Clair Mills

Multidrug-Resistant Tuberculosis Treatment Outcomes in Karakalpakstan, Uzbekistan: Treatment Complexity and XDR-TB among Treatment Failures

Background A pilot programme to treat multidrug-resistant TB (MDR-TB) was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. Methodology This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. Principal Findings Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38%) were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62%) patients, with 13 (15%) dying during treatment, 12 (14%) defaulting and 8 (8%) failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82%) patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB) was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. Conclusions While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment.

The Evaluation of a Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm

Background Concerns about false-positive HIV results led to a review of testing procedures used in a Médecins Sans Frontières (MSF) HIV programme in Bukavu, eastern Democratic Republic of Congo. In addition to the WHO HIV rapid diagnostic test algorithm (RDT) (two positive RDTs alone for HIV diagnosis) used in voluntary counselling and testing (VCT) sites we evaluated in situ a practical field-based confirmation test against western blot WB. In addition, we aimed to determine the false-positive rate of the WHO two-test algorithm compared with our adapted protocol including confirmation testing, and whether weakly reactive compared with strongly reactive rapid test results were more likely to be false positives. Methodology/Principal Findings 2864 clients presenting to MSF VCT centres in Bukavu during January to May 2006 were tested using Determine HIV-1/2® and UniGold HIV® rapid tests in parallel by nurse counsellors. Plasma samples on 229 clients confirmed as double RDT positive by laboratory retesting were further tested using both WB and the Orgenics Immunocomb Combfirm® HIV confirmation test (OIC-HIV). Of these, 24 samples were negative or indeterminate by WB representing a false-positive rate of the WHO two-test algorithm of 10.5% (95%CI 6.6-15.2). 17 of the 229 samples were weakly positive on rapid testing and all were negative or indeterminate by WB. The false-positive rate fell to 3.3% (95%CI 1.3–6.7) when only strong-positive rapid test results were considered. Agreement between OIC-HIV and WB was 99.1% (95%CI 96.9–99.9%) with no false OIC-HIV positives if stringent criteria for positive OIC-HIV diagnoses were used. Conclusions The WHO HIV two-test diagnostic algorithm produced an unacceptably high level of false-positive diagnoses in our setting, especially if results were weakly positive. The most probable causes of the false-positive results were serological cross-reactivity or non-specific immune reactivity. Our findings show that the OIC-HIV confirmation test is practical and effective in field contexts. We propose that all double-positive HIV RDT samples should undergo further testing to confirm HIV seropositivity until the accuracy of the RDT testing algorithm has been established at programme level.

Universal access: the benefits and challenges in bringing integrated HIV care to isolated and conflict affected populations in the Republic of Congo.

The Pool region of the Republic of Congo is an isolated, conflict-affected area with under-resourced and poorly functioning health care services. Despite significant AIDS-related mortality and morbidity in this area, and a national level commitment to universal HIV care, HIV has been largely neglected. In 2005 Médecins Sans Frontières decided to introduce HIV care activities. However, in this setting of high basic health care needs, limited medical resources and competing medical priorities, a vertical HIV programme was not suitable. This paper describes the process of integrating HIV care and treatment into basic health services, the clinical outcomes of 222 patients started on antiretroviral treatment (ART), and the benefits to communities and health care systems. Key lessons learned include the use of multi-skilled human resources, the step-wise implementation of HIV activities, the initial engagement of an HIV experienced staff member, the use of simplified and adapted testing, clinical and monitoring protocols and drug regimens, the introduction of more complex monitoring tools to simplify clinical management decisions and intensive staff education regarding the benefits of HIV integration. This project in a rural and remote conflict-affected setting demonstrates that integrated HIV programs can save lives and play a key role in helping to achieve universal access to ART in Africa.

Provision of antiretroviral treatment in conflict settings: the experience of Médecins Sans Frontières

IntroductionMany countries ravaged by conflict have substantial morbidity and mortality attributed to HIV/AIDS yet HIV treatment is uncommonly available. Universal access to HIV care cannot be achieved unless the needs of populations in conflict-affected areas are addressed.MethodsFrom 2003 Médecins Sans Frontières introduced HIV care, including antiretroviral therapy, into 24 programmes in conflict or post-conflict settings, mainly in sub-Saharan Africa. HIV care and treatment activities were usually integrated within other medical activities. Project data collected in the Fuchia software system were analysed and outcomes compared with ART-LINC data. Programme reports and other relevant documents and interviews with local and headquarters staff were used to develop lessons learned.ResultsIn the 22 programmes where ART was initiated, more than 10,500 people were diagnosed with HIV and received medical care, and 4555 commenced antiretroviral therapy, including 348 children. Complete data were available for adults in 20 programmes (n = 4145). At analysis, 2645 (64%) remained on ART, 422 (10%) had died, 466 (11%) lost to follow-up, 417 (10%) transferred to another programme, and 195 (5%) had an unclear outcome. Median 12-month mortality and loss to follow-up were 9% and 11% respectively, and median 6-month CD4 gain was 129 cells/mm 3.Patient outcomes on treatment were comparable to those in stable resource-limited settings, and individuals and communities obtained significant benefits from access to HIV treatment. Programme disruption through instability was uncommon with only one program experiencing interruption to services, and programs were adapted to allow for disruption and population movements. Integration of HIV activities strengthened other health activities contributing to health benefits for all victims of conflict and increasing the potential sustainability for implemented activities.ConclusionsWith commitment, simplified treatment and monitoring, and adaptations for potential instability, HIV treatment can be feasibly and effectively provided in conflict or post-conflict settings.

Outcomes of a Remote, Decentralized Health Center-Based HIV/AIDS Antiretroviral Program in Zambia, 2003 to 2007

A cross-sectional study of patients living with HIV/ AIDS treated during 2003 to 2007 in decentralized, rural health centers in Zambia was performed to measure virological outcomes after 12 months of antiretroviral therapy and identify factors associated with virological failure. Data from 228 patients who started antiretroviral therapy >12 months prior were analyzed. In all, 93% received stavudine + lamivudine + nevirapine regimens, and median antiretroviral therapy duration was 23.5 months (interquartile range 20-28). Of the 205 patients tested for viral load, 177 (86%) had viral load <1000 copies/mL. Probability of developing virological failure (viral load >1000 copies/mL) was 8.9% at 24 months and 19.6% at 32 months. Predictors for virological failure were <100% adherence, body mass index <18.5 kg/m2, and women <40 years old. Of those with virological failure who underwent 3 to 6 months of intensive adherence counseling, 45% obtained virological success. In a remote, resource-limited setting in decentralized health centers, virological and immunological assessments of patients on antiretroviral therapy >12 months showed that positive health outcomes are achievable.

Predictors of Raised Viral Load during Antiretroviral Therapy in Patients with and without Prior Antiretroviral Use: A Cross-Sectional Study

Objectives In Lagos, Nigeria, Médecins Sans Frontières (MSF) and the Ministry of Health (MoH) commenced free antiretroviral treatment (ART) in a hospital-based clinic. We performed a cross-sectional study to compare factors associated with raised viral load between patients with (“experienced”) and without (“naïve”) prior antiretroviral (ARV) exposure at commencement of ART at the clinic. We also examined factors influencing ARV adherence in experienced patients prior to clinic entry. Methods We included adult patients receiving ART from MSF who answered a questionnaire about previous antiretroviral use. Multivariate logistic regression was used to estimate odds ratios (OR) for raised viral load (≥1000 copies/mL). Results 1246 (96%) patients answered: 1075 (86%) reported no, and 171 (14%) some, prior ARV exposure. ARV-naïve patients were more immunosuppressed at baseline: 65% vs 37% (p<0.001) had CD4<200; 17% vs 9% (p = 0.013) were WHO stage 4. Proportionately more experienced than naïve patients had raised viral loads (20% vs 9%, p<0.001) on ART in the MSF/MoH clinic. Raised viral load was associated with prior ARV experience (adjusted OR = 3.74, 95%CI 2.09–6.70, p<0.001) and complete interruption of current ART (adjusted OR = 3.71, 95%CI 2.06–6.68, p<0.001). Higher CD4 at time of VL and a higher self-rated score of recent adherence were associated with lower OR of a raised viral load. Among experienced patients who missed pills before joining MSF/MoH, most common reasons were because ARVS were not affordable (58%) or available (33%), with raised viral load associated with being unsure how to take them (OR = 3.16, 95%CI 1.10–9.12, p = 0.033). Conclusions Patients previously exposed to ARVs had increased OR of raised viral load. The cost and availability of ARVs were common reasons for missing ARVs before joining the MSF/MoH clinic, and inadequate patient knowledge was associated with raised viral load.

Antibiotic resistance in Palestine: an emerging part of a larger crisis

Supporting previous letters published in The BMJ about the violent response of Israeli forces to Palestinian protestors in Gaza,123 Medecins Sans Frontieres (MSF) has received 2228 trauma patients from April to September. The total number of injured has now reached 20 833, with 191 deaths.4 About 90% of Palestinian patients seeking care from MSF have had lower limb injuries from gunshot wounds, …