Browsing by Author "Wandeler, Gilles"

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    Open Access
    Hepatitis B infection, viral load and resistance in HIV-infected patients in Mozambique and Zambia
    (Public Library of Science, 2016) Wandeler, Gilles; Musukuma, Kalo; Zürcher, Samuel; Vinikoor, Michael J; Llenas-García, Jara; Aly, Mussa M; Mulenga, Lloyd; Chi, Benjamin H; Ehmer, Jochen; Hobbins, Michael A; Bolton-Moore, Carolyn; Hoffmann, Christopher J; Egger, Matthias; IeDEA-Southern Africa
    BACKGROUND: Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. METHODS: We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine ® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. RESULTS: Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192-8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22-5.53) and CD4 cell count below 200/μl (2.58, 1.20-5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. CONCLUSION: One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults.
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    Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study
    (Public Library of Science, 2013) Estill, Janne; Egger, Matthias; Johnson, Leigh F; Gsponer, Thomas; Wandeler, Gilles; Davies, Mary-Ann; Boulle, Andrew; Wood, Robin; Garone, Daniela; Stringer, Jeffrey S A
    Objectives Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference. Design: Mathematical modelling study based on data from ART programmes. METHODS: We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained. RESULTS: RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74-1.03) in scenario A, 0.94 (0.77-1.02) with delayed switching (scenario B) and 0.80 (0.44-1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality. CONCLUSIONS: VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.
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    Retention in care of HIV-infected children from HIV test to start of antiretroviral therapy: systematic review
    (Public Library of Science, 2013) Mugglin, Catrina; Wandeler, Gilles; Estill, Janne; Egger, Matthias; Bender, Nicole; Davies, Mary-Ann; Keiser, Olivia
    BACKGROUND: In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART). The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined. METHODS: We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate. RESULTS: Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years. CONCLUSION: Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings.