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Trans R Soc Trop Med Hyg. 1 January 2006; Volume 100 (Issue 1); DOI:10.1016/j.trstmh.2005.06.018
Zachariah R, Teck R, Ascurra O, Humblet P, Harries AD
Trans R Soc Trop Med Hyg. 1 January 2006; Volume 100 (Issue 1); DOI:10.1016/j.trstmh.2005.06.018
Malawi offers antiretroviral treatment (ART) to all HIV-positive adults who are clinically classified as being in WHO clinical stage III or IV without 'universal' CD4 testing. This study was conducted among such adults attending a rural district hospital HIV/AIDS clinic (a) to determine the proportion who have CD4 counts >or=350 cells/microl, (b) to identify risk factors associated with such CD4 counts and (c) to assess the validity and predictive values of possible clinical markers for CD4 counts >or=350 cells/microl. A CD4 count >or=350 cells/microl was found in 36 (9%) of 401 individuals who are thus at risk of being placed prematurely on ART. A body mass index (BMI) >22 kg/m(2), the absence of an active WHO indicator disease at the time of presentation for ART, and a total lymphocyte count >1,200 cells/microl were significantly associated with such a CD4 count. The first two of these variables could serve as clinical markers for selecting subgroups of patients who should undergo CD4 testing. In a resource-limited district setting, assessing the BMI and checking for active opportunistic infections are routine clinical procedures that could be used to target CD4 measurements, thereby minimising unnecessary CD4 measurements, unnecessary (too early) treatment and costs.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 September 2004
Zachariah R, Teck R, Harries AD, Humblet P
Int J Tuberc Lung Dis. 1 September 2004
In a rural district in Malawi, poorly motivated health personnel, shortages of human and financial resources, weak dialogue between existing tuberculosis (TB) and human immunodeficiency virus (HIV) programmes and poor community involvement are constraints to establishing joint TB-HIV interventions. The presence of a non-governmental organisation (NGO), Médecins Sans Frontières (MSF), in the health care delivery system provided an opportunity to bridge some of these gaps. The main inputs provided by MSF included additional staff, supplementary drugs including antiretroviral drugs, technical assistance and infrastructure development. The introduction of a scheme of monthly performance-linked incentives for health personnel proved successful in improving their performance, as judged by attendance rates as well as the quality and quantity of activities. This initiative also provided the district management with a tool for exerting pressure on health staff to improve their performance. The availability of independent NGO funds and a logistics team for construction of new infrastructure allowed the rapid initiation of new interventions at the district level without having to wait for disbursements of funds from the central level. This introduced a new dynamic of decentralised operational flexibility at the district level which improved access to care and support for people with TB-HIV.
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Trans R Soc Trop Med Hyg. 1 January 2007; Volume 101 (Issue 1); DOI:10.1016/j.trstmh.2006.05.010
Zachariah R, Teck R, Buhendwa L, Fitzerland M, Labana S, et al.
Trans R Soc Trop Med Hyg. 1 January 2007; Volume 101 (Issue 1); DOI:10.1016/j.trstmh.2006.05.010
A study was carried in a rural district in Malawi among HIV-positive individuals placed on antiretroviral treatment (ART) in order to verify if community support influences ART outcomes. Standardized ART outcomes in areas of the district with and without community support were compared. Between April 2003 (when ART was started) and December 2004 a total of 1634 individuals had been placed on ART. Eight hundred and ninety-five (55%) individuals were offered community support, while 739 received no such support. For all patients placed on ART with and without community support, those who were alive and continuing ART were 96 and 76%, respectively (P<0.001); death was 3.5 and 15.5% (P<0.001); loss to follow-up was 0.1 and 5.2% (P<0.001); and stopped ART was 0.8 and 3.3% (P<0.001). The relative risks (with 95% CI) for alive and on ART [1.26 (1.21-1.32)], death [0.22 (0.15-0.33)], loss to follow-up [0.02 (0-0.12)] and stopped ART [0.23 (0.08-0.54)] were all significantly better in those offered community support (P<0.001). Community support is associated with a considerably lower death rate and better overall ART outcomes. The community might be an unrecognized and largely 'unexploited resource' that could play an important contributory role in countries desperately trying to scale up ART with limited resources.
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Clin Infect Dis. 1 May 2007; Volume 44 (Issue 9); DOI:10.1086/513433
O'Brien DP, Sauvageot D, Olson D, Schaeffer M, Humblet P, et al.
Clin Infect Dis. 1 May 2007; Volume 44 (Issue 9); DOI:10.1086/513433
A study of 568 children aged <5 years who commenced nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in resource-limited settings revealed good early outcomes. After 12 months of antiretroviral therapy, survival probability was 0.89 (95% confidence interval, 0.86-0.92), with no significant difference among children stratified on the basis of baseline immunological levels; 62% attained a CD4 cell percentage >25%, and 7% continued to have a CD4 cell percentage <15%.
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AIDS. 3 October 2006; Volume 20 (Issue 15); 1955-1960.; DOI:10.1097/01.aids.0000247117.66585.ce
O'Brien DP, Sauvageot D, Zachariah R, Humblet P
AIDS. 3 October 2006; Volume 20 (Issue 15); 1955-1960.; DOI:10.1097/01.aids.0000247117.66585.ce
OBJECTIVES
To (a) determine early treatment outcomes and (b) assess safety in children treated with adult fixed-dose combination (FDC) antiretroviral tablets.
SETTING
Sixteen Medecins Sans Frontieres (MSF) HIV programs in eight countries in resource-limited settings (RLS).
METHODS
Analysis of routine program data gathered June 2001 to March 2005.
RESULTS
A total of 1184 children [median age, 7 years; inter-quartile range (IQR), 4.6-9.3] were treated with antiretroviral therapy (ART) of whom 616(52%) were male. At ART initiation, Centres for Disease Control stages N, A, B and C were 9, 14, 38 and 39%, respectively. Children were followed up for a median period of 6 months (IQR, 2-12 months). At 12 months the median CD4 percentage gain in children aged 18-59 months was 15% (IQR, 6-18%), and the percentage with CD4 gain < 15% was reduced from 85% at baseline to 11%. In those aged 60-156 months, median CD4 cell count gain was 275 cells/microl (IQR, 84-518 cells/microl), and the percentage with CD4 < 200 cells/mul reduced from 51% at baseline to 11%. Treatment outcomes included; 1012 (85%) alive and on ART, 36 (3%) deaths, 15 (1%) stopped ART, 89 (8%) lost to follow-up, and 31 (3%) with unknown outcomes. Overall probability of survival at 12 months was 0.87 (0.84-0.89). Side effects caused a change to alternative antiretroviral drugs in 26 (2%) but no deaths.
CONCLUSIONS
Very satisfactory early outcomes can be achieved in children in RLS using generic adult FDC antiretroviral tablets. These findings strongly favour their use as an "interim solution" for scaling-up ART in children; however, more appropriate pediatric antiretroviral drugs remain urgently needed.
To (a) determine early treatment outcomes and (b) assess safety in children treated with adult fixed-dose combination (FDC) antiretroviral tablets.
SETTING
Sixteen Medecins Sans Frontieres (MSF) HIV programs in eight countries in resource-limited settings (RLS).
METHODS
Analysis of routine program data gathered June 2001 to March 2005.
RESULTS
A total of 1184 children [median age, 7 years; inter-quartile range (IQR), 4.6-9.3] were treated with antiretroviral therapy (ART) of whom 616(52%) were male. At ART initiation, Centres for Disease Control stages N, A, B and C were 9, 14, 38 and 39%, respectively. Children were followed up for a median period of 6 months (IQR, 2-12 months). At 12 months the median CD4 percentage gain in children aged 18-59 months was 15% (IQR, 6-18%), and the percentage with CD4 gain < 15% was reduced from 85% at baseline to 11%. In those aged 60-156 months, median CD4 cell count gain was 275 cells/microl (IQR, 84-518 cells/microl), and the percentage with CD4 < 200 cells/mul reduced from 51% at baseline to 11%. Treatment outcomes included; 1012 (85%) alive and on ART, 36 (3%) deaths, 15 (1%) stopped ART, 89 (8%) lost to follow-up, and 31 (3%) with unknown outcomes. Overall probability of survival at 12 months was 0.87 (0.84-0.89). Side effects caused a change to alternative antiretroviral drugs in 26 (2%) but no deaths.
CONCLUSIONS
Very satisfactory early outcomes can be achieved in children in RLS using generic adult FDC antiretroviral tablets. These findings strongly favour their use as an "interim solution" for scaling-up ART in children; however, more appropriate pediatric antiretroviral drugs remain urgently needed.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 March 2005
Teck R, Ascurra O, Gomani P, Manzi M, Pasulani O, et al.
Int J Tuberc Lung Dis. 1 March 2005
SETTING: Thyolo district, Malawi. OBJECTIVES: To determine in HIV-positive individuals aged over 13 years CD4 lymphocyte counts in patients classified as WHO Clinical Stage III and IV and patients with active and previous tuberculosis (TB). DESIGN: Cross-sectional study. METHODS: CD4 lymphocyte counts were determined in all consecutive HIV-positive individuals presenting to the antiretroviral clinic in WHO Stage III and IV. RESULTS: A CD4 lymphocyte count of < or = 350 cells/microl was found in 413 (90%) of 457 individuals in WHO Stage III and IV, 96% of 77 individuals with active TB, 92% of 65 individuals with a history of pulmonary TB (PTB) in the last year, 91% of 89 individuals with a previous history of PTB beyond 1 year, 81% of 32 individuals with a previous history of extra-pulmonary TB, 93% of 107 individuals with active or past TB with another HIV-related disease and 89% of 158 individuals with active or past TB without another HIV-related disease. CONCLUSIONS: In our setting, nine of 10 HIV-positive individuals presenting in WHO Stage III and IV and with active or previous TB have CD4 counts of < or = 350 cells/microl. It would thus be reasonable, in this or similar settings where CD4 counts are unavailable for clinical management, for all such patients to be considered eligible for antiretroviral therapy.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 March 2005
Zachariah R, Teck R, Ascurra O, Gomani P, Manzi M, et al.
Int J Tuberc Lung Dis. 1 March 2005
The World Health Organization (WHO) has set a target of treating 3 million people with antiretroviral treatment (ART) by 2005. In sub-Saharan Africa, HIV-positive tuberculosis (TB) patients could significantly contribute to this target. ART (stavudine/lamivudine/nevirapine) was initiated in Thyolo district, Malawi, in April 2003, and all HIV-positive TB patients were considered eligible and offered ART. Despite this, only 44 (13%) of 352 TB patients were eventually started on ART by the end of November 2003. Most TB patients leave hospital after 2 weeks to complete the initial phase of anti-tuberculosis treatment (rifampicin-based) in the community, and ART is offered to HIV-positive TB patients after they have started the continuation phase of treatment (isoniazid/ ethambutol). ART is only offered at hospital, while the majority of TB patients take their continuation phase of anti-tuberculosis treatment from health centres. HIV-positive TB patients therefore find it difficult to access ART. In this paper, we discuss a series of options to increase the uptake of ART among HIV-positive TB patients. The main options are: 1) to hospitalise HIV-positive TB patients with a view to starting ART in the continuation phase in hospital; 2) to decentralise ART delivery so ART can be delivered at health centres; 3) to replace nevirapine with efavirenz so ART can be started earlier in the initial phase of anti-tuberculosis treatment. Decentralisation of ART from hospitals to health centres would greatly improve ART access.
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Trop Med Int Health. 1 December 2005; Volume 10 (Issue 12); DOI:10.1111/j.1365-3156.2005.01526.x
Manzi M, Zachariah R, Teck R, Buhendwa L, Kazima J, et al.
Trop Med Int Health. 1 December 2005; Volume 10 (Issue 12); DOI:10.1111/j.1365-3156.2005.01526.x
SETTING: Thyolo District Hospital, rural Malawi. OBJECTIVES: In a prevention of mother-to-child HIV transmission (PMTCT) programme, to determine: the acceptability of offering 'opt-out' voluntary counselling and HIV-testing (VCT); the progressive loss to follow up of HIV-positive mothers during the antenatal period, at delivery and to the 6-month postnatal visit; and the proportion of missed deliveries in the district. DESIGN: Cohort study. METHODS: Review of routine antenatal, VCT and PMTCT registers. RESULTS: Of 3136 new antenatal mothers, 2996 [96%, 95% confidence interval (CI): 95-97] were pre-test counselled, 2965 (95%, CI: 94-96) underwent HIV-testing, all of whom were post-test counselled. Thirty-one (1%) mothers refused HIV-testing. A total of 646 (22%) individuals were HIV-positive, and were included in the PMTCT programme. Two hundred and eighty-eight (45%) mothers and 222 (34%) babies received nevirapine. The cumulative loss to follow up (n=646) was 358 (55%, CI: 51-59) by the 36-week antenatal visit, 440 (68%, CI: 64-71) by delivery, 450 (70%, CI: 66-73) by the first postnatal visit and 524 (81%, CI: 78-84) by the 6-month postnatal visit. This left just 122 (19%, CI: 16-22) of the initial cohort still in the programme. The great majority (87%) of deliveries occurred at peripheral sites where PMTCT was not available. CONCLUSIONS: In a rural district hospital setting, at least 9 out of every 10 mothers attending antenatal services accepted VCT, of whom approximately one-quarter were HIV-positive and included in the PMTCT programme. The progressive loss to follow up of more than three-quarters of this cohort by the 6-month postnatal visit demands a 'different way of acting' if PMTCT is to be scaled up in our setting.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 November 2003
Zachariah R, Spielmann M P, Harries AD, Gomani P, Graham SM, et al.
Int J Tuberc Lung Dis. 1 November 2003
SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with active case finding among household contacts of smear-positive pulmonary tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of child contacts aged under 6 years who are placed on isoniazid (INH) preventive therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding was conducted among household contacts, and the uptake of INH preventive therapy in children was assessed. RESULTS: There were 189 index TB cases and 985 household contacts. Human immunodeficiency virus (HIV) prevalence among index cases was 69%. Prevalence of TB by passive case finding among 524 household contacts was 0.19% (191/100000), which was significantly lower than with active finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113 children received the drug. Transport costs associated with chest X-ray (CXR) screening were the major reason for low INH uptake. CONCLUSIONS: Where the majority of TB patients are HIV-positive, active case finding among household contacts yields nine times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH prophylaxis.
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AIDS. 11 July 2008; Volume 22 (Issue 11); DOI:10.1097/QAD.0b013e3282fa75b9
Pujades-Rodríguez M, O'Brien DP, Humblet P, Calmy A
AIDS. 11 July 2008; Volume 22 (Issue 11); DOI:10.1097/QAD.0b013e3282fa75b9
OBJECTIVES: To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival. DESIGN/METHODS: We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan-Meier methods, and mortality predictors were investigated using Poisson regression. RESULTS: Of 48,338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/microl (interquartile ratio 39-200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/microl. CONCLUSION: The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment.