The role of glucocorticoids in the treatment of bacterial or fungal meningitis is controversial. In this trial, adjunctive dexamethasone therapy in patients with HIV-associated cryptococcal ...meningitis did not confer a benefit and was associated with increased adverse events.
Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection is estimated to cause more than 600,000 deaths each year, the vast majority in sub-Saharan Africa and in South and Southeast Asia.
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Among patients receiving combination antifungal therapy with amphotericin B and either flucytosine or fluconazole, mortality remains more than 30% at 10 weeks, and survivors often have substantial disability.
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There is a pressing need to improve outcomes. However, no new anticryptococcal agents are currently close to approval for clinical use, so innovative strategies are needed.
Adjunctive treatments, such as glucocorticoids, have shown some benefit in central nervous system (CNS) . . .
OBJECTIVE:To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women (‘Option B+’) in Malawi.
DESIGN, ...SETTING, AND PARTICIPANTS:We examined retention in care, from the date of ART initiation up to 6 months, for women in the Option B+ program. We analysed nationwide facility-level data on women who started ART at 540 facilities (n = 21 939), as well as individual-level data on patients who started ART at 19 large facilities (n = 11 534).
RESULTS:Of the women who started ART under Option B+ (n = 21 939), 17% appeared to be lost to follow-up 6 months after ART initiation. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count 350 cells/μl or less, to never return after their initial clinic visit odds ratio (OR) 5.0, 95% confidence interval (CI) 4.2–6.1. Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (OR 2.2, 95% CI 1.8–2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0 to 58%.
CONCLUSION:Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community or family-based models of care could improve its effectiveness.
In antiretroviral therapy (ART) scale-up programmes in sub-Saharan Africa viral load monitoring is not recommended. We wanted to study the impact of only using clinical and immunological monitoring ...on the diagnosis of virological ART failure under routine circumstances. Clinicians in two urban ART clinics in Malawi used clinical and immunological monitoring to identify adult patients for switching to second-line ART. If patients met clinical and/or immunological failure criteria of WHO guidelines and had a viral load <400 copies/ml there was misclassification of virological ART failure. Between January 2006 and July 2007, we identified 155 patients with WHO criteria for immunological and/or clinical failure. Virological ART failure had been misclassified in 66 (43%) patients. Misclassification was significantly higher in patients meeting clinical failure criteria (57%) than in those with immunological criteria (30%). On multivariate analysis, misclassification was associated with being on ART <2 years OR = 7.42 (2.63, 20.95) and CD4 > 200 cells/μl OR = 5.03 (2.05, 12.34). Active tuberculosis and Kaposi's sarcoma were the most common conditions causing misclassification of virological ART failure. Misclassification of virological ART failure occurs frequently using WHO clinical and immunological criteria of ART failure for poor settings. A viral load test confirming virological ART failure is therefore advised to avoid unnecessary switching to second-line regimens.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hypertension and diabetes prevalence is high in Africans. Data from HIV infected populations are limited, especially from Malawi. Integrating care for chronic non-communicable co-morbidities in ...well-established HIV services may provide benefit for patients by preventing multiple hospital visits but will increase the burden of care for busy HIV clinics.
Cross-sectional study of adults (≥18 years) at an urban and a rural HIV clinic in Zomba district, Malawi, during 2014. Hypertension and diabetes were diagnosed according to stringent criteria. Proteinuria, non-fasting lipids and cardio/cerebro-vascular disease (CVD) risk scores (Framingham and World Health Organization/International Society for Hypertension) were determined. The association of patient characteristics with diagnoses of hypertension and diabetes was studied using multivariable analyses. We explored the additional burden of care for integrated drug treatment of hypertension and diabetes in HIV clinics. We defined that burden as patients with diabetes and/or stage II and III hypertension, but not with stage I hypertension unless they had proteinuria, previous stroke or high Framingham CVD risk.
Nine hundred fifty-two patients were enrolled, 71.7% female, median age 43.0 years, 95.9% on antiretroviral therapy (ART), median duration 47.7 months. Rural and urban patients' characteristics differed substantially. Hypertension prevalence was 23.7% (95%-confidence interval 21.1-26.6; rural 21.0% vs. urban 26.5%; p = 0.047), of whom 59.9% had stage I (mild) hypertension. Diabetes prevalence was 4.1% (95%-confidence interval 3.0-5.6) without significant difference between rural and urban settings. Prevalence of proteinuria, elevated total/high-density lipoprotein-cholesterol ratio and high CVD risk score was low. Hypertension diagnosis was associated with increasing age, higher body mass index, presence of proteinuria, being on regimen zidovudine/lamivudine/nevirapine and inversely with World Health Organization clinical stage at ART initiation. Diabetes diagnosis was associated with higher age and being on non-standard first-line or second-line ART regimens.
Among patients in HIV care 26.6% had hypertension and/or diabetes. Close to two-thirds of hypertension diagnoses was stage I and of those few had an indication for antihypertensive pharmacotherapy. According to our criteria, 13.0% of HIV patients in care required drug treatment for hypertension and/or diabetes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) among patients on combination antiretroviral therapy (cART) in sub-Saharan Africa. We estimated the ...prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART.
HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS) was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery.
One hundred and six HIV positive patients, with median (range) age 39 (18-71) years, 73% female and median (range) CD4 count 323.5 (68-1039) cells/µl were studied. Symptomatic neurocognitive impairment was present in 15% (12% mild neurocognitive disorder MND, 3% HIV associated dementia HAD). A further 55% fulfilled Frascati criteria for asymptomatic neurocognitive impairment (ANI); however factors other than neurocognitive impairment could have confounded this estimate. Neither the symptomatic (MND and HAD) nor asymptomatic (ANI) forms of HAND were associated with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44 (CI. 0.234, 8.798; p = 0.696) and aOR 0.577 (CI. 0.09, 3.605; p = 0.556) respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a GDS of less than 0.6, consistent with normal neurocognition.
Fifteen percent of adult Malawians on cART had a diagnosis of MND or HAD. Subtherapeutic drug concentrations were found exclusively in patients with normal neurocognitive function suggesting HAND did not affect cART adherence. Further study of HAND requires more robust locally derived normative neurocognitive values and determination of the clinical relevance of ANI.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While dyslipidemia importantly contributes to increased cardiovascular disease risk among patients on antiretroviral therapy (ART), data on lipid patterns among African adults on ART are limited. We ...describe the prevalence of lipid abnormalities and associated factors in two HIV clinics in Malawi.
We conducted a cross-sectional study in 2014 and enrolled adult patients at a rural and an urban HIV clinic in Zomba district, Malawi. We recorded patient characteristics, CVD risk factors and anthropometric measurements, using the WHO STEPS validated instrument. Non-fasting samples were taken for determination of total cholesterol (TC), triglyceride (TG) and HDL-cholesterol (HDL-c) levels. Logistic regression analysis was used to determine factors associated with elevated TC and elevated TC/HDL-c ratio.
554 patients were enrolled, 50% at the rural HIV clinic, 72.7% were female, the median (IQR) age was 42 years (36-50); 97.3% were on ART, 84.4% on tenofovir/lamivudine/efavirenz, 17.5% were overweight/obese and 27.8%% had elevated waist/hip ratio. 15.5% had elevated TC, 15.9% reduced HDL-c, 28.7% had elevated TG and 3.8% had elevated TC/HDL-c ratio. Lipid abnormalities were similar in rural and urban patients. Women had significantly higher burden of elevated TC and TG whereas men had higher prevalence of reduced HDL-c. Waist-to-hip ratio was independently associated with elevated TC (aOR = 1.90; 95% CI: 1.17-3.10, p = 0.01) and elevated TC/HDL-c ratio (aOR = 3.50; 95% CI: 1.38-8.85, p = 0.008). Increasing age was independently associated with elevated TC level (aOR = 1.54, 95% CI 0.51-4.59 for age 31-45; aOR = 3.69, 95% CI 1.24-10.95 for age >45 years vs. ≤30 years; p-trend <0.01).
We found a moderate burden of dyslipidemia among Malawian adults on ART, which was similar in rural and urban patients but differed significantly between men and women. High waist-hip ratio predicted elevated TC and elevated TC/HDL-c ratio and may be a practical tool for CVD risk indication in resource limited settings.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The logistics of delivery will be improved, the risks of running out of stocks lessened, the need for multiple guidelines and training eliminated, and the likelihood of successful implementation ...increased. ... the proposed regimen is available in a fixed-dose combination of one tablet per day, can be safely used with antituberculosis drugs, is effective against hepatitis B virus, and can be used without routine laboratory monitoring of toxic effects.9 We propose to offer all HIV-infected pregnant women lifelong ART.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Evidence suggests that disclosure of HIV status between partners may influence prevention of maternal-to-child transmission of HIV (PMTCT) outcomes. We report partner disclosure in relation to ...maternal antiretroviral therapy (ART) uptake and adherence, and MTCT among postpartum HIV-infected Malawian women.
A cross-sectional mixed-method study was conducted as part of a nationally representative longitudinal cohort study. Between 2014-2016, all (34,637) mothers attending 54 under-5 clinics with their 4-26 week-old infants were approached, of which 98% (33,980) were screened for HIV; infants received HIV-1 DNA testing. HIV-exposure was confirmed in 3,566/33,980 (10.5%). Baseline data from mothers who were known to be HIV-infected at time of screening were included in the current analysis. Guardians (n = 17), newly diagnosed HIV-infected mothers (n = 256) and mothers or infants with undetermined HIV status (n = 30) were excluded. Data collected included socio-demographics, partner disclosure, maternal ART uptake, and adherence. Between 2016-2017, in-depth interviews and focus group discussions were conducted with adult mothers (n = 53) and their spouse/cohabiting partners (n = 19), adolescent mothers (n = 13), lost-to-follow up (LTFU) mothers (n = 22), community leaders (n = 23) and healthcare workers (n = 154).
Of 3153 known HIV-infected mothers, 2882 (91.4%) reported having a spouse/cohabiting partner. Among 2882 couples, both partners, one partner, and neither partner disclosed to each other in 2090 (72.5%), 622 (21.6%), and 169 (5.9%), respectively. In multivariable models, neither partner disclosing was associated with no maternal ART (aOR 4.7; 95%CI 2.5-8.8), suboptimal treatment adherence (aOR 1.8; 95%CI 1.1-2.8) and MTCT (aOR 2.1; 95%CI 1.1-4.1). Women's fear of blame by partners was central to decisions not to disclose within couples and when starting new relationships. LTFU mothers struggled to accept and disclose their status, hindering treatment initiation; some were unable to hide ART and feared involuntary disclosure.
Partner disclosure seems to play an important role in women's decisions regarding ART initiation and adherence. Inter-partner non-disclosure was associated with no ART uptake, suboptimal treatment adherence and MTCT.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long-term viral load (VL) suppression among HIV-positive, reproductive-aged women on ART is key to eliminating mother-to-child transmission (MTCT) but few data exist from sub-Saharan Africa. We ...report trends in post-partum VL in Malawian women on ART and factors associated with detectable VL up to 24 months post-partum.
1-6 months post-partum mothers, screened HIV-positive at outpatient clinics in Malawi, were enrolled (2014-2016) with their infants. At enrollment, 12- and 24-months post-partum socio-demographic and PMTCT indicators were collected. Venous samples were collected for determination of maternal VL (limit of detection 40 copies/ml). Results were returned to clinics for routine management.
596/1281 (46.5%) women were retained in the study to 24 months. Those retained were older (p<0.01), had higher parity (p = 0.03) and more likely to have undetectable VL at enrollment than those lost to follow-up (80.0% vs 70.2%, p<0.01). Of 590 women on ART (median 30.1 months; inter-quartile range 26.8-61.3), 442 (74.9%) with complete VL data at 3 visits were included in further analysis. Prevalence of detectable VL at 12 and 24 months was higher among women with detectable VL at enrollment than among those with undetectable VL (74 detectable VL results/66 women vs. 19/359; p<0.001). In multivariable analysis (adjusted for age, parity, education, partner disclosure, timing of ART start and self-reported adherence), detectable VL at 24 months was 9 times more likely among women with 1 prior detectable VL (aOR 9.0; 95%CI 3.5-23.0, p<0.001) and 226 times more likely for women with 2 prior detectable VLs (aOR 226.4; 95%CI 73.0-701.8, p<0.001).
Detectable virus early post-partum strongly increases risk of ongoing post-partum viremia. Due to high loss to follow-up, the true incidence of detectable VL over time is probably underestimated. These findings have implications for MTCT, as well as for the mothers, and call for intensified VL monitoring and targeted adherence support for women during pregnancy and post-partum.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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