Management of HIV-associated cryptococcal disease in South Africa

Govender, Nelesh P.; Dlamini, Sipho

doi:10.7196/samj.9070

Cited by 12 publications

(11 citation statements)

References 31 publications

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“…Current guidelines in South Africa for preemptive care of identified CrAg positive patients are 800mg of fluconazole for 2 weeks prior to the initiation of ART, followed by initiation of ART and continuation of daily fluconazole, 400mg for 8 weeks and then 200mg daily for at least 1 year until CD4 counts are > 200 cells/μl. [ 13 , 27 ] The details vary slightly depending on if the patient has symptoms relevant to CM and if the patient receives a lumbar puncture for further diagnosis.…”

Section: Methodsmentioning

confidence: 99%

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa

et al. 2016

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BackgroundIn 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ μl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies.MethodsWe developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions.ResultsIn the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment).ConclusionsIn countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved.

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Section: Methodsmentioning

confidence: 99%

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa

et al. 2016

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“…Despite the availability of antiretroviral therapy (ART) in South Africa, approximately 10% of HIV-infected patients still present to care with a CD4 count <100 cells/μl [ 8 ]. Patients with advanced HIV disease, defined as CD4<200cells/μl as per World Health Organization (WHO) guidelines, are more vulnerable to CM which is associated with high mortality rates even with efficacious and prompt antifungal therapy [ 6 ]. While early diagnosis of HIV infection and initiation of ART prior to the development of AIDS is critical to reduction of CM incidence, a cryptococcal antigen (CrAg) screen-and-treat intervention has the potential to reduce cryptococcal disease-related mortality by identifying patients prior to onset of CM [ 6 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Cryptococcal antigen positivity combined with the percentage of HIV-seropositive samples with CD4 counts <100 cells/μl identifies districts in South Africa with advanced burden of disease

et al. 2018

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IntroductionCryptococcal meningitis (CM) is an opportunistic fungal disease with a high mortality among HIV-positive patients with severe immunosuppression (CD4 count <100 cells/μl). Reflexed screening for cryptococcal antigen (CrAg) in remnant blood samples was initially piloted at selected CD4 testing laboratories of the National Health Laboratory Service (NHLS) prior to the implementation of a national screening programme using a lateral flow assay (LFA) (IMMY, Norman, OK, USA). The aim of this study was to assess CrAg positivity nationally, per province and district in combination with the percentage of CD4 samples tested with a CD4 count <100 cells/μl to identify areas with advanced HIV/CrAg disease burden.MethodsCrAg and CD4 laboratory result data were extracted from the NHLS corporate data warehouse. Monthly test volumes were used to assess CrAg test volumes and coverage, while bubble charts were used to display the relationship between CD4 <100 cells/μl, CrAg positivity and number of positive CrAg samples by district. ArcGIS software was used to spatially report CrAg positivity.ResultsCrAg screening coverage was stable at around 96% after November 2016. Samples with a CD4 <100 cell/μl and CrAg positivity were also stable over the study period at 10% and ~5% respectively. The highest CrAg positivity was reported for the Kwa-Zulu Natal province (7.3%), which also had the lowest percentage of samples with a CD4 <100 cells/μl (7.2%). Uthungulu and Umkhanyakude districts had the highest CrAg positivity (9.3% and 8.9% respectively). Ethekwini and Johannesburg Metro districts contributed to 22% of the total number of CrAg-positive samples tested across South Africa for the period reported.ConclusionExisting CD4 testing services were used to rapidly scale up CrAg reflex testing in South Africa. Districts with advanced HIV and CrAg disease burden were identified that need further investigation of patient management interventions.

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“…The initial (induction phase) management of HIV/CCM requires the following: (1) combination antifungal therapy including IV amphotericin B and oral flucytosine (first week only) and high-dose oral fluconazole 1200 mg daily (second week), after that an 8-week consolidation phase of oral fluconazole 800 mg daily, (2) control of raised intracranial pressure (rIP) with therapeutic lumbar punctures (LPs) to maintain the ‘opening-pressure’ (CSF-OP) at < 25 cm of water and (3) minimising the risk of immune reconstitution inflammatory syndrome (IRIS) by delaying the initiation of ART until 4 to 6 weeks after the start of antifungal therapy. 8 , 9 , 10 , 11 , 12 …”

Section: Introductionmentioning

confidence: 99%

Intracranial pressure management in patients with human immunodeficiency virus-associated cryptococcal meningitis in a resource-constrained setting

Mkoko

Preez

Naidoo

2020

Southern African Journal of HIV Medicine

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Background Cryptococcal meningitis (CCM) is the leading cause of meningitis in people living with HIV (PLWH) in sub-Saharan Africa (SSA). The mortality and morbidity associated with CCM remain high. Combination of antifungal therapy, diligent management of intracranial pressure (IP) and the correct timing of the introduction of antiretroviral therapy (ART) minimise the risk of mortality and morbidity. The absence of spinal manometers in many healthcare centres in SSA challenges the accurate measurement of cerebrospinal fluid (CSF) pressure and its control. Objectives We hypothesised that four lumbar punctures (LPs) in the first week of the diagnosis and treatment of CCM would reduce IP such that in-hospital mortality and morbidity of HIV-associated CCM (HIV/CCM) would be significantly reduced. Methods We conducted a retrospective study to assess whether receipt of four or more LPs in the first week of the diagnosis and treatment with combination antifungal therapy of HIV/CCM would be associated with the reduction of in-hospital mortality in adult PLWH. Results From 01 January 2016 to 31 December 2016, 116 adult patients were admitted to the Dora Nginza District Hospital in Zwide, Port Elizabeth, South Africa. After exclusion of 11 (two were younger than 18 years, two had missing hospital records and seven demised or left the hospital before 7 days of hospitalisation), 105 patients were included in the analysis. The mean age was 39.4 (standard deviation [s.d.] ± 9.7) years, 64.8% were male. All were PLWH. A total of 52.4% had defaulted ART and 25.7% were ART naïve. Forty-three patients received four or more LPs (mean = 4.58 [± 0.96]) in the first week of hospitalisation with an associated in-hospital mortality of 11.6% ( n = 5/43) compared with 62 patients who received less than four LPs (mean = 2.18 [± 0.80]) with an in-hospital mortality of 29% ( n = 18/62) and a relative risk of 0.80 (95% CI, 0.66–0.97), p = 0.034. Conclusion In the current study of adult PLWH presenting to hospital with HIV/CCM, four or more LPs in the first 7 days following admission and the initiation of treatment were associated with a 17.4% reduction in absolute risk of in-hospital mortality and a 20% reduction in relative risk of in-hospital mortality. This mortality difference was noted in patients who survived and were in hospital at the time of the 7-day study census and persisted until the time of hospital discharge.

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Management of HIV-associated cryptococcal disease in South Africa

Cited by 12 publications

References 31 publications

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa

Cryptococcal antigen positivity combined with the percentage of HIV-seropositive samples with CD4 counts <100 cells/μl identifies districts in South Africa with advanced burden of disease

Intracranial pressure management in patients with human immunodeficiency virus-associated cryptococcal meningitis in a resource-constrained setting

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