessed. We compared the ritonavir/lopinavir-group to a nested group on first-line ART [dideoxy-nucleoside reverse transcriptase inhibitors (d-drugs)] selected from a dataset collected at the same time and matched for d-drug exposure.ResultsThe ritonavir/lopinavir-group (n=86) consisted predominantly of women (84%) with a median age of 36years (IQR 32–41). The median current CD4+ count was 489cells/μL (IQR 291–665). The median exposure time to ritonavir/lopinavir was 18months (IQR 10–26) and to d-drugs, 24months (IQR 16–38). DSP was present in 78% and symptomatic DSP in 48%; symptoms were most frequently of moderate intensity. Only age independently associated with DSP and symptomatic DSP (p=0.08 and p=0.04, respectively). None of the metabolic syndrome components showed associations with DSP or symptomatic DSP despite a trend towards hypertriglyceridemia overall. The ritonavir/lopinavir-group had less DSP compared to the d-drug only group (p=0.002) but the frequency of symptomatic DSP was similar (p=0.49).ConclusionRitonavir-boosted lopinavir did not add additional risk to developing DSP in this community-based African cohort after a median of 18months on second-line ART.Electronic supplementary materialThe online version of this article (doi:10.1186/s12981-015-0073-8) contains supplementary material, which is available to authorized users.
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    Severe adverse events during second-line tuberculosis treatment in the context of high HIV Co-infection in South Africa: a retrospective cohort study
    (2016) Schnippel, Kathryn; Berhanu, Rebecca H; Black, Andrew; Firnhaber, Cynthia; Maitisa, Norah; Evans, Denise; Sinanovic, Edina
    Abstract Background According to the World Health Organization, South Africa ranks as one of the highest burden of TB, TB/HIV co-infection, and drug-resistant TB (DR-TB) countries. DR-TB treatment is complicated to administer and relies on the use of multiple toxic drugs, with potential for severe adverse drug reactions. We report the occurrence of adverse events (AEs) during a standardised DR-TB treatment regimen at two outpatient, decentralized, public-sector sites in Johannesburg, South Africa. Methods We reviewed medical records of the six-month intensive treatment phase for rifampicin-resistant (RR) TB patients registered May 2012 - December 2014. Patients contributed follow-up time until death, loss from treatment, censoring (6 months) or data extraction. A standardized regimen of kanamycin, moxifloxacin, ethionamide, terizidone, and pyrazinamide was used according to national guidelines. AEs were graded using the AIDS Clinical Trial Group scale. We present subhazard ratios from competing risk analysis for time to severe AE, accounting for mortality and loss from treatment. Results Across the two sites, 578 eligible patient files were reviewed. 36.7 % were categorized as low weight (≤50 kg) at DR-TB initiation. 76.0 % had no history of TB treatment prior to the current episode of RR TB. 26.8 % were diagnosed with RR TB while hospitalized, indicating poor clinical condition. 82.5 % of patients were also HIV positive, of whom 43.8 % were on ART prior to RR TB treatment and 32.1 % initiated ART with or after RR TB treatment. Median CD4 count was 114.5 (IQR: 45-246.5). Overall, 578 reports of AEs were captured for 204 patients (35.3 %) and 110 patients (19.0 %) had at least one severe AE reported. Patients with at least one AE experienced a median of 3 (IQR: 2-4) AEs per patient. HIV-positive patients with CD4 counts ≤100 cells/mm 3 and those newly initiating ART were more likely to experience a severe AE (sHR: 2.76, 95 % CI: 1.30–5.84 and sHR: 3.07, 95 % CI: 1.46–6.46, respectively). Conclusion Severe AE are common during the first 6 months of RR TB treatment and HIV-positive patients newly initiating ART have the highest subdistribution hazard ratio for severe AE, accounting for the competing risks of death and loss from treatment.
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    Where do HIV-infected adolescents go after transfer? – Tracking transition/transfer of HIV-infected adolescents using linkage of cohort data to a health information system platform
    (2017) Davies, Mary-Ann; Tsondai, Priscilla; Tiffin, Nicki; Eley, Brian; Rabie, Helena; Euvrard, Jonathan; Orrell, Catherine; Prozesky, Hans; Wood, Robin; Cogill, Dolphina; Haas, Andreas D; Sohn, Annette H; Boulle, Andrew
    Introduction: To evaluate long-term outcomes in HIV-infected adolescents, it is important to identify ways of tracking outcomes after transfer to a different health facility. The Department of Health (DoH) in the Western Cape Province (WCP) of South Africa uses a single unique identifier for all patients across the health service platform. We examined adolescent outcomes after transfer by linking data from four International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) cohorts in the WCP with DoH data.