David Maman

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.

Errors generated by a point-of-care CD4+ T-lymphocyte analyser: a retrospective observational study in nine countries

Abstract Objective To estimate the proportion of invalid results generated by a CD4+ T-lymphocyte analyser used by Médecins Sans Frontières (MSF) in field projects and identify factors associated with invalid results. Methods We collated 25 616 CD4+ T-lymphocyte test results from 39 sites in nine countries for the years 2011 to 2013. Information about the setting, user, training, sampling technique and device repair history were obtained by questionnaire. The analyser performs a series of checks to ensure that all steps of the analysis are completed successfully; if not, an invalid result is reported. We calculated the proportion of invalid results by device and by operator. Regression analyses were used to investigate factors associated with invalid results. Findings There were 3354 invalid test results (13.1%) across 39 sites, for 58 Alere PimaTM devices and 180 operators. The median proportion of errors per device and operator was 12.7% (interquartile range, IQR: 10.3–19.9) and 12.1% (IQR: 7.1–19.2), respectively. The proportion of invalid results varied widely by country, setting, user and device. Errors were not associated with settings, user experience or the number of users per device. Tests performed on capillary blood samples were significantly less likely to generate errors compared to venous whole blood. Conclusion The Alere Pima CD4+ analyser generated a high proportion of invalid test results, across different countries, settings and users. Most error codes could be attributed to the operator, but the exact causes proved difficult to identify. Invalid results need to be factored into the implementation and operational costs of routine CD4+ T-lymphocyte testing.

Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya.

HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15–59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7–17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8–11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2–14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2–6.2) for protease inhibitors. Three (3.4% 95% CI 0.8–10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.

Factors associated with HIV status awareness and Linkage to Care following home based testing in rural Malawi

HIV diagnosis and linkage to care are the main barriers in Africa to achieving the UNAIDS 90‐90‐90 targets. We assessed HIV‐positive status awareness and linkage to care among survey participants in Chiradzulu District, Malawi.

Field evaluation of GeneXpert® (Cepheid) HCV performance for RNA quantification in a Genotype 1 and 6 predominant patient population in Cambodia

GeneXpert® (Cepheid) is the only WHO prequalified platform for hepatitis C virus (HCV) nucleic acid amplification testing that is suitable for point‐of‐care use in resource‐limited contexts. However, its application is constrained by the lack of evidence on genotype 6 (GT6) HCV. We evaluated its field performance among a patient population in Cambodia predominantly infected with GT6. Between August and September 2017, we tested plasma samples obtained from consenting patients at Médecins Sans Frontières’ HCV clinic at Preah Kossamak Hospital for HCV viral load (VL) using GeneXpert® and compared its results to those obtained using COBAS® AmpliPrep/Cobas® TaqMan® HCV Quantitative Test, v2.0 (Roche) at the Institut Pasteur du Cambodge. Among 769 patients, 77% of the seropositive patients (n = 454/590) had detectable and quantifiable VL using Roche and 43% (n = 195/454) were GT6. The sensitivity and specificity of GeneXpert® against Roche were 100% (95% CI 99.2, 100.0) and 98.5% (95% CI 94.8, 99.8). The mean VL difference was −0.01 (95% CI −0.05, 0.02) log10 IU/mL for 454 samples quantifiable on Roche and −0.07 (95% CI −0.12, −0.02) log10 IU/mL for GT6 (n = 195). The limit of agreement (LOA) was −0.76 to 0.73 log10 IU/mL for all GTs and −0.76 to 0.62 log10 IU/mL for GT6. Twenty‐nine GeneXpert® results were outside the LOA. Frequency of error and the median turnaround time (TAT) for GeneXpert® were 1% and 0 days (4 days using Roche). We demonstrated that the GeneXpert® HCV assay has good sensitivity, specificity, quantitative agreement, and TAT in a real‐world, resource‐limited clinical setting among GT6 HCV patients.

High Proportions of Patients With Advanced HIV Are Antiretroviral Therapy Experienced: Hospitalization Outcomes From 2 Sub-Saharan African Sites

Abstract Background Human immunodeficiency virus (HIV) remains an important cause of hospitalization and death in low- and middle- income countries. Yet morbidity and in-hospital mortality patterns remain poorly characterized, with prior antiretroviral therapy (ART) exposure and treatment failure status largely unknown. Methods We studied HIV-infected inpatients aged ≥13 years from cohorts in Kenya and the Democratic Republic of Congo (DRC), assessing clinical and demographic characteristics and hospitalization outcomes. Kenyan inpatients were prospectively enrolled during hospitalization; identical retrospective data were extracted for Congolese patients meeting the study criteria using routine medical information. Results Among 338 HIV-infected patients in Kenya and 411 in DRC, 83.7% (95% confidence interval [CI], 79.4%–87.3%) and 97.3% (95% CI, 95.2%–98.5%), were admitted with advanced disease (defined as CD4 <200 cells/µL or World Health Organization stage 3/4 illness). Among inpatients with advanced HIV, 35.4% and 21.7% were ART-naive at admission. Patients under care had a median time of 44.1 (interquartile range [IQR], 18.4–90.5) months and 55.9 (IQR, 28.1–99.6) months on treatment; 17.2% (95% CI, 13.5%–21.6%) and 29.6% (95% CI, 25.4%–34.3%) died, 25.9% (95% CI, 16.0%–39.0%) and 22.5% (95% CI, 15.8%–31.0%) of these within 48 hours. Conclusions Across 2 diverse clinical contexts in sub-Saharan Africa, advanced HIV inpatients were frequently admitted with low CD4 counts, often failing first-line ART. Earlier identification of treatment failure and rapid switching to second-line ART are needed.

High rates of hypertension, diabetes, elevated low-density lipoprotein cholesterol, and cardiovascular disease risk factors in HIV-infected patients: results from a cross-sectional survey in Malawi

Objectives: Data on cardiovascular disease risks among HIV-infected patients taking antiretroviral therapy (ART) over long periods of time are lacking in Sub-Saharan Africa. Methods: A cross-sectional study was conducted in Chiradzulu, Malawi from December 2015 to June 2016. HIV-infected persons on ART for more than 10 years (patients) and HIV-negative individuals (controls) from selected clinics participated. Following informed consent, a standardized questionnaire, clinical and laboratory examinations were performed. The prevalence of cardiovascular disease risk factors was calculated and stratified by age group. Results: Overall, 379 HIV-infected patients and 356 controls participated. Median time on ART among patients was 11.6 years (interquartile range 10.6–12.4).Within the 30–44, 45–59, and at least 60-year age groups, respectively, the prevalence of hypertension was 10.8, 20.4, and 44.7% among patients and 6.1, 25.8, and 42.9% among controls. Hypertension was previously undiagnosed in 60.3% patients and 37.0% controls with elevated blood pressure. The prevalence of diabetes within the respective age groups was 5.0, 6.4, and 13.2% among patients, and 3.4, 4.2, and 1.7% among controls. HIV-infected patients were more likely to have an glycated hemoglobin at least 6.0% (adjusted odds ratio 1.9; 95% confidence interval 1.1–3.2, P = 0.02). Prevalence of low-density lipoprotein cholesterol more than 130 mg/dl within the respective age groups was 8.0, 15.4, and 23.7% among patients and 1.8, 12.5, and 11.8% among controls. Conclusion: Noncommunicable diseases were a significant burden in Malawi, with high prevalence of hypercholesterolemia in all survey participants and an especially acute diabetes burden among older HIV infected. Hypertension screening and treatment services are needed among identified high-risk groups to cover unmet needs.