Browsing by Author "Rebe, Kevin"

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    Clinical and financial burdens of secondary level care in a public sector antiretroviral roll-out setting (G F Jooste Hospital)
    (Academy of Science of South Africa, 2009) Kevany, Sebastian; Meintjes, Graeme; Rebe, Kevin; Maartens, Gary; Cleary, Susan
    Background: Antiretroviral therapy (ART) is being extended across South Africa. While efforts have been made to assess the costs of providing ART via accredited service points, little information is available on its downstream costs, particularly in public secondary level hospitals. Objectives: To determine the cost of care for inpatients and outpatients at a dedicated antiretroviral referral unit treating and caring for antiretroviral-related conditions in a South African peri-urban setting; to identify key epidemiological cost drivers; and to examine the associated clinical and outcome data. Methods: A prospective costing study on 48 outpatients and 25 inpatients was conducted from a health system perspective. Incremental economic costs and clinical data were collected from primary sources at G F Jooste Hospital, Cape Town, over a 1-month period (March 2005). Results: Incremental cost per outpatient was R1 280, and per inpatient R5 802. Costs were dominated by medical staff costs (62% inpatient and 58% outpatient, respectively). Infections predominated among diagnoses and costs – 55% and 67% respectively for inpatients, and 49% and 54% respectively for outpatients. Most inpatients and outpatients were judged by attending physicians to have improved or stabilised as a result of treatment (52% and 59% respectively). Conclusions. The costs of providing secondary level care for patients on or immediately preceding ART initiation can be significant and should be included in the government’s strategic planning: (i) so that the service can be expanded to meet current and future needs; and (ii) to avoid crowding out other secondary level health services.
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    Clinical deterioration during antitubercular treatment at a district hospital in South Africa: the importance of drug resistance and AIDS defining illnesses
    (Public Library of Science, 2009) Pepper, Dominique J; Rebe, Kevin; Morroni, Chelsea; Wilkinson, Robert J; Meintjes, Graeme
    BACKGROUND: Clinical deterioration on drug therapy for tuberculosis is a common cause of hospital admission in Africa. Potential causes for clinical deterioration in settings of high HIV-1 prevalence include drug resistant Mycobacterium tuberculosis (M.tb) , co-morbid illnesses, poor adherence to therapy, tuberculosis associated-immune reconstitution inflammatory syndrome (TB-IRIS) and subtherapeutic antitubercular drug levels. It is important to derive a rapid diagnostic work-up to determine the cause of clinical deterioration as well as specific management to prevent further clinical deterioration and death. We undertook this study among tuberculosis (TB) patients referred to an adult district level hospital situated in a high HIV-1 prevalence setting to determine the frequency, reasons and outcome for such clinical deterioration. Method A prospective observational study conducted during the first quarter of 2007. We defined clinical deterioration as clinical worsening or failure to stabilise after 14 or more days of antitubercular treatment, resulting in hospital referral. We collected data on tuberculosis diagnosis and treatment, HIV-1 status and antiretroviral treatment, and investigated reasons for clinical deterioration as well as outcome. RESULTS: During this period, 352 TB patients met inclusion criteria; 296 were admitted to hospital accounting for 17% of total medical admissions (n = 1755). Eighty three percent of TB patients (291/352) were known to be HIV-1 co-infected with a median CD4 count of 89cells/mm 3 (IQR 38-157). Mortality among TB patients admitted to hospital was 16% (n = 48). The median duration of hospital admission was 9.5 days (IQR 4-18), longer than routine in this setting (4 days). Among patients in whom HIV-1 status was known (n = 324), 72% of TB patients (n = 232) had an additional illness to tuberculosis; new AIDS defining illnesses (n = 80) were the most frequent additional illnesses (n = 208) in HIV-1 co-infected patients (n = 291). Rifampin-resistant M.tb (n = 41), TB-IRIS (n = 51) and drug resistant bacterial infections (n = 12) were found in 12%, 14% and 3.4% of the 352 cases, respectively. Interpretation In our setting, new AIDS defining illnesses, drug resistant M.tb and other drug resistant bacteria are important reasons for clinical deterioration in HIV-1 co-infected patients receiving antitubercular treatment. HIV-1 co-infected patients may be at increased risk of acquiring nosocomial drug resistant pathogens because profound immune suppression results in co-morbid illnesses that require prolonged inpatient admissions. Routine infection control is essential and needs to be strengthened in our setting.
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    Comparison of an in-house real-time duplex PCR assay with commercial HOLOGIC® APTIMA assays for the detection of Neisseria gonorrhoeae and Chlamydia trachomatis in urine and extra-genital specimens
    (2019-01-03) Venter, Johanna M E; Mahlangu, Precious M; Müller, Etienne E; Lewis, David A; Rebe, Kevin; Struthers, Helen; McIntyre, James; Kularatne, Ranmini S
    Abstract Background Extra-genital Neisseria gonorrhoeae and Chlamydia trachomatis infections are mostly asymptomatic, and important reservoir sites of infection as they often go undetected and may be more difficult to eradicate with recommended therapeutic regimens. Commercial nucleic acid amplification tests (NAATs) have not received regulatory approval for the detection of N. gonorrhoeae and C. trachomatis in extra-genital specimens. The HOLOGIC® APTIMA Combo2 assay for N. gonorrhoeae and C. trachomatis has performed well in evaluations using extra-genital specimens. Methods We assessed the performance of an in-house real-time duplex PCR assay for the detection of N. gonorrhoeae and C. trachomatis in urine and extra-genital specimens using the HOLOGIC® APTIMA assays as gold standard comparators. Urine, oropharyngeal and ano-rectal specimens were collected from each of 200 men-who-have-sex-with-men (MSM) between December 2011 and July 2012. Results For N. gonorrhoeae detection, the in-house PCR assay showed 98.5–100% correlation agreement with the APTIMA assays, depending on specimen type. Sensitivity for N. gonorrhoeae detection was 82.4% for ano-rectal specimens, 83.3% for oropharyngeal specimens, and 85.7% for urine; and specificity was 100% with all specimen types. The positive predictive value (PPV) for N. gonorrhoeae detection was 100% and the negative predictive value (NPV) varied with sample type, ranging from 98.5–99.5%. For C. trachomatis detection, correlation between the assays was 100% for all specimen types. The sensitivity, specificity, PPV and NPV of the in-house PCR assay was 100% for C. trachomatis detection, irrespective of specimen type. Conclusion The in-house duplex real-time PCR assay showed acceptable performance characteristics in comparison with the APTIMA® assays for the detection of extra-genital N. gonorrhoeae and C. trachomatis.
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    Cost effectiveness analysis of two alternative interventions for the integration of Tenofovir into South Africa's public sector First Line Antiretroviral treatment regimen
    (2009) Lin, Iming; Cleary, Susan; Meintjies, Graeme; Rebe, Kevin
    In 2003, South Africa's National Department of Health (DoH) initiated the roll out of antiretroviral therapy (ART) for HIV positive individuals in the public health sector. Based on World Health Organization (WHO) guidelines, South Africa's ART programme provides a first line regimen based on a backbone of two nucleoside reverse transcriptase enzyme inhibitors (NRTI) with one non-nucleoside reverse transcriptase inhibitor (NNRTI) while the second line regimen is based on a protease inhibitor (PI) with two NRTIs. Similar to many developing countries, South Africa's NRTI backbone in the first line treatment regimen is stavudine (d4T) combined with lamivudine (3TC), and the NNRTI which is either efavirenz (EFV) or nevirapine (NVP). In some cases, stavudine is replaced with the NRTI zidovudine (AZT) in the first line regimen. Both d4T and AZT have been recognized to contribute to drug related toxicities or side effects, particularly lactic acidosis, lypodystrophy, peripheral neuropathy, and anaemia. However, developing country governments have been limited to these NRTI choices due to the higher cost of alternative treatment options. There is compelling logic that the life long commitment of ART can be made more tolerable, and that adherence among patients and the success of a public sector ART programme can be increased through the provision of ART regimens with the fewest side effects. In addition, the costs and complications associated with treating and managing adverse events associated with d4T and AZT create further burden on the public health sector. By providing tenofovir as an alternative to d4T and AZT in first line ART therapy, the South African government would increase the chance of successful ART therapy for patients and the long-term success of the national ART programme. This cost effectiveness analysis will compare the currently available first line ART options (the status quo) to two alternative options in order to assess the costeffectiveness of the provision of tenofovir in place of d4T/AZT.
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    A cross sectional analysis of Gonococcal and Chlamydial infections among men-who-have-sex-with-men in Cape Town, South Africa
    (Public Library of Science, 2015) Rebe, Kevin; Lewis, David; Myer, Landon; de Swardt, Glenn; Struthers, Helen; Kamkuemah, Monika; McIntyre, James
    BACKGROUND: Men-who-have-sex-with-men (MSM) are at high risk of HIV and sexually transmitted infection (STI) transmission. Asymptomatic STIs are common in MSM and remain undiagnosed and untreated where syndromic management is advocated. Untreated STIs could be contributing to high HIV rates. This study investigated symptomatic (SSTI) and asymptomatic STIs (ASTIs) in MSM in Cape Town. METHODS: MSM, 18 years and above, were enrolled into this study. Participants underwent clinical and microbiological screening for STIs. Urine, oro-pharyngeal and anal swab specimens were collected for STI analysis, and blood for HIV and syphilis screening. A psychosocial and sexual questionnaire was completed. STI specimens were analysed for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infection. RESULTS: 200 MSM were recruited with a median age of 32 years (IQR 26-39.5). Their median number of sex partners within the last year was 5 (IQR 2-20). 155/200 (78%) reported only male sex partners while 45/200 (23%) reported sex with men and women. 77/200 (39%) reported transactional sex. At enrolment, 88/200 (44%) were HIV positive and 8/112 (7%) initially HIV-negative participants seroconverted during the study. Overall, 47/200 (24%) screened positive for either NG or CT. There were 32 MSM (16%) infected with NG and 7 (3.5%) of these men had NG infections at two anatomical sites (39 NG positive results in total). Likewise, there were 23 MSM (12%) infected with CT and all these men had infections at only one site. Eight of the 47 men (17%) were infected with both NG and CT. ASTI was more common than SSTI irrespective of anatomical site, 38 /200 (19%) versus 9/200 (5%) respectively (p<0.001). The anus was most commonly affected, followed by the oro-pharynx and then urethra. Asymptomatic infection was associated with transgender identity (OR 4.09 CI 1.60-5.62), ≥5 male sex partners in the last year (OR 2.50 CI 1.16-5.62) and transactional sex (OR 2.33 CI 1.13-4.79) but not with HIV infection. CONCLUSIONS: Asymptomatic STI was common and would not have been detected using a syndromic management approach. Although molecular screening for NG/CT is costly, in our study only four MSM needed to be screened to detect one case. This supports dual NG/CT molecular screening for MSM, which, in the case of confirmed NG infections, may trigger further culture-based investigations to determine gonococcal antimicrobial susceptibility in the current era of multi-drug resistant gonorrhoea.
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    Cryptococcal immune reconstitution inflammatory syndrome presenting with erosive bone lesions, arthritis and subcutaneous abscesses
    (2009) Burton, Rosie; Gogela, Neliswa; Rebe, Kevin; McNally, Matt; Meintjes, Graeme
    A 35-year-old South African man was diagnosed with pulmonary tuberculosis (TB) in August 2007 and started on a 6-month course of treatment (intensive phase of rifampicin, isoniazid, ethambutol and pyrazinamide for 2 months, followed by continuation phase of rifampicin and isoniazid for 4 months). His TB symptoms responded rapidly. At the time of TB diagnosis, he tested HIV positive. His CD4 cell count was 12 cells/µl with a viral load of more than 500 000 copies/ml. He commenced antiretroviral therapy (ART) 6 weeks later (stavudine, lamivudine and efavirenz). After 16 weeks on ART, his CD4 cell count was 62 cells/µl with an HIV viral load of less than 50 copies/ml. Five months after starting ART and having recently completed his TB treatment, he presented to his local clinic with pain and swelling of the left hypothenar eminence. He was referred to the specialist Hand Clinic, and incision and drainage was performed. Ten days later, this was repeated due to recurrence of symptoms. He experienced no further problems, and remained compliant on ART. Six months later, he presented to our hospital for the first time with tender red subcutaneous abscesses over his sternal notch (Fig. 1a) and in his left flank. His left elbow was swollen, red and extremely painful, with a severely restricted range of movement. A radiograph of the left elbow showed a lytic lesion in the posterior periarticular aspect of the humerus and erosion of the proximal end of the radius with loss of joint space (Fig. 1b). A chest radiograph showed a pulmonary infiltrate in the base of the left lung and erosive lesions in the left 5th and 6th ribs on the lateral film (Fig. 1c). Six weeks prior to this presentation, his CD4 cell count had been 81 cells/µl, and viral load less than 50 copies/ml.
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    Detectable HIV-1 in semen in individuals with very low blood viral loads
    (2020-03-05) Kariuki, Samuel M; Selhorst, Philippe; Norman, Jennifer; Cohen, Karen; Rebe, Kevin; Williamson, Carolyn; Dorfman, Jeffrey R
    Abstract Background Several reports indicate that a portion (5–10%) of men living with HIV-1 intermittently shed HIV-1 RNA into seminal plasma while on long term effective antiretroviral therapy (ART). This is highly suggestive of an HIV-1 reservoir in the male genital tract. However, the status of this reservoir in men living with HIV-1 who are not under treatment is underexplored and has implications for understanding the origins and evolution of the reservoir. Finding Forty-three HIV-1 positive, antiretroviral therapy naïve study participants attending a men’s health clinic were studied. Semen viral loads and blood viral loads were generally correlated, with semen viral loads generally detected in individuals with blood viral loads > 10,000 cp/ml. However, we found 1 individual with undetectable viral loads (<20cp/ml) and 2 individuals with very low blood viral load (97 and 333cp/ml), but with detectable HIV-1 in semen (485–1157 copies/semen sample). Blood viral loads in the first individual were undetectable when tested three times over the prior 5 years. Conclusions Semen HIV-1 viral loads are usually related to blood viral loads, as we confirm. Nonetheless, this was not true in a substantial minority of individuals suggesting unexpectedly high levels of replication in the male genital tract in a few individuals, despite otherwise effective immune control. This may reflect establishment of a local reservoir of HIV-1 populations.
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    Early severe morbidity and resource utilization in South African adults on antiretroviral therapy
    (BioMed Central Ltd, 2009) de Cherif, Teresa; Schoeman, Jan; Cleary, Susan; Meintjes, Graeme; Rebe, Kevin; Maartens, Gary
    BACKGROUND:High rates of mortality and morbidity have been described in sub-Saharan African patients within the first few months of starting highly active antiretroviral therapy (HAART). There is limited data on the causes of early morbidity on HAART and the associated resource utilization. METHODS: A cross-sectional study was conducted of medical admissions at a secondary-level hospital in Cape Town, South Africa. Patients on HAART were identified from a register and HIV-infected patients not on HAART were matched by gender, month of admission, and age group to correspond with the first admission of each case. Primary reasons for admission were determined by chart review. Direct health care costs were determined from the provider's perspective. RESULTS: There were 53 in the HAART group with 70 admissions and 53 in the no-HAART group with 60 admissions. The median duration of HAART was 1 month (interquartile range 1-3 months). Median baseline CD4 count in the HAART group was 57 x 106 cells/L (IQR 15-115). The primary reasons for admission in the HAART group were more likely to be due to adverse drug reactions and less likely to be due to AIDS events than the no-HAART group (34% versus 7%; p < 0.001 and 39% versus 63%; p = 0.005 respectively). Immune reconstitution inflammatory syndrome was the primary reason for admission in 10% of the HAART group. Lengths of hospital stay per admission and inpatient survival were not significantly different between the two groups. Five of the 15 deaths in the HAART group were due to IRIS or adverse drug reactions. Median costs per admission of diagnostic and therapeutic services (laboratory investigations, radiology, intravenous fluids and blood, and non-ART medications) were higher in the HAART group compared with the no-HAART group (US$190 versus US$111; p = 0.001), but the more expensive non-curative costs (overhead, capital, and clinical staff) were not significantly different (US$1199 versus US$1128; p = 0.525). CONCLUSIONS: Causes of early morbidity are different and more complex in HIV-infected patients on HAART. This results in greater resource utilization of diagnostic and therapeutic services.
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    Mortality in patients treated for tuberculous pericarditis in sub-Saharan Africa.
    (Health & Medical Publishing Group, 2008) Mayosi, Bongani M; Wiysonge, Charles Shey; Ntsekhe, Mpiko; Gumedze, Freedom; Volmink Jimmy A; Maartens, Gary; Aje, Akinyemi; Thomas, Baby M; Thomas, Kandathil M; Awotedu, Abolade A; Bongani, Thembela; Mntla, Phindile; Maritz, Frans; Blackett, Kathleen Ngu; Nkouonlack, Duquesne C; Burch, Vanessa C; Rebe, Kevin; Parrish, Andy; Sliwa, Karen; Vezi, Brian Z; Alam, Nowshad; Brown, Basil G; Gould, Trevor; Visser, Tim; Magula, Nombulelo P; Commerford, Patrick J
    Tuberculous pericarditis is one of the most severe forms of extrapulmonary tuberculosis, causing death or disability in a substantial proportion of affected people.1,2 In Africa, the incidence of tuberculous pericarditis is rising as a result of the HIV epidemic.3 The effect of HIV infection on survival in patients with tuberculous pericarditis is unknown.2,4 Whereas some investigators have suggested that HIV-infected patients with tuberculous pericarditis have a similar outcome to non-infected cases,5 others have shown that there may be an increase in mortality in HIV associated with tuberculous pericarditis.2,6,7 We established a prospective observational study, the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry, to obtain current information on the diagnosis, management and outcome of patients with presumed tuberculous pericarditis living in sub-Saharan Africa, where the burden of HIV infection is the greatest in the world.4,8-10 In this paper, we report the mortality rate and its predictors during the 6 months of antituberculosis treatment among patients enrolled in the regist
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    Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome
    (Lippincott, Williams & Wilkins, 2010) Meintjes, Graeme; Wilkinson, Robert J; Morroni, Chelsea; Pepper, Dominique J; Rebe, Kevin; Rangaka, Molebogeng X; Oni, Tolu; Maartens, Gary
    Objective: Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of antiretroviral therapy in resource-limited countries. We aimed to assess whether a 4 week course of prednisone would reduce morbidity in patients with paradoxical TB-IRIS without excess adverse events. Design: A randomised double blind placebo-controlled trial of prednisone (1.5mg/kg/day for 2 weeks then 0.75mg/kg/day for 2 weeks). Patients with immediately life-threatening TB-IRIS manifestations were excluded. Methods: The primary combined endpoint was days of hospitalization and outpatient therapeutic procedures, which were counted as one hospital day. Results: 110 participants were enrolled (55 to each arm). The primary combined endpoint was more frequent in the placebo than the prednisone arm (median hospital days 3 (IQR 0-9) and 0 (IQR 0-3) respectively; p=0.04). There were significantly greater improvements in symptoms, Karnofsky score, and quality of life (MOS-HIV) in the prednisone versus the placebo arm at 2 and 4 weeks, but not at later timepoints. Chest radiographs improved significantly more in the prednisone arm at weeks 2 (p=0.002) and 4 (p=0.02). Infections on study medication occurred in more participants in prednisone than placebo arm (27 vs 17 respectively; p=0.05), but there was no difference in severe infections (2 vs 4 respectively; p=0.40). Isolates from 10 participants were found to be resistant to rifampicin after enrollment. Conclusions: Prednisone reduced the need for hospitalisation and therapeutic procedures, and hastened improvements in symptoms, performance and quality of life. It is important to investigate for drug-resistant tuberculosis and other causes for deterioration before administering glucocorticoids.
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    Reduced referral and case fatality rates for severe symptomatic hyperlactataemia in a South African public sector antiretroviral programme: a retrospective observational study
    (BioMed Central Ltd, 2010) Schutz, Charlotte; Boulle, Andrew; Stead, Dave; Rebe, Kevin; Osler, Meg; Meintjes, Graeme
    BACKGROUND: Interventions to promote prevention and earlier diagnosis of severe symptomatic hyperlactataemia (SHL) were implemented in the Western Cape provincial antiretroviral programme (South Africa) from 2004. Interventions included clinician education, point-of-care lactate meters, switch from stavudine to zidovudine in high risk patients and stavudine dose reduction. This study assessed trends in referral rate, severity at presentation and case fatality rate for severe SHL. METHODS: Retrospective study of severe SHL cases diagnosed at a referral facility from 1 January 2003 to 31 December 2008. Severe SHL was defined as patients with compatible symptoms and serum lactate [greater than or equal to] 5 mmol/l attributable to antiretroviral therapy (ART). Cumulative ART exposure at referring ART clinics was used to calculate referral rates. RESULTS: There were 254 severe SHL cases. The referral rate (per thousand patient years [py] ART exposure) peaked in 2005 (20.4/1000py), but fell to 1.3/1000py by 2008 (incidence rate ratio [IRR] = 0.07, 95%CI 0.04-0.11). In 2003, 66.7% of cases presented with a standard bicarbonate (SHCO3) level <15 mmol/l, but this fell to 12.5% by 2008 (p for trend < 0.001). Case fatality rate fell from a peak of 33.3% in 2004 to 0% in 2008 (p for trend = 0.002). CONCLUSIONS: These trends suggest the interventions were associated with reduced referral, less severe metabolic acidosis at presentation and improved survival.
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    Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures
    (2009) Bicanic, Tihana; Brouwer, Annemarie E; Meintjes, Graeme; Rebe, Kevin; Limmathurotsakul, Direk; Chierakul, Wirongrong; Teparrakkul, Praprit; Loyse, Angela; White, Nicholas J; Wood, Robin; Jaffar, Shabbar; Harrison, Thomas
    Objectives: To assess impact of serial lumbar punctures on association between cerebrospinal fluid (CSF) opening pressure and prognosis in HIV-associated cryptococcal meningitis; to explore time course and relationship of opening pressure with neurological findings, CSF fungal burden, immune response, and CD4 cell count. Design: Evaluation of 163 HIV-positive ART-naive patients enrolled in three trials of amphotericin B-based therapy for cryptococcal meningitis in Thailand and South Africa. Methods: Study protocols required four lumbar punctures with measurements of opening pressure over the first 2 weeks of treatment and additional lumbar punctures if opening pressure raised. Fungal burden and clearance, CSF immune parameters, CD4 cell count, neurological symptoms and signs, and outcome at 2 and 10 weeks were compared between groups categorized by opening pressure at cryptococcal meningitis diagnosis. Results: Patients with higher baseline fungal burden had higher baseline opening pressure. High fungal burden appeared necessary but not sufficient for development of high pressure. Baseline opening pressure was not associated with CD4 cell count, CSF pro-inflammatory cytokines, or altered mental status. Day 14 opening pressure was associated with day 14 fungal burden. Overall mortality was 12% (20/162) at 2 weeks and 26% (42/160) at 10 weeks, with no significant differences between opening pressure groups. Conclusion: Studies are needed to define factors, in addition to fungal burden, associated with raised opening pressure. Aggressive management of raised opening pressure through repeated CSF drainage appeared to prevent any adverse impact of raised opening pressure on outcome in patients with cryptococcal meningitis. The results support increasing access to manometers in resource-poor settings and routine management of opening pressure in patients with cryptococcal meningitis.
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    Symptomatic relapse of HIV-associated cryptococcal meningitis in South Africa: The role of inadequate secondary prophylaxis
    (2010) Jarvis, Joseph N; Meintjes, Graeme; Williams, Zomzi; Rebe, Kevin; Harrison, Thomas S
    Objectives. Cryptococcal meningitis is the most common cause of adult meningitis in southern Africa. Much of this disease burden is thought to be due to symptomatic relapse of previously treated infection. We studied the contribution of inadequate secondary fluconazole prophylaxis to symptomatic relapses of cryptococcal meningitis. Design. A prospective observational study of patients presenting with laboratory-confirmed symptomatic relapse of HIV-associated cryptococcal meningitis between January 2007 and December 2008 at GF Jooste Hospital, a public sector adult referral hospital in Cape Town. Outcome measures. Relapse episodes were categorised into: (i) patients not taking fluconazole prophylaxis; (ii) immune reconstitution inflammatory syndrome (IRIS); and (iii) relapses occurring prior to ART in patients taking fluconazole. In-hospital mortality was recorded. Results. There were 69 relapse episodes, accounting for 23% of all cases of cryptococcal meningitis; 43% (N=30) of relapse episodes were in patients not receiving fluconazole prophylaxis, 45% (N=31) were due to IRIS, and 12% (N=8) were in patients pre-ART taking fluconazole. Patients developing relapse due to inadequate secondary prophylaxis had severe disease and high in-hospital mortality (33%). Of the 30 patients not taking fluconazole, 47% (N=14) had not been prescribed secondary prophylaxis by their health care providers. We documented no relapses due to fluconazole resistance in these patients who received amphotericin B as initial therapy. Conclusions. A large number of relapses of cryptococcal meningitis are due to failed prescription, dispensing and referral for or adherence to secondary fluconazole prophylaxis. Interventions to improve the use of secondary fluconazole prophylaxis are essential.