Routine Viral Load Testing Research Articles

Leveraging routine viral load testing to integrate diabetes screening among patients on antiretroviral therapy in Malawi.

BackgroundPeople living with HIV are at an increased risk of diabetes mellitus due to HIV infection and exposure to antiretroviral therapy (ART). Despite this, integrated diabetes screening has not been implemented commonly in African HIV clinics. Our objective was to explore the feasibility of integrating diabetes screening into existing routine HIV viral load (VL) monitoring and to determine a group of HIV patients that benefit from a targeted screening for diabetes.MethodsA mixed methods study was conducted from January to July 2018 among patients on ART aged≥18 y and healthcare workers at an urban HIV clinic in Zomba Central Hospital, Malawi. Patients who were due for routine VL monitoring underwent a finger-prick for simultaneous point-of-care glucose measurement and dried blood spot sampling for a VL test. Diabetes was diagnosed according to WHO criteria. We collected demographic and medical history information using an interviewer-administered questionnaire and electronic medical records. We conducted focus group discussions among healthcare workers about their experience and perceptions regarding the integrated diabetes screening program.ResultsOf patients undergoing routine VL monitoring, 1316 of 1385 (95%) had simultaneous screening for diabetes during the study period. The median age was 44 y (IQR: 38–53); 61% were female; 28% overweight or obese; and median ART duration was 83 mo (IQR: 48–115). At baseline, median CD4 count was 199 cells/mm3 (IQR: 102–277) and 50% were in WHO clinical stages I or II; 45% were previously exposed to stavudine and 88% were virologically suppressed (<1000 copies/mL). Diabetes prevalence was 31/1316 (2.4%). Diabetes diagnosis was associated with age ≥40 y (adjusted OR [aOR] 7.44; 95% CI: 1.74 to 31.80), being overweight and/or obese (aOR 2.46; 95% CI: 1.13 to 5.38) and being on a protease inhibitor-based ART regimen (aOR 5.78; 95% CI: 2.30 to 14.50). Healthcare workers appreciated integrated diabetes screening but also reported challenges including increased waiting time, additional workload and inadequate communication of results to patients.ConclusionsIntegrating diabetes screening with routine VL monitoring (every 2 y) seems feasible and was valued by healthcare workers. The additional cost of adding diabetes screening into VL clinics requires further study and could benefit from a targeted approach prioritizing patients aged ≥40 y, being overweight/obese and on protease inhibitor-based regimens.

High levels of viral repression, malnutrition and second-line ART use in adolescents living with HIV: a mixed methods study from Myanmar

BackgroundAdolescents living with HIV/AIDS (ALHIV) are a particularly vulnerable but often overlooked group in the HIV response despite additional disease management challenges.MethodsAll ALHIV (10–19 years), on ART for ≥6 months, presenting to care at a Médecins Sans Frontières (MSF) clinic in Myanmar from January–April 2016 were eligible for the quantitative study component (clinical history, medical examination, laboratory investigation). A subset of these respondents were invited to participate in qualitative interviews. Interviews and focus groups were also conducted with other key informants (care givers, clinicians).ResultsOf 177 ALHIV, 56% (100) were aged 9–13 years and 77 (44%) were 14–19. 49% (86) had been orphaned by one parent, and 19% (33) by both. 59% (104) were severely underweight (BMI < 16). 47% presented with advanced HIV (WHO stage III/IV). 93% were virally supressed (< 250 copies/mL). 38 (21%) of ALHIV were on a second-line ART after first-line virological failure. Qualitative interviewing highlighted factors limiting adherence and the central role that HIV counsellors play for both ALHIV patients and caregivers.ConclusionsOur study shows good clinical, immunological, and virological outcomes for a cohort of Myanmar adolescents living with HIV, despite a majority being severely underweight, presenting with Stage III or IV illness, and the prevalence of comorbid infections (TB). Many treatment and adherence challenges were articulated in qualitative interviewing but emphasized the importance of actively engaging adolescents in their treatment. Comprehensive HIV care for this population must include routine viral load testing and social support programs.

HIV viral load testing coverage and timeliness after implementation of the wellness anniversary in a paediatric and adolescent HIV clinic in KwaZulu-Natal, South Africa.

BackgroundThe UNAIDS 2020 Global strategy to reduce the transmission of HIV includes ensuring HIV viral load (VL) testing coverage of at least 90% on all patients on antiretroviral therapy (ART). Routine VL monitoring has been shown to result in earlier detection of treatment failure, timely regimen switches, promotion of adherence to treatment and improved survival. We wanted to assess the introduction of the wellness anniversary in improving routine viral load monitoring.ObjectivesWe retrospectively assessed effects of the wellness anniversary on routine VL coverage, timeliness and suppression rates.MethodThe month when the patient initiated ART was designated as the wellness anniversary. On the anniversary month a package of care, which included a routine VL, was delivered. We conducted a retrospective chart audit to assess VL coverage and timeliness between two time periods, from January 2016 to December 2016 (pre-implementation) and from January 2017 to December 2017 (post-implementation).ResultsTimeliness of VL testing improved from 27.5% in the pre-implementation cohort to 49.7% in the post-implementation cohort. Our study showed high VL testing coverage before the implementation of the wellness anniversary with an average of 98.3% VL. There was a significant correlation between timeliness and VL suppression (VLS) in the post-implementation group.ConclusionImplementation of the wellness anniversary may improve timeliness of routine VL testing in settings with high VL coverage. Studies looking at the effect of timeliness on VLS and clinical outcomes are needed.

Uptake of routine viral load testing among people living with HIV and its implementation challenges in Yangon region of Myanmar: a mixed-methods study

ObjectivesIn 2017, Myanmar implemented routine viral load (VL) monitoring for assessing the response to antiretroviral therapy (ART) among people living with HIV (PLHIV). The performance of routine VL testing and...

Quantifying pediatric patient need for second- and third-line HIV treatment: A tool for decision-making in resource-limited settings

As national HIV programs across the world mature and continue to scale up towards UNAIDS’ 90-90-90 targets, it is increasingly important to accurately estimate HIV treatment needs in pediatric patient populations to prepare for anticipated increases in demand. This is particularly vital in sub-Saharan Africa, where the bulk of the global pediatric HIV burden remains concentrated, and for treatment-experienced populations, for which data are severely limited. This article discusses the conceptual framework behind and application of a five-year country-level quantification and decision-making tool aimed at providing national HIV programs and their partners with a better understanding of their evolving national HIV treatment and programming needs for second-and third-line pediatric populations. The conceptual framework of the algorithm which undergirds the tool is the patient pathway, along which key influencing factors that determine whether pediatric HIV patients are linked to care, remain in treatment, and are appropriately switched to later lines of treatment are accounted for quantitatively. Excel-based and arithmetic, the algorithm is designed to use available national, regional, and global data for factors impacting patient estimates including treatment coverage; routine viral load testing; viral load non-suppression; confirmed treatment failure; and patient loss to follow up—outcomes for which data are generally very limited in this patient population. The ultimate output of the tool is an estimate of the aggregate annual number of patients by treatment line. Given the limitations in available data for pediatric HIV, particularly for patients on second- and third-line treatments, this tool may help fill a data gap by providing a mechanism for policymakers to scenario plan, thus aiding resource allocation decisions for pediatric HIV program scale-up. The tool may be used to streamline national antiretroviral procurement of later lines of treatment, especially in resource-limited settings, and may also be used to add value to broader HIV policy and planning processes at the national level.

Virologic failure and switch to second-line antiretroviral therapy in children with HIV in Lilongwe, Malawi: an observational cohort study.

As routine viral load testing among HIV-infected individuals on antiretroviral therapy (ART) expands, virologic failure (VF) among children in developing countries remains poorly understood. We assessed the rate of VF, the proportion failing who were subsequently switched to second-line ART and factors associated with VF among children ≤18y. An observation cohort study among 1312 children at two public clinics in Lilongwe, Malawi who initiated a first-line ART regimen between January 2014 and December 2017 and remained on treatment for ≥6mo was conducted. Kaplan-Meier methods estimated the probabilities of VF. Univariable and multivariable Poisson regression models were used to explore predictors of VF. Overall, 16% (208/1312) of children experienced VF with an incidence rate of 10.1 events per 100 person-years. Of the 208, 184 (88%) were switched to second-line ART: 68 (43%) switched the same day VF was confirmed and 106 (66%) switched within 90d of confirmed VF. Use of a Nevirapine (NVP)-based regimen and initiating ART in 2016-2017 compared with 2014-2015 were independent predictors of VF. VF is common among children receiving ART. The findings suggest that VF can be reduced by phasing out NVP-based regimen and by ensuring optimal adherence to ART.

Accurate dried blood spots collection in the community using non-medically trained personnel could support scaling up routine viral load testing in resource limited settings.

Regular plasma HIV-RNA testing for persons living with HIV on antiretroviral therapy (ART) is now the global standard, but as many as 60% of persons in Africa today on ART do not have access to standard laboratory HIV-RNA assays. As a result, patients in Zambia often receive treatment without any means of determining true virologic failure, which poses a risk of premature switch of ART regimens and widespread HIV drug resistance. Dry blood spots (DBS) on the other hand require unskilled personnel and less complex storage supply chain so are ideal to capture viral-load results from HIV patients outside clinic settings. We assess collection of DBS in the community using non-medically trained personnel (NMP) and documented challenges. We trained 23 NMP to collect DBS from lost to follow-up (LTFU) patients in 4 rural and urban Zambian districts. We developed a phlebotomy box to transport DBS without contamination at ambient temperature and concomitant training and standard operating procedures. We evaluated this through field observations, bi-weekly meetings, reports, and staff meetings. The laboratory assessed DBS quality for testing validity. We attempted to collect DBS from 357 participants in the community. Though individual reasons for refusal from the remaining 37% were not collected, NMPs reported privacy concerns, awkward box-size which drew attention in the community and fears of undisclosed uses of samples related to witchcraft and circulating narratives about past research. Successful DBS collection was not associated with patient gender, age, time on ART, enrolment CD4, facility. DBS viral-load collection by NMP is feasible in Zambia. Our training approach and assessments of NMP not part of the health system can be extended to patients by giving them more responsibility to manage their own differentiated care groups. Concerted efforts that compare collection of DBS by NMP to those collected by skilled-medical personnel are needed.

Results of Baseline Assessments of Two Viral Load and Early Infant Diagnosis Laboratories in Gaza Province, Mozambique

Abstract Following the WHO 2013 recommendations for routine HIV viral load (VL) testing as the tool to monitor antiretroviral therapy, countries have prepared for massive testing scale-up. However, developing countries that also bear the highest HIV prevalence often lack qualified human resources and basic infrastructure. Mozambique has established 13 VL laboratories, including 2 in the province with the highest overall HIV prevalence, Gaza. The challenges to VL testing implementation and this rapid scale-up demand an urgent investment toward laboratory accreditation to ensure accurate and reliable VL results. To identify gaps and areas for improvement where additional resources may be needed to provide high-quality VL testing services, the CDC developed a VL and Early Infant Diagnosis (EID) scorecard (106 points; 5 levels). The scorecard evaluates 9 key areas, including (1) Personnel, (2) Facility/Environment, (3) Safety, (4) Procurement/Inventory, (5) Sample Management, (6) Equipment, (7) Process Control, (8) M&amp;E Documents and Records, and (9) Internal Quality Audits/Quality Indicators. These 9 essential areas cover the pretesting, testing, and posttesting phases along the continuum of care for HIV patients. Baseline assessments in the two VL and EID laboratories in Gaza Province, Carmelo Molecular Laboratory and Xai-Xai Molecular Laboratory, were recently conducted. Personnel standards and M&amp;E documentation represented strengths across both laboratories, with over 70% of the master list of M&amp;E documents having been developed and in use. The overall gaps identified included poor segregation and prioritization of higher VL results (&gt;1,000 cp/mL), lack of internal audits, and no follow-up of nonconformities. Both laboratories scored in the level 2 range, with a total of 68 points (Carmelo) and 78 points (Xai-Xai). Considering this is a baseline assessment, we conclude that both labs are on an excellent path toward accreditation; however, additional laboratory quality mentorship is needed in order to reach accreditation standards.

Monitoring viral load for the last mile: what will it cost?

IntroductionRoutine viral load testing is the WHO‐recommended method for monitoring HIV‐infected patients on ART, and many countries are rapidly scaling up testing capacity at centralized laboratories. Providing testing access to the most remote populations and facilities (the “last mile”) is especially challenging. Using a geospatial optimization model, we estimated the incremental costs of accessing the most remote 20% of patients in Zambia by expanding the transportation network required to bring blood samples from ART clinics to centralized laboratories and return results to clinics.MethodsThe model first optimized a sample transportation network (STN) that can transport 80% of anticipated sample volumes to centralized viral load testing laboratories on a daily or weekly basis, in line with Zambia's 2020 targets. Data incorporated into the model included the location and infrastructure of all health facilities providing ART, location of laboratories, measured distances and drive times between the two, expected future viral load demand by health facility, and local cost estimates. We then continued to expand the modelled STN in 5% increments until 100% of all samples could be collected.Results and DiscussionThe cost per viral load test when reaching 80% patient volumes using centralized viral load testing was a median of $18.99. With an expanded STN, the incremental cost per test rose to $20.29 for 80% to 85% and $20.52 for 85% to 90%. Above 90% coverage, the incremental cost per test increased substantially to $31.57 for 90% to 95% and $51.95 for 95% to 100%. The high numbers of kilometres driven per sample transported and large number of vehicles needed increase costs dramatically for reaching the clinics that serve the last 5% of patients.ConclusionsProviding sample transport services to the most remote clinics in low‐ and middle‐income countries is likely to be cost‐prohibitive. Other strategies are needed to reduce the cost and increase the feasibility of making viral load monitoring available to the last 10% of patients. The cost of alternative methods, such as optimal point‐of‐care viral load equipment placement and usage, dried blood/plasma spot specimen utilization, or use of drones in geographically remote facilities, should be evaluated.

Routine versus Targeted Viral Load Strategy among Patients Starting Antiretroviral in Hanoi, Vietnam.

Introduction HIV viral load (VL) testing is recommended by the WHO as the preferred method for monitoring patients on antiretroviral therapy (ART). However, evidence that routine VL (RVL) monitoring improves clinical outcomes is lacking.MethodsWe conducted a prospective, randomized controlled trial of RVL monitoring every six months versus a targeted VL (TVL) strategy (routine CD4 plus VL testing if clinical or immunological failure) in patients starting ART between April 2011 and April 2014 at Bach Mai Hospital in Hanoi. Six hundred and forty‐seven subjects were randomized to RVL (n = 305) or TVL monitoring (n = 342) and followed up for three years. Primary endpoints were death or WHO clinical Stage 4 events between six and thirty‐six months of ART and rate of virological suppression at three years.ResultsOverall, 37.1% of subjects were female, median age was 33.4 years (IQR: 29.5 to 38.6), and 47% had a CD4 count ≤100 cells/mm3 at time of ART initiation. Approximately 44% of study events (death, LTFU, withdrawal, or Stage 4 event) and 68% of deaths occurred within the first six months of ART. Among patients on ART at six months, death or Stage 4 event occurred in 3.6% of RVL and 3.9% of TVL (p = 0.823). Survival analysis showed no significant difference between the groups (p = 0.825). Viral suppression at 36 months of ART was 97.2% in RVL and 98.9% in TVL (p = 0.206) at a threshold of 400 copies/mL and was 98.0% in RVL and 98.9% in TVL (p = 0.488) at 1000 copies/mL. In ITT analysis, 20.7% in RVL and 21.9% in TVL (p = 0.693) were unsuppressed at 1000 copies/mL.ConclusionsWe found no significant difference in rates of death or Stage 4 events and virological failure in patients with RVL monitoring compared to those monitored with a TVL strategy after three years of follow‐up. Viral suppression rates were high overall and there were few study events among patients alive and on ART after six months, limiting the study's power to detect a difference among study arms. Nonetheless, these data suggest that the choice of VL monitoring strategy may have less impact on patient outcomes compared to efforts to reduce early mortality and improve ART retention.

How accurately do routinely reported HIV viral load suppression proportions reflect progress towards the 90-90-90 target in the population on antiretroviral treatment in Khayelitsha, South Africa?

The Joint United Nations Programme on HIV/AIDS (UNAIDS) third 90-90-90 target requires 90% of patients on antiretroviral treatment (ART) to be virally suppressed (&lt;1 000 copies/mL). In Khayelitsha, Cape Town, South Africa viral load (VL) suppression of &lt;400 copies/mL was reported as 89% in 2016, but only 56% of patients had a result recorded in routine data. We conceived a VL 'cascade' to represent the steps required for an expected VL to be reported as complete in routine data and thus contribute to reported VL suppression: among those for whom a VL is 'expected', a sample must be collected and tested ('done'), a result must be 'filed' in the patient folder, 'noted' by a clinician and electronically 'captured'. The low reported completion suggested gaps along the VL cascade and cast doubt on the validity of reported suppression. To assess the validity of routinely reported VL suppression and identify barriers to VL completion. A retrospective cohort study between 1 July 2015 and 30 June 2016, which included all Khayelitsha patients receiving ART, with a routine VL expected, was conducted. We obtained data routinely captured on site and VL data from the laboratory system. A sample of 1 035 patient folders was reviewed. VL suppression was calculated using laboratory data, including all tests done, and compared with reported suppression based on on-site captured electronic data. Successful progression through each step on the VL cascade was estimated. We used logistic regression to identify factors associated with laboratory data and reported VL testing. Of 22 991 patients for whom a routine VL test was due, 84% were done, 79% filed, 76% noted and 55% captured. Using all laboratory data, VL suppression was estimated as 82%, 87%, 89% and 91% at the 50, 200, 400 and 1 000 copies/mL thresholds, respectively, but reported suppression using captured results was 80%, 86%, 88% and 89% at those thresholds. Routine VL testing is more likely to be done in children &lt;15 years old (adjusted odds ratio (aOR) 1.89, 95% confidence interval (CI) 1.45 - 2.48) and pregnant women (aOR 1.90, 95% CI 1.28 - 2.81) than in men, adjusted for facility. Despite a low reported completion, VL testing completion was high. Reported suppression using captured data was similar to suppression calculated using all laboratory data, which provided an accurate measure of progress towards the 90-90-90 target. More work is needed to reach the 16% of patients missed by routine testing.

Community and activists demand for tenofovir/emtricitabine or lamivudine/dolutegravir and routine viral load testing

Since the beginning of the HIV epidemic, informed communities have demanded and fought for access to life-saving treatment. The last several years have seen interesting developments in this area - particularly with respect to the switch to dolutegravir (DTG)-based regimens and scale-up of routine viral load testing (RVLT), and how these directly and indirectly impact issues of treatment optimization, HIV drug resistance, and sexual and reproductive health. In this review, we present recent advances in antiretroviral treatment and monitoring in the context of how treatment education and community demand for them. The latest developments with DTG and RVLT highlight underlying issues for global health systems that need to be addressed - including drug surveillance, supply chain management, and comprehensive care linkages - and the importance of community engagement in such issues. Decisions about treatment must be grounded in informed community demand, and should exist in the context of optimal care and treatment across the entire HIV cascade. Informed advocacy is essential for people living with HIV and their communities, so that they benefit from existing and future therapeutic advances. Research is needed on the importance of community demand across the HIV treatment cascade.

Adoption of routine virologic testing and predictors of virologic failure among HIV-infected children on antiretroviral treatment in western Kenya.

BackgroundAccess to routine virologic monitoring, critical to ensuring treatment success, remains limited in low- and middle-income countries. We report on implementation of routine viral load (VL) monitoring and risk factors for virologic failure among HIV-infected children on antiretroviral treatment (ART) in Western Kenya.MethodsRoutine VL testing was introduced in western Kenya in November 2013. We performed a case-control study among 1190 HIV-infected children ≤15 years on ART who underwent routine VL testing June 2014–May 2015. A random sample of 98 cases (virologic failure define as VL >1000 cps/mL) and 201 controls (VL <1000 cps/mL) from five facilities in three high HIV prevalence counties in Kenya were followed for a minimum of 12 months. Data from patient charts were analyzed using logistic regression to determine factors associated with failure to attain virologic suppression at initial routine and subsequent VL testing among cases.ResultsOverall, 1190 (94%) children with a median age of 8 years underwent routine VL testing of whom (37%) had virological failure. Among the 299 cases and controls, WHO stage, baseline CD4 count and time since ART initiation were not associated with virologic failure during the follow-up period. In multivariable analysis, unsuppressed children at initial test were more likely to be male (adjusted Odds Ratio (aOR) 2.1, 95% Confidence Interval (CI) 2.1–3.6) and have had an ART regimen change (aOR 2.0, CI 1.0–3.7) than controls. Of the two-thirds of children 201/299 who had a subsequent VL performed, VL suppression was greater among those suppressed at initial test 126/135 (93.3%) compared to children with virologic failure 15/66 (22.7%, p<0.0001). Among those failing at first test who achieved viral suppression in follow up, 12/15 (80%) were on a protease inhibitor (PI)-based regimen. In the multivariable analysis of children with subsequent VL testing, children on PI-based 2nd line regimens were 10-fold more likely to achieve viral suppression than children on first-line NNRTI-based ART (adjusted Odds Ratio [aOR] 0.1; 95%CI 0.0–0.4).ConclusionCoverage of initial routine viral load testing among children on ART in western Kenya is high. However, subsequent testing and virologic suppression are low in children with virologic failure on initial routine viral load test. There is an urgent need to improve management and viral load monitoring of children living with HIV experiencing treatment failure to ensure improved long-term outcomes.

Community-driven demand creation for the use of routine viral load testing: a model to scale up routine viral load testing.

Introduction HIV treatment outcomes are dependent on the use of viral load measurement. Despite global and national guidelines recommending the use of routine viral load testing, these policies alone have not translated into widespread implementation or sufficiently increased access for people living with HIV (PLHIV). Civil society and communities of PLHIV recognize the need to close this gap and to enable the scale up of routine viral load testing.MethodsThe International Treatment Preparedness Coalition (ITPC) developed an approach to community‐led demand creation for the use of routine viral load testing. Using this Community Demand Creation Model, implementers follow a step‐wise process to capacitate and empower communities to address their most pressing needs. This includes utlizing a specific toolkit that includes conducting a baseline assessment, developing a treatment education toolkit, organizing mobilization workshops for knowledge building, provision of small grants to support advocacy work and conducting benchmark evaluations.Results and DiscussionThe Community Demand Creation Model to increase demand for routine viral load testing services by PLHIV has been delivered in diverse contexts including in the sub‐Saharan African, Asian, Latin American and the Caribbean regions. Between December 2015 and December 2016, ITPC trained more than 240 PLHIV activists, and disbursed US$90,000 to network partners in support of their national advocacy work. The latter efforts informed a regional, community‐driven campaign calling for domestic investment in the expeditious implementation of national viral load testing guidelines.Conclusions HIV treatment education and community mobilization are critical components of demand creation for access to optimal HIV treatment, especially for the use of routine viral load testing. ITPC's Community Demand Creation Model offers a novel approach to achieving this goal.

Pretreatment HIV drug resistance results in virological failure and accumulation of additional resistance mutations in Ugandan children.

BackgroundPretreatment HIV drug resistance (PDR) can impair virological response to ART, jeopardizing effective treatment for children.MethodsChildren aged ≤12 years initiated first-line ART in Uganda during 2010–11. Baseline and 6 monthly viral load (VL) and genotypic resistance testing if VL >1000 copies/mL was done. The 2015 IAS-USA mutation list and Stanford algorithm were used to score drug resistance mutations (DRMs) and susceptibility. Virological failure (VF) was defined as two consecutive VLs >1000 copies/mL or death after 6 months of ART. Factors associated with failure and acquired drug resistance (ADR) were assessed in a logistic regression analysis.ResultsAmong 317 children enrolled, median age was 4.9 years and 91.5% received NNRTI-based regimens. PDR was detected in 47/278 (16.9%) children, of whom 22 (7.9%) had resistance against their first-line regimen and were therefore on a partially active regimen. After 24 months of follow-up, 92/287 (32.1%) had experienced VF. Children with PDR had a higher risk of VF (OR 15.25, P < 0.001) and ADR (OR 3.58, P = 0.01).ConclusionsAlmost one-third of children experienced VF within 24 months of NNRTI-based first-line treatment. PDR was the strongest predictor of VF and ADR, and therefore presents a major threat in children. There is a need for ART regimens that maximize effectiveness of first-line therapy for long-term treatment success in the presence of PDR or incorporation of routine VL testing to detect VF and change treatment in time, in order to prevent clinical deterioration and accumulation of additional drug resistance. Children ≤3 years should be initiated on a PI-based regimen as per WHO guidelines.

Comparison between Roche and Xpert in HIV-1 RNA quantitation: A high concordance between the two techniques except for a CRF02_AG subtype variant with high viral load titters detected by Roche but undetected by Xpert

BackgroundHIV-1 viral load (VL) testing is important to predict viral progression and to monitor the response to antiretroviral therapy. New HIV-1 VL tests are continuously introduced to the market. Their performance is usually compared to Abbott and/or Roche HIV-1 VL assays, as reference. The Xpert HIV-1 VL test was recently introduced, but its performance compared to Roche has not been sufficiently studied. ObjectivesTo compare the Xpert assay with Roche and to assess its use in the HIV clinical laboratory. Study designA total of 383 plasma samples of HIV-1 infected patients previously tested by Roche, were retrospectively tested by Xpert to determine concordance between the two assays. Samples included a diversity of HIV-1 subtypes and a wide range of VLs. ResultsThere was a high concordance between the two assays, except for a CRF02_AG subtype variant with high VL titters, that was detected by Roche but undetected by Xpert. The 5′ long terminal repeat gene region of this virus, targeted by the Xpert assay, was amplified and sequenced. A 25 nucleotide insert was identified, but was unmatched to any known sequences of HIV-1. This particular insert, however could not explain the false-negativity by the Xpert assay. ConclusionsThis study underlines the challenge to routine VL testing due to the high genetic diversity of HIV-1. Clinicians should, therefore be advised that a negative VL in cases where the clinical picture does not match the laboratory report, might in fact be, a false-negative result of the VL assay.

Biomarkers in Immune Reconstitution Inflammatory Syndrome (IRIS) among People Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS)

Background: An Immune Reconstitution Inflammatory Syndrome (IRIS) event is a presentation or a paradoxical worsening of a pre-existing infection following initiation of anti-retroviral therapy in the presence of a decreasing viral load and features consistent with an inflammatory process. This study was conducted to find out the significance of different clinical parameters like hemoglobin, albumin, viral load, erythrocyte, body mass index in the people living with HIV/AIDS with IRIS in Nepalese population. Methods: The study was descriptive with control group. The study included patients who experienced IRIS after initiation of highly active antiretroviral therapy (HAART) with control group as patients who were HIV positive without HAART treatment. This study was carried out on 44 HIV infected individual who initiated HAART and then suffered from IRIS and compared with 56 control HIV infected person without IRIS visiting National Public Health Laboratory (NPHL) for routine HIV viral load testing and CD4 count between April and August, 2014. Results: The patients were categorized into highly active antiretroviral therapy (HAART) naive (n=56) and on HAART with immune reconstitution inflammatory syndrome (IRIS) (n=44). Among 56 individuals naive HAART, viral load 1000 copies/ml among which 02 were female (34.83 ± 2.030 years) and 10 were male (41.34 ± 1.462 years). The comparison of CD4 count between the naive and patients enrolled for HAART; the risk of having CD4 count <200 cell/mm3 is significantly greater in male than that of female. The BMI ratio of HAART to naive patients (19.88 ± 0.7290) was lower than that of HAART enrolled patients (21.78 ± 0.3546). The hemoglobin value showed significant (P value<0.0001) difference among PLHIV having CD4 level less than 200 (9.9 ± 2.156), between 200-500 (11.63 ± 1.946) and more than 500 CD4 level (12.71 ± 1.850). Significant (P<0.0001) viral load suppression showed among HAART initiated female patients with IRIS when compared with naive female patients without IRIS. BMI, hemoglobin level, total leukocyte count, albumin level, HDL level, ESR value, CRP level and absolute eosinophil level less than 351 cells/mm3 showed significant (P<0.05) difference among HAART naive and on HAART female patients with IRIS. Significant (P<0.0001) viral load suppression showed among HAART initiated male patients with IRIS when compared with naive female patients without IRIS. BMI (18-26), hemoglobin level below 8 g/dl, TLC, serum albumin level below 5 g/dl, HDL level below 61 mg/dl, ESR level, CRP value and absolute eosinophil count showed significant (P<0.05) difference between HAART naive and on HAART male patients with IRIS. Hemoglobin level, HDL, TLC, ESR, CD8, AEC, viral load, BMI and serum albumin level showed significant (P<0.0001) difference among HAART initiated patients with IRIS when compared to different level of CD4 T cell count. Conclusion: Prevalence of anemia was high in HAART naive patients while leucopenia prevalence was higher in patients on HAART and their prevalence increased as the CD4 count decreased. HIV Patients should be investigated for hematological and immunological changes following with appropriate therapeutic interventions. The study findings reemphasize the importance of nutritional and immunological parameters to assess the stage of the disease, initiate antiretroviral therapy and monitor the response in disease progression.

Comprehensiveness of HIV care provided at global HIV treatment sites in the IeDEA consortium: 2009 and 2014.

ABSTRACT Introduction: An important determinant of the effectiveness of HIV treatment programs is the capacity of sites to implement recommended services and identify systematic changes needed to ensure that invested resources translate into improved patient outcomes. We conducted a survey in 2014 of HIV care and treatment sites in the seven regions of the International epidemiologic Database to Evaluate AIDS (IeDEA) Consortium to evaluate facility characteristics, HIV prevention, care and treatment services provided, laboratory capacity, and trends in the comprehensiveness of care compared to data obtained in the 2009 baseline survey. Methods: Clinical staff from 262 treatment sites in 45 countries in IeDEA completed a site survey from September 2014 to January 2015, including Asia-Pacific with Australia (n = 50), Latin America and the Caribbean (n = 11), North America (n = 45), Central Africa (n = 17), East Africa (n = 36), Southern Africa (n = 87), and West Africa (n = 16). For the 55 sites with complete data from both the 2009 and 2014 survey, we evaluated change in comprehensiveness of care. Results: The majority of the 262 sites (61%) offered seven essential services (ART adherence, nutritional support, PMTCT, CD4+ cell count testing, tuberculosis screening, HIV prevention, and outreach). Sites that were publicly funded (64%), cared for adults and children (68%), low or middle Human Development Index (HDI) rank (68%, 68%), and received PEPFAR support (71%) were most often fully comprehensive. CD4+ cell count testing was universally available (98%) but only 62% of clinics offered it onsite. Approximately two-thirds (69%) of sites reported routine viral load testing (44–100%), with 39% having it onsite. Laboratory capacity to monitor antiretroviral-related toxicity and diagnose opportunistic infections varied widely by testing modality and region. In the subgroup of 55 sites with two surveys, comprehensiveness of services provided significantly increased across all regions from 2009 to 2014 (5.7 to 6.5, p < 0.001). Conclusions: The availability of viral load monitoring remains suboptimal and should be a focus for site capacity, particularly in East and Southern Africa, where the majority of those initiating on ART reside. However, the comprehensiveness of care provided increased over the past 5 years and was related to type of funding received (publicly funded and PEPFAR supported).

Positive Predictive Value of the WHO Clinical and Immunologic Criteria to Predict Viral Load Failure among Adults on First, or Second-Line Antiretroviral Therapy in Kenya.

Routine HIV viral load (VL) monitoring is the standard of care for persons receiving antiretroviral therapy (ART) in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV), negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI) of these criteria to detect virologic treatment failure among patients receiving a) first-line ART, b) second/subsequent ART, and c) any regimen. Of 12,134 patient specimens tested, 2,874 (23.7%) were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2–35.7), 33.1% (95% CI 24.7–42.3) for the 40 patients on second-line/subsequent regimens, and 33.4% (95% CI 33.1–35.6) for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second-line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing.

Factors associated with HIV viral load suppression on antiretroviral therapy in Vietnam

BackgroundLimited data are available on HIV viral suppression rates among men and women on antiretroviral therapy (ART) and factors associated with HIV RNA viral load (VL) suppression in Vietnam. MethodsWe conducted a cross-sectional survey of 1255 adult patients on ART for at least 1 year across four provinces in Vietnam. Data collection included a standardised questionnaire, routine laboratory testing, and an HIV VL assay. Bivariate and logistic multivariate analyses were conducted to assess viral suppression rates and factors associated with unsuppressed HIV VL. ResultsThe median age was 34.5 years and the median time on ART was 46 months. Gender was 66% male (n=828) and 34% female (n=427). HIV viral suppression below 1000 copies/mL was 93%. Viral suppression among woman was not significantly different than among men (93.7% vs92.9%; P=0.59). On multivariate analysis, unsuppressed HIV VL was independently associated with lower CD4 cell count, social isolation, high stigma, not receiving a single-tablet daily regimen, multiple late appointments in past year, and immunological failure. ConclusionOn-treatment viral load suppression rates in Vietnam are high and already exceed the UNAIDS 90% target for viral suppression on ART. Gender does not impact viral suppression rates of patients on ART in Vietnam. Access to routine viral load testing should be improved, adherence monitoring and counselling streamlined, and ART regimens simplified to maintain viral suppression rates, as more people start ART. Psychological and social factors are also associated with unsuppressed HIV VL, necessitating treatment support interventions to address social isolation and stigma among people living with HIV in Vietnam.