Ilesh Jani

Accurate CD4 T-cell enumeration and antiretroviral drug toxicity monitoring in primary healthcare clinics using point-of-care testing.

Objective:To evaluate the accuracy of point-of-care tests (POCTs) for CD4 cell, clinical chemistry and hemoglobin in primary healthcare clinics in Mozambique. Design and methods:POCT and laboratory-based assays were conducted on adult HIV-positive patients enrolled consecutively at primary healthcare clinics in Mozambique. Patients were tested on-site with POCT CD4 (Pima), clinical chemistry (Reflotron) and hemoglobin (HemoCue) devices using finger prick blood. Results obtained on paired blood samples were used for agreement analysis (bias and limits of agreement). Repeatability analysis was also performed for POCT CD4 cell counting. Results:Primary health nurses operating the Pima, Reflotron and HemoCue POCT devices produced results with low levels of bias for CD4+ T-cell counts (−52.8 cells/μl), alanine aminotransferase (−0.2 U/l), aspartate aminotransferase (−4.0 U/l) and hemoglobin (0.95 g/dl). CD4+ T-cell counts in paired specimens of finger prick and venous blood tested on the POCT CD4 device were in close agreement (bias −9 cells/μl, coefficient of variation 10.6%). The repeatability of POCT CD4 cell counting was similar to that observed with laboratory instruments (bias −6.2 cells/μl, coefficient of variation 10.7% vs. bias −5.7 cells/μl, coefficient of variation 7.5%). Conclusion:Primary health clinic nurses generated accurate results for CD4+ T-cell counts, liver enzymes and hemoglobin using simple POC devices on finger prick samples at decentralized antiretroviral therapy (ART) clinics. POC diagnostics to monitor ART at primary healthcare level is technically feasible and should be utilized in efforts to decentralize HIV care and treatment.

How Point-of-Care Testing Could Drive Innovation in Global Health

In areas of limited resources, point-of-care diagnostic testing is being increasingly used to identify disease, determine prognosis, and monitor treatment. Investments in new diagnostics are starting to improve care. Health systems need to evolve to reap benefits for global health.

Sustainable HIV treatment in Africa through viral-load-informed differentiated care

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.This article has not been written or reviewed by Nature editors. Nature accepts no responsibility for the accuracy of the information provided.

Opportunities and Challenges for Cost-Efficient Implementation of New Point-of-Care Diagnostics for HIV and Tuberculosis

Stakeholders agree that supporting high-quality diagnostics is essential if we are to continue to make strides in the fight against human immunodeficiency virus (HIV) and tuberculosis. Despite the need to strengthen existing laboratory infrastructure, which includes expanding and developing new laboratories, there are clear diagnostic needs where conventional laboratory support is insufficient. Regarding HIV, rapid point-of-care (POC) testing for initial HIV diagnosis has been successful, but several needs remain. For tuberculosis, several new diagnostic tests have recently been endorsed by the World Health Organization, but a POC test remains elusive. Human immunodeficiency virus and tuberculosis are coendemic in many high prevalence locations, making parallel diagnosis of these conditions an important consideration. Despite its clear advantages, POC testing has important limitations, and laboratory-based testing will continue to be an important component of future diagnostic networks. Ideally, a strategic deployment plan should be used to define where and how POC technologies can be most efficiently and cost effectively integrated into diagnostic algorithms and existing test networks prior to widespread scale-up. In this fashion, the global community can best harness the tremendous capacity of novel diagnostics in fighting these 2 scourges.

Performance of the PointCare NOW System for CD4 Counting in HIV Patients Based on Five Independent Evaluations

Introduction Point-of-care (POC) CD4 testing can improve access to treatment by enabling decentralization and reducing patient loss-to-follow-up. As new POC CD4 technologies become available, their performance should be assessed before widespread deployment. This study reports the findings of five independent evaluations of the PointCare NOW CD4 system. Materials/Methods Evaluations were conducted in Southern Africa (Mozambique, South Africa) and North America (Canada, USA). 492 blood samples (55 from HIV-negative blood donors and 437 from HIV-infected patients, including 20 children aged between 12 and 59 months) were tested with both the PointCare NOW and reference flow cytometry instruments. Assessment of bias, precision and levels of clinical misclassification for absolute and percent CD4 count was conducted. Results PointCare NOW significantly overestimated CD4 absolute counts with a mean relative bias of +35.0%. Bias was greater in samples with CD4 counts below ≤350cells/µl (+51.3%) than in the CD4 >350cells/µl stratum (15.1%). Bias in CD4% had a similar trend with an overall relative mean bias of +25.6% and a larger bias for low CD4 stratum (+40.2%) than the higher CD4 stratum (+5.8%). Relative bias for CD4% in children was −6.8%. In terms of repeatability, PointCare NOW had a coefficient of variation of 11%. Using a threshold of 350cells/µl, only 47% of patients who qualified for antiretroviral therapy with reference CD4 testing, would have been eligible for treatment with PointCare NOW test results. This was 39% using a 200cells/µl threshold. Agreement with infant samples was higher, with 90% qualifying at a 25% eligibility threshold. Conclusion The performance of the PointCare NOW instrument for absolute and percent CD4 enumeration was inadequate for HIV clinical management in adults. In children, the small sample size was not large enough to draw a conclusion. This study also highlights the importance of independent evaluation of new diagnostic technology platforms before deployment.

Reducing mortality in HIV-infected infants and achieving the 90-90-90 target through innovative diagnosis approaches

Despite significant gains in access to early infant diagnosis (EID) over the past decade, most HIV‐exposed infants still do not get tested for HIV in the first two months of life. For those who are tested, the long turnaround time between when the sample is drawn and when the results are returned leads to a high rate of loss to follow‐up, which in turn means that few infected infants start antiretroviral treatment. Consequently, there continues to be high mortality from perinatally acquired HIV, and the ambitious goals of 90% of infected children identified, 90% of identified children treated and 90% of treated children with sustained virologic suppression by 2020 seem far beyond our reach. The objective of this commentary is to review recent advances in the field of HIV diagnosis in infants and describe how these advances may overcome long‐standing barriers to access to testing and treatment.

Cholera Epidemiology in Mozambique Using National Surveillance Data

BACKGROUND Mozambique has experienced cholera for several decades. This study was undertaken to evaluate epidemiologic patterns to assist in guiding public health interventions. METHODS We evaluated district-level Ministry of Health data for 123 consecutive weeks starting 1 January 2009. Cholera cases reported to the national level were based on clinical suspicion rather than microbiological confirmation. Time and space analyses with mapping and spatial statistics were undertaken. RESULTS During 2009-2011, Mozambique identified 220 deaths among the 25 431 reported suspected cholera cases (case fatality ratio [CFR], 0.87%). There were 108 outbreaks that occurred in 73 (50%) of Mozambiques 145 districts. Five distinct spatial clusters were identified involving inland and coastal as well as rural and urban populations. Among 78 outbreaks whose duration was known, average duration was 7.2 weeks (median, 6; range, 1-25). During weeks 1-3, 4-6, 7-9, and ≥ 10 after an outbreak, CFRs were 1.6%, 0.66%, 0.33%, and 0.25%, respectively. During 2010, districts that experienced an outbreak during 2009 had a CFR of 0.2% compared with 4.3% among other districts. DISCUSSION Mozambique continues to experience widespread cholera outbreaks of short duration involving distinct spatial clusters. These findings will influence choice of public health strategies.

Risk of extended viral resistance in human immunodeficiency virus-1-infected Mozambican children after first-line treatment failure.

Background: Resistant virus may be selected by sub-optimal control of HIV-1 replication during antiretroviral treatment. The incidence and profile of resistance in children receiving World Health Organization-recommended treatment remains to be evaluated on a large scale. Goals: Assessment of the frequency and profile of resistant virus in HIV-1-infected children, treated for at least 6 months with stavudine/zidovudine + lamivudine + nevirapine and presenting virological failure in a large access program in Maputo, Mozambique. Results: Cross-sectional evaluation of plasma HIV-1 viral load (VL) in 495 evaluable children among 512 treated for at least 6 months showed that 360 (72.7%) had a VL of <50 copies/mL of HIV-1 RNA. Genotypic resistance tests were performed in the 84 available samples from the 135 treated children with VL ≥50 copies/mL: 92% of the viruses were resistant to lamivudine and/or nevirapine, and 15% were resistant to stavudine. Twenty children (24%) harbored virus with a extended spectrum of cross-resistance defined as resistance to the 3 drugs of the combination received by the child and/or at least 1 resistance to a drug to which the child had never been exposed (abacavir: 5%, tenofovir: 6%, didanosine: 3.5% and the new generation non nucleoside inhibitor, etravirine: 6%). The only factor identified by multivariate analysis as being associated with this extended resistance profile was the duration of treatment (aOR: 6.67 [95% CI: 1.24–35.93], P = 0.015 for treatment >24 months) with a per month increase of 1.09 (1.02–1.16) P = 0.007. Conclusions: Residual viral replication in children receiving stavudine/zidovudine + lamivudine + nevirapine treatment is associated with a time-dependent risk of acquiring cross-resistance, including resistance to drugs currently used for second-line treatment and also to the new generation of non nucleoside reverse transcritpase inhibitors.

Surveillance of HIV drug resistance in children receiving antiretroviral therapy: a pilot study of the World Health Organization's generic protocol in Maputo, Mozambique.

Between 2007 and 2008, the Mozambique Ministry of Health conducted an assessment of human immunodeficiency virus drug resistance (HIVDR) using World Health Organization (WHO) methods in a cohort of children initiating antiretroviral therapy (ART) at the main pediatric ART referral center in Mozambique. It was shown that prior to ART initiation 5.4% of children had HIVDR that was associated with nevirapine perinatal exposure (P < .001). Twelve months after ART initiation, 77% had viral load suppression (<1000 copies/mL), exceeding the WHO target of ≥ 70%; 10.3% had HIVDR at 12 months. Baseline HIVDR (P = .04), maternal prevention of mother-to-child transmission (P = .02), and estimated days of missed medication (P = .03) predicted HIVDR at 12 months. As efforts to eliminate pediatric AIDS are intensified, implementation of ritonavir-boosted protease inhibitor regimens in children with prevention of mother-to-child transmission exposure may reduce risk of virological failure in our setting.

Treatment of Kaposi sarcoma in human immunodeficiency virus-1-infected Mozambican children with antiretroviral drugs and chemotherapy.

AIDS-associated Kaposi sarcoma occurs in children, but treatment experience reports are very scarce. A retrospective analysis of 28 children treated with highly active antiretroviral therapy and monthly paclitaxel showed unexpected results with 19 children in complete and sustainable remission, including those with the most severe form. Tolerance and feasibility were good, despite a lack of skilled staff in a low-resource setting.