RESUMEN
BACKGROUND: Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While the use of plasma specimens is the standard for viral load testing, its use is restricted by the limited ambient temperature stability of viral load biomarkers in whole blood and plasma during storage and transportation and the limited cold chain available between many health care facilities in resource-limited settings. Alternative specimen types and technologies, such as dried blood spots, may address these issues and increase access to viral load testing; however, their technical performance is unclear. To address this, we conducted a meta-analysis comparing viral load results from paired dried blood spot and plasma specimens analyzed with commonly used viral load testing technologies. METHODS AND FINDINGS: Standard databases, conferences, and gray literature were searched in 2013 and 2018. Nearly all studies identified (60) were conducted between 2007 and 2018. Data from 40 of the 60 studies were included in the meta-analysis, which accounted for a total of 10,871 paired dried blood spot:plasma data points. We used random effects models to determine the bias, accuracy, precision, and misclassification for each viral load technology and to account for between-study variation. Dried blood spot specimens produced consistently higher mean viral loads across all technologies when compared to plasma specimens. However, when used to identify treatment failure, each technology compared best to plasma at a threshold of 1,000 copies/ml, the present World Health Organization recommended treatment failure threshold. Some heterogeneity existed between technologies; however, 5 technologies had a sensitivity greater than 95%. Furthermore, 5 technologies had a specificity greater than 85% yet 2 technologies had a specificity less than 60% using a treatment failure threshold of 1,000 copies/ml. The study's main limitation was the direct applicability of findings as nearly all studies to date used dried blood spot samples prepared in laboratories using precision pipetting that resulted in consistent input volumes. CONCLUSIONS: This analysis provides evidence to support the implementation and scale-up of dried blood spot specimens for viral load testing using the same 1,000 copies/ml treatment failure threshold as used with plasma specimens. This may support improved access to viral load testing in resource-limited settings lacking the required infrastructure and cold chain storage for testing with plasma specimens.
Asunto(s)
Infecciones por VIH , VIH-1 , Pruebas con Sangre Seca/métodos , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , ARN Viral , Sensibilidad y Especificidad , Carga Viral/métodosRESUMEN
[This corrects the article DOI: 10.1371/journal.pmed.1002589.].
RESUMEN
BACKGROUND: Systematic reviews have described high rates of attrition in patients with HIV receiving antiretroviral therapy (ART). However, migration and clinical transfer may lead to an overestimation of attrition (death and loss to follow-up). Using a newly linked national laboratory database in South Africa, we assessed national retention in South Africa's national HIV program. METHODS AND FINDINGS: Patients receiving care in South Africa's national HIV program are monitored through regular CD4 count and viral load testing. South Africa's National Health Laboratory Service has maintained a database of all public-sector CD4 count and viral load results since 2004. We linked individual laboratory results to patients using probabilistic matching techniques, creating a national HIV cohort. Validation of our approach in comparison to a manually matched dataset showed 9.0% undermatching and 9.5% overmatching. We analyzed data on patients initiating ART in the public sector from April 1, 2004, to December 31, 2006, when ART initiation could be determined based on first viral load among those whose treatment followed guidelines. Attrition occurred on the date of a patient's last observed laboratory measure, allowing patients to exit and reenter care prior to that date. All patients had 6 potential years of follow-up, with an additional 2 years to have a final laboratory measurement to be retained at 6 years. Data were censored at December 31, 2012. We assessed (a) national retention including all laboratory tests regardless of testing facility and (b) initiating facility retention, where laboratory tests at other facilities were ignored. We followed 55,836 patients initiating ART between 2004 and 2006. At ART initiation, median age was 36 years (IQR: 30-43), median CD4 count was 150 cells/mm3 (IQR: 81-230), and 66.7% were female. Six-year initiating clinic retention was 29.1% (95% CI: 28.7%-29.5%). After allowing for transfers, national 6-year retention was 63.3% (95% CI: 62.9%-63.7%). Results differed little when tightening or relaxing matching procedures. We found strong differences in retention by province, ranging from 74.2% (95% CI: 73.2%-75.2%) in Western Cape to 52.2% (95% CI: 50.6%-53.7%) in Mpumalanga at 6 years. National attrition was higher among patients initiating at lower CD4 counts and higher viral loads, and among patients initiating ART at larger facilities. The study's main limitation is lack of perfect cohort matching, which may lead to over- or underestimation of retention. We also did not have data from KwaZulu-Natal province prior to 2010. CONCLUSIONS: In this study, HIV care retention was substantially higher when viewed from a national perspective than from a facility perspective. Our results suggest that traditional clinical cohorts underestimate retention.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Transferencia de Pacientes/estadística & datos numéricos , Atención Primaria de Salud/métodos , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricos , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sudáfrica , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The AIDS Clinical Trials Group (ACTG) A5230 study evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure (VF) on first-line human immunodeficiency virus (HIV) regimens in Africa and Asia. METHODS: Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200 000 copies/mL. All subjects received LPV/r 400/100 mg twice daily. VF was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200 mg/tenofovir 300 mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models. RESULTS: One hundred twenty-three subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 of 123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39 of 41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400 copies/mL over 104 weeks on LPV/r monotherapy was 60% (95% CI, 50%-68%); 80%-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level <400 copies/mL at weeks 24, 48, and 104 revealed that 61%, 62%, and 65% were suppressed to <40 copies/mL, respectively. CONCLUSIONS: LPV/r monotherapy after first-line VF with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks. CLINICAL TRIALS REGISTRATION: NCT00357552.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antivirales/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Adulto , África , Asia , Países en Desarrollo , Quimioterapia/métodos , Femenino , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Plasma/virología , ARN Viral/sangre , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. METHODS: We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. RESULTS: We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. CONCLUSIONS: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).
Asunto(s)
Adenina/análogos & derivados , Antirretrovirales/uso terapéutico , Desoxicitidina/análogos & derivados , Infecciones por VIH/prevención & control , VIH-1 , Organofosfonatos/uso terapéutico , Adenina/efectos adversos , Adenina/uso terapéutico , Adolescente , Adulto , Antirretrovirales/efectos adversos , Conducta Anticonceptiva/estadística & datos numéricos , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Método Doble Ciego , Combinación de Medicamentos , Farmacorresistencia Viral , Emtricitabina , Femenino , Infecciones por VIH/epidemiología , Seropositividad para VIH , VIH-1/genética , VIH-1/aislamiento & purificación , Heterosexualidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Embarazo , ARN Viral/sangre , Conducta Sexual/estadística & datos numéricos , Tenofovir , Adulto JovenRESUMEN
In recent years, there has been significant investment from both the private and public sectors in the development of diagnostic technologies to meet the need for human immunodeficiency virus (HIV) and tuberculosis testing in low-resource settings. Future investments should ensure that the most appropriate technologies are adopted in settings where they will have a sustainable impact. Achieving these aims requires the involvement of many stakeholders, as their needs, operational constraints, and priorities are often distinct. Here, we discuss these considerations from different perspectives representing those of various stakeholders involved in the development, introduction, and implementation of diagnostic tests. We also discuss some opportunities to address these considerations.
Asunto(s)
Infecciones por VIH/diagnóstico , Sistemas de Atención de Punto/tendencias , Tuberculosis/diagnóstico , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/uso terapéutico , Técnicas Bacteriológicas/métodos , Infecciones por VIH/tratamiento farmacológico , Política de Salud , Humanos , PobrezaRESUMEN
Little is known about the effect of human immunodeficiency virus type 1 (HIV-1) resistance mutations present at time of regimen switch on the response to second-line antiretroviral therapy in Africa. In adults who switched to boosted protease inhibitor-based regimens after first-line failure, HIV-RNA and genotypic resistance testing was performed at switch and after 12 months. Factors associated with treatment failure were assessed using logistic regression. Of 243 participants, 53% were predicted to receive partially active second-line regimens due to drug resistance. The risk of treatment failure was, however, not increased in these participants. In this African cohort, boosted protease inhibitors successfully resuppressed drug-resistant HIV after first-line failure.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Terapia Recuperativa/métodos , Carga Viral , Adulto , África del Sur del Sahara , Estudios de Cohortes , Farmacorresistencia Viral , Femenino , VIH-1/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Estudios Prospectivos , ARN Viral/sangre , ARN Viral/genética , Resultado del TratamientoRESUMEN
The development, evaluation, and implementation of new and improved diagnostics have been identified as critical needs by human immunodeficiency virus (HIV) and tuberculosis researchers and clinicians alike. These needs exist in international and domestic settings and in adult and pediatric populations. Experts in tuberculosis and HIV care, researchers, healthcare providers, public health experts, and industry representatives, as well as representatives of pertinent US federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health, United States Agency for International Development) assembled at a workshop proposed by the Diagnostics Working Group of the Federal Tuberculosis Taskforce to review the state of tuberculosis diagnostics development in adult and pediatric populations.
Asunto(s)
Investigación Biomédica/métodos , Tuberculosis/diagnóstico , Técnicas Bacteriológicas/economía , Técnicas Bacteriológicas/métodos , Investigación Biomédica/economía , HumanosRESUMEN
Background: Mycobacterium tuberculosis complex (MTBC) isolates are typically stored at -70 °C in cryovials containing 1 mL aliquots of a liquid medium, with or without 50% glycerol. Multiple uses of the culture stock may decrease the strain viability while increasing the risk of culture contamination. Small culture aliquots may be more practical; however, storage capacity remains challenging. MicrobankTM beads (25 beads/vial) for the long-term storage of fungal cultures is well documented, but their use for storing MTBC isolates is uninvestigated. Objective: The study aimed to determine the feasibility of using MicrobankTM beads for long-term storage of MTBC isolates at a laboratory in South Africa. Methods: In February 2020, 20 isolates in liquid culture were stored in MicrobankTM beads, following an in-house developed protocol, at -70 °C. At defined time points (16 months [15 June 2021] and 21 months [18 November 2021]), two beads were retrieved from each storage vial and assessed for viability and level of contamination. Results: Stored liquid isolates demonstrated MTBC growth within an average time-to-detection of 18 days following retrieval, even at 21 months post storage. Contaminating organisms were detected in 2 of 80 (2.5%) culture isolates. Conclusion: MicrobankTM beads will allow for the reculture of up to 25 culture isolates using a reduced culture volume compared to current storage methods. MicrobankTM beads represent a storage solution for the medium-term storage of MTBC isolates. What this study adds: This study evaluated the use of MicrobankTM beads as an alternate method for storing MTBC culture isolates at -70 °C and provided a suitable option for medium-term storage of MTBC.
RESUMEN
Background: South Africa has the largest HIV epidemic globally, with ~7.5 million people living with HIV in 2021. Adolescent girls (AG) and young women (YW), aged 15-19 years and 20-24 years, are twice as likely to be living with HIV as their male counterparts. The national HIV prevalence for young women was 9.1% (2021), with limited data on disease severity. Objectives: This study assessed very advanced HIV disease (CD4 < 100 cells/µL) in adolescent girls and young women (AGYW) in South Africa. Method: A retrospective descriptive study analysed data collated from the National Health Laboratory Service database for 2017 to 2021 calendar years for AGYW. National and provincial specimen volumes, the percentage of tests with a CD4 < 100 cells/µL and ≥ 100 cells/µL, and the median and interquartile ranges, were calculated. Logistic regression determined the odds ratio for a CD4 < 100 cells/µL, controlling for age category. Results: Data for 1 199 010 CD4 specimens indicated a significant decrease in volumes of 34% from 287 410 (2017) to 189 533 (2021). The percentage of samples with a count < 100 cells/µL ranged from 4.9% to 5.2% for YW versus 5.6% to 6.1% for AG. Provincial data for a CD4 count < 100 cells/µL ranged between 4.5% and 8.3% in AG and 3.6% to 6.3% for YW. Logistic regression indicated a 24% higher likelihood for AG having a CD4 count < 100 cells/µL. Conclusion: The study reported a higher proportion of very advanced HIV disease for AG versus YW nationally, with provincial disparity needing further analysis.
RESUMEN
Human migration facilitates the spread of infectious disease. However, little is known about the contribution of migration to the spread of tuberculosis in South Africa. We analyzed longitudinal data on all tuberculosis test results recorded by South Africa's National Health Laboratory Service (NHLS), January 2011-July 2017, alongside municipality-level migration flows estimated from the 2016 South African Community Survey. We first assessed migration patterns in people with laboratory-diagnosed tuberculosis and analyzed demographic predictors. We then quantified the impact of cross-municipality migration on tuberculosis incidence in municipality-level regression models. The NHLS database included 921,888 patients with multiple clinic visits with TB tests. Of these, 147,513 (16%) had tests in different municipalities. The median (IQR) distance travelled was 304 (163 to 536) km. Migration was most common at ages 20-39 years and rates were similar for men and women. In municipality-level regression models, each 1% increase in migration-adjusted tuberculosis prevalence was associated with a 0.47% (95% CI: 0.03% to 0.90%) increase in the incidence of drug-susceptible tuberculosis two years later, even after controlling for baseline prevalence. Similar results were found for rifampicin-resistant tuberculosis. Accounting for migration improved our ability to predict future incidence of tuberculosis.
Asunto(s)
Infecciones por VIH , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Sudáfrica/epidemiología , Ciudades , Tuberculosis/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Encuestas y Cuestionarios , Infecciones por VIH/epidemiologíaRESUMEN
The National Health Laboratory Service (NHLS) collects all public health laboratory test results in South Africa, providing a cohort from which to identify groups, by age, sex, HIV, and viral suppression status, that would benefit from increased tuberculosis (TB) testing. Using NHLS data (2012-2016), we assessed levels and trends over time in TB diagnostic tests performed (count and per capita) and TB test positivity. Estimates were stratified by HIV status, viral suppression, age, sex, and province. We used logistic regression to estimate the odds of testing positive for TB by viral suppression status. Nineteen million TB diagnostic tests were conducted during period 2012-2016. Testing per capita was lower among PLHIV with viral suppression than those with unsuppressed HIV (0.08 vs 0.32) but lowest among people without HIV (0.03). Test positivity was highest among young adults (aged 15-35 years), males of all age groups, and people with unsuppressed HIV. Test positivity was higher for males without laboratory evidence of HIV than those with HIV viral suppression, despite similar individual odds of TB. Our results are an important national baseline characterizing who received TB testing in South Africa. People without evidence of HIV, young adults, and males would benefit from increased TB screening given their lower testing rates and higher test positivity. These high-test positivity groups can be used to guide future expansions of TB screening.
Asunto(s)
Infecciones por VIH , Tuberculosis , Masculino , Adulto Joven , Humanos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Sudáfrica/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tamizaje Masivo , Modelos LogísticosRESUMEN
BACKGROUND: It is not known how often mutations in the connection and ribonuclease H domains of reverse transcriptase (RT) emerge with failure of first-line antiretroviral therapy (ART) in subtype C human immunodeficiency virus type 1 (HIV-1) infection and how these mutations affect susceptibility to other antiretrovirals. METHODS: We compared full-length RT sequences in plasma obtained before therapy and at virologic failure of initial ART among 63 participants with subtype C HIV-1 infection enrolled in the Comprehensive International Program of Research on AIDS in South Africa (CIPRA-SA) study. Recombinant viruses containing full-length plasma-derived RT sequences from participants with N348I at virologic failure were assayed for drug susceptibility. RESULTS: Y181C and M184V mutations in the RT polymerase domain were associated with failure of stavudine-lamivudine-nevirapine (d4T/3TC/NVP; P < .01), and K103N, V106M, and M184V with failure of d4T/3TC/efavirenz (EFV; P < .01). N348I in the RT connection domain emerged in 45% (P = .002) and 12% (P = .06) of participants receiving failing regimens containing NVP or EFV, respectively. Longitudinal analyses revealed that nonnucleoside RT inhibitor resistance mutations in the polymerase domain generally appeared first. N348I emerged at the same time, or after, M184V. N348I in the context of polymerase domain mutations reduced susceptibility to NVP (8.9-13-fold), EFV (4-56-fold), etravirine (ETV; 1.9-4.7-fold) and decreased hypersusceptibility to zidovudine (AZT; 1.4-2.2-fold). CONCLUSIONS: N348I emerges frequently with virologic failure of first-line ART in subtype C HIV-1 infection and reduces susceptibility to NVP, EFV, ETV, and AZT. Additional studies are warranted to characterize the effects of N348I on virologic response to second- and third-line regimens in resource-limited settings where subtype C predominates.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Transcriptasa Inversa del VIH/genética , VIH-1/enzimología , Inhibidores de la Transcriptasa Inversa/farmacología , Farmacorresistencia Viral , VIH-1/genética , Humanos , Mutación , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Insuficiencia del Tratamiento , Carga ViralRESUMEN
The PharmAccess African Studies to Evaluate Resistance (PASER) network was established as a collaborative partnership of clinical sites, laboratories, and research groups in 6 African countries; its purpose is to build research and laboratory capacity in support of a coordinated effort to assess population-level acquired and transmitted human immunodeficiency virus type-1 drug resistance (HIVDR), thus contributing to the goals of the World Health Organization Global HIV Drug Resistance Network. PASER disseminates information to medical professionals and policy makers and conducts observational research related to HIVDR. The sustainability of the network is challenged by funding limitations, constraints in human resources, a vulnerable general health infrastructure, and high cost and complexity of molecular diagnostic testing. This report highlights experiences and challenges in the PASER network from 2006 to 2010.
Asunto(s)
Fármacos Anti-VIH/farmacología , Creación de Capacidad , Infecciones por VIH/tratamiento farmacológico , Vigilancia de la Población , Administración en Salud Pública , África , Países en Desarrollo , Farmacorresistencia Viral , Humanos , Organización Mundial de la SaludRESUMEN
Human immunodeficiency virus (HIV) RNA testing and HIV drug resistance (HIVDR) testing are not routinely available for therapeutic monitoring of patients receiving antiretroviral therapy (ART) in resource-limited settings. World Health Organization HIVDR early warning indicators (EWIs) assess ART site factors known to favor the emergence of HIVDR. HIV drug resistance EWI monitoring was performed within the PharmAccess African Studies to Evaluate Resistance Monitoring (PASER-M) study, comprising 13 ART sites in 6 African countries. Early warning indicator assessment in the PASER network identified vulnerable aspects of ART programs and triggered interventions aimed at minimizing HIVDR emergence. Additionally, data suggest an advantage of medication possession ratio over on-time antiretroviral drug pickup in identifying patients at risk for HIVDR development.
Asunto(s)
Antirretrovirales/farmacología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Cumplimiento de la Medicación/estadística & datos numéricos , África del Sur del Sahara/epidemiología , Antirretrovirales/uso terapéutico , Estudios de Cohortes , Atención a la Salud , Farmacorresistencia Viral , Indicadores de Salud , Humanos , Perdida de Seguimiento , Vigilancia de la Población , Sensibilidad y Especificidad , Organización Mundial de la SaludRESUMEN
BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African countries and predicted their impact on second-line drug susceptibility. METHODS: A total of 2588 antiretroviral-naive individuals initiated ART consisting of different nucleoside reverse transcriptase inhibitor (NRTI) backbones (zidovudine, stavudine, tenofovir, or abacavir, plus lamivudine or emtricitabine) with either efavirenz or nevirapine. Population sequencing after 12 months of ART was retrospectively performed if HIV RNA was >1000 copies/mL. The 2010 International Antiviral Society-USA list was used to score major DRMs. The Stanford algorithm was used to predict drug susceptibility. RESULTS: HIV-1 sequences were generated for 142 participants who virologically failed ART, of whom 70% carried ≥1 DRM and 49% had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1-8). The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with ≥1 DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for tenofovir, in 18% for stavudine, and in 10% for zidovudine. CONCLUSIONS: Early failure detection limited the accumulation of resistance. After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART. Strategies to prevent HIV-1 resistance are a global priority.
Asunto(s)
Antirretrovirales/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Adulto , África del Sur del Sahara , Antirretrovirales/farmacología , Estudios de Cohortes , Femenino , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación Missense , Análisis de Secuencia de ADN , Insuficiencia del TratamientoRESUMEN
OBJECTIVE: The World Health Organization recommends using Xpert MTB/RIF for diagnosis of pulmonary tuberculosis (PTB), but there is little evidence on the optimal placement of Xpert instruments in public health systems. We used recent South African data to compare the cost of placing Xpert at points of TB treatment (all primary clinics and hospitals) with the cost of placement at sub-district laboratories. METHODS: We estimated Xpert's cost/test in a primary clinic pilot and in the pilot phase of the national Xpert roll-out to smear microscopy laboratories; the expected future volumes for each of 223 laboratories or 3799 points of treatment; the number and cost of Xpert instruments required and the national cost of using Xpert for PTB diagnosis for each placement scenario in 2014. RESULTS: In 2014, South Africa will test 2.6 million TB suspects. Laboratory placement requires 274 Xpert instruments, while point-of-treatment placement requires 4020 instruments. With an Xpert cartridge price of $14.00, the cost/test is $26.54 for laboratory placement and $38.91 for point-of-treatment placement. Low test volumes and a high number of sites are the major contributors to higher point-of-treatment costs. National placement of Xpert at laboratories would cost $71 million/year; point-of-treatment placement would cost $107 million/year, 51% more. CONCLUSION: Placing Xpert technology at points of treatment is substantially more expensive than placing the instruments in smear microscopy laboratories. The incremental benefits of point-of-treatment placement, in terms of better patient outcomes, will have to be equally substantial to justify the additional cost to the national health budget.
Asunto(s)
Equipo para Diagnóstico/economía , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Costos y Análisis de Costo , Humanos , Sudáfrica , Tuberculosis Resistente a Múltiples Medicamentos/diagnósticoRESUMEN
BACKGROUND: As HIV-infected infants have high mortality, the World Health Organization now recommends initiating antiretroviral therapy as early as possible in the first year of life. However, in many settings, laboratory diagnosis of HIV in infants is not readily available. We aimed to develop a clinical algorithm for HIV presumptive diagnosis in infants < 10 weeks old using screening data from the Children with HIV Early Antiretroviral therapy (CHER) study in South Africa.HIV-infected and HIV-uninfected exposed infants < 10 weeks of age were identified through Vertical Transmission Prevention programs. Clinical and laboratory data were systematically recorded, groups were compared using Kruskal-Wallis, analysis of variance (ANOVA), and Fisher's exact tests. Receiver Operating Characteristic (ROC) curves were compiled using combinations of clinical findings. RESULTS: 417 HIV-infected and 125 HIV-exposed, uninfected infants, median age 46 days (IQR 38-55), were included. The median CD4 percentage in HIV-infected infants was 34 (IQR 28-41)%. HIV-infected infants had lower weight-for-age, more lymphadenopathy, oral thrush, and hepatomegaly than exposed uninfected infants (Adjusted Odds Ratio 0.51, 8.8, 5.6 and 23.5 respectively; p < 0.001 for all). Sensitivity of individual signs was low (< 20%) but specificity high (98-100%). If any one of oral thrush, hepatomegaly, splenomegaly, lymphadenopathy, diaper dermatitis, weight < 50(th) centile are present, sensitivity for HIV infection amongst HIV-exposed infants was 86%. These algorithms performed similarly when used to predict severe immune suppression. CONCLUSIONS: A combination of physical findings is helpful in identifying infants most likely to be HIV-infected. This may inform management algorithms and provide guidance for focused laboratory testing in some settings, and should be further validated in these settings and elsewhere.
Asunto(s)
ADN Viral/análisis , Infecciones por VIH/diagnóstico , VIH-1 , Examen Físico/estadística & datos numéricos , Reacción en Cadena de la Polimerasa/estadística & datos numéricos , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Peso Corporal , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Infecciones por VIH/epidemiología , Humanos , Lactante , Masculino , Estudios Prospectivos , Factores de Riesgo , Sudáfrica/epidemiologíaRESUMEN
The South African antiretroviral treatment guidelines recommend the use of human immunodeficiency virus type 1 (HIV-1) load testing for patient monitoring and, in particular, to assist in switching to second-line treatment regimens. There are significant challenges to implementing HIV load testing on the scale that is required in South Africa. To put this in context, approximately 560,000 HIV-infected individuals are receiving antiretroviral therapy, and program recommendations include viral load testing twice per year. Currently, a 3-tiered laboratory infrastructure exists with tertiary facilities and, to some extent, secondary laboratories able to implement quantitative HIV nucleic acid testing. Challenges include high sample volumes, transportation logistics from remote sites, costs, phlebotomy in children, a national skills shortage, and sample throughput of technology platforms. Several approaches are thus being explored simultaneously: (1) the feasibility of establishing higher throughput and more automated central laboratories; (2) improvement of current sample collection, transportation, and storage techniques; (3) alternative viral load technologies, including flow-based marker screening approaches to reduce testing volumes, and (4) point-of-care viral load testing strategies for clinics. The development of appropriate solutions for each laboratory tier in South Africa will require close collaboration between researchers in the field and partners in industry.
Asunto(s)
Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Ciencia del Laboratorio Clínico/organización & administración , Carga Viral/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , SudáfricaRESUMEN
There is increasing evidence to support the inability of CD4 cell count monitoring to predict virological failure in human immunodeficiency virus-infected individuals receiving antiretroviral therapy. There is renewed interest in improving access to viral load monitoring in resource-constrained regions to monitor adherence to treatment and to switch therapy. The field is rapidly changing as new technology platforms are made available for evaluation. This article presents an up to date summary of the assays available for viral load monitoring and suggests approaches for their implementation.