Routine Viral Load Research Articles

Virological failure among HIV infected individuals on antiretroviral therapy in Pune, India: a cross-sectional study

Background: It is important to identify and manage determinants of virological failure among HIV infected individuals on treatment for achieving viral suppression. This study aimed to identify proportion and factors associated with virological failure among HIV infected individuals receiving first line antiretroviral therapy (ART).Methods: A total of 2670 adult HIV infected individuals attending ART centre at ICMR-National AIDS Research Institute, between January 2005 and June 2019 and having their recent viral load done after implementation of guidelines on routine viral load testing were included. Data were reviewed and analysed.Results: Of the 2670 people living with HIV (PLHIV) on first line antiretroviral therapy, 48% were male and 69% were more than 40 years of age. Mean baseline CD4 count at ART initiation was 252 cells/mm3 (SD:210, IQR 116-313) Overall, 13% (340/2670) of the participants showed virological failure. In multivariate analyses, participants with younger age and males retained significant association. Those with baseline CD4 counts of less than or equal to 500 cells/mm3 at treatment initiation (adjusted OR 1.71; 95% CI 1.08-2.70; p=0.022) and ART adherence ≤95% within last three months of recent viral load determination (adjusted OR 1.55, 95% CI of AOR 1.04-2.32; p=0.031) had higher risk for virological failure as compared to others. PLHIV with ART substitution due to various reasons were almost twice as likely to have virological failure (adjusted OR 1.83, 95% CI 1.44-2.33; p<0.001).Conclusions: It is crucial to focus on factors leading to virological failure among HIV infected individuals attending ART centre. Early linkage to treatment and ART initiation along with adherence counselling at every follow up visit play an important role in mitigating virological failure.

Coverage of maternal viral load monitoring during pregnancy in South Africa: Results from the 2019 national Antenatal HIV Sentinel Survey.

Objectives:South Africa has made remarkable progress in increasing the coverage of antiretroviral therapy (ART) among pregnant women; however, viral suppression among pregnant women receiving ART is reported to be low. Access to routine viral load testing is crucial to identify women with unsuppressed viral load early in pregnancy and to provide timely intervention to improve viral suppression. This study aimed to determine the coverage of maternal viral load monitoring nationally, focusing on viral load testing, documentation of viral load test results, and viral suppression (viral load < 50 copies/mL). At the time of this study, the first-line regimen for women initiating ART during pregnancy was non-nucleoside reverse transcriptase (NNRTI)-based regimen.Methods:Between 1 October and 15 November 2019, a cross-sectional survey was conducted among 15- to 49-year-old pregnant women attending antenatal care in 1589 nationally representative public health facilities. Data on ART status, viral load testing and viral load test results were extracted from medical records. Logistic regression was used to examine factors associated with coverage of viral load testing.Results:Of 8112 participants eligible for viral load testing, 81.7% received viral load testing, and 94.1% of the viral load test results were documented in the medical records. Of those who had viral load test results documented, 74.1% were virally suppressed. Women initiated on ART during pregnancy and who received ART for three months had lower coverage of viral load testing (73%) and viral suppression (56.8%) compared with women initiated on ART before pregnancy (82.8% and 76.1%, respectively). Initiating ART during pregnancy rather than before pregnancy was associated with a lower likelihood of receiving a viral load test during pregnancy (adjusted odds ratio = 1.6, 95% confidence interval: 1.4–1.8).Conclusions:Viral load result documentation was high; viral load testing could be improved especially among women initiating ART during pregnancy. The low viral suppression among women who initiated ART during pregnancy despite receiving ART for three months highlights the importance of enhanced adherence counselling during pregnancy. Our finding supports the WHO recommendation that a Dolutegravir-containing regimen be the preferred regimen for women who are newly initiating ART during pregnancy for more rapid viral suppression.

A simple noninvasive model to predict significant fibrosis in children with chronic hepatitis B.

To develop a noninvasive model to predict significant fibrosis in children with chronic hepatitis B (CHB).A total of 116 CHB pediatric patients who underwent liver biopsy were included in the study. Liver histology, which is the gold standard for assessing fibrosis, was performed. Blood routine examination, coagulation function, liver biochemistry, viral serology, and viral load were analyzed. Receiver operating characteristic curve analysis was used to analyze the sensitivity and specificity of all possible cut-off values.Based on the correlation and difference analyses, 7 available clinical parameters (total bile acid, gamma-glutamyl transpeptidase [GGT], aspartate transaminase, direct bilirubin to total bilirubin ratio, alanine aminotransferase, prealbumin [PA], and cholinesterase) were included in the modeling analysis. A model to predict significant liver fibrosis was derived using the 2 best parameters (PA and GGT). The original model was . After the mathematical calculation, the G index=600 × GGT/PA2 predicted significant fibrosis, with an area under the receiving operating characteristics (AUROC) curve of 0.733, 95% confidence interval (0.643–0.811). The AUROC of the G index (0.733) was higher than that of aminotransferase to platelet ratio index (APRI) (0.680) and Fibrosis index based on 4 factors (FIB-4) (0.601) in predicting significant fibrosis in children with CHB. If the values of the G index were outside the range of 0.28 to 1.16, 52% of children with CHB could avoid liver biopsy, with an overall accuracy of 75%.The G index can predict and exclude significant fibrosis in children with CHB, and it may reduce the need for liver biopsy in children with CHB.

Durability of non-nucleotide reverse transcriptase inhibitor-based first-line ART regimens after 7 years of treatment in rural Uganda: A prospective cohort study.

Most antiretroviral therapy (ART) programs in resource-limited settings have historically used non-nucleotide reverse transcriptase inhibitor (NNRTI)-based regimens with limited access to routine viral load (VL) testing. We examined the long-term success of these regimens in rural Uganda among participants with 1 measured suppressed VL.We conducted a prospective cohort study of participants who had been on NNRTI-based first-line regimens for ≥4 years and had a VL <1000 copies/mL at enrollment in Jinja, Uganda. We collected clinical and behavioral data every 6 months and measured VL again after 3 years. We quantified factors associated with virologic failure (VF) (VL ≥ 1000 copies/mL) using Wilcoxon Rank Sum, chi-square, and Fisher's Exact Tests.We enrolled 503 participants; 75.9% were female, the median age was 45 years, and the median duration of time on ART was 6.8 years (IQR = 6.0–7.6 years). Sixty-nine percent of participants were receiving nevirapine, lamivudine, and zidovudine regimens; 22.5% were receiving efavirenz, lamivudine, and zidovudine; and 8.6% were receiving other regimens. Of the 479 with complete follow-up data, 12 (2.5%) had VL ≥ 1000 copies/mL. VF was inversely associated with reporting never missing pills (41.7% of VFs vs 72.8% non-VFs, P = .034). There were differences in distribution of the previous ART regimens (P = .005), but no clear associations with specific regimens. There was no association between having a VL of 50 to 999 copies/mL at enrollment and later VF (P = .160).Incidence of VF among individuals receiving ART for nearly 7 years was very low in the subsequent 3 years. NNRTI-based regimens appear to be very durable among those with good initial adherence.

A nurse-led intervention to improve management of virological failure in public sector HIV clinics in Durban, South Africa: A pre- and post-implementation evaluation

Identification of patients on antiretroviral therapy (ART) with virological failure (VF) and the response in the public health sector remain significant challenges. We previously reported improvement in routine viral load (VL) monitoring after ART commencement through a health system-strengthening, nurse-led 'VL champion' programme as part of a multidisciplinary team in three public sector clinics in Durban, South Africa.To report on the impact of the VL champion model adapted to identify, support and co-ordinate the management of individuals with VF on first-line ART in a setting with limited electronic-based record capacity.We evaluated the VL champion model using a controlled before-after study design. A paper-based tool, the 'high VL register', was piloted under the supervision of the VL champion to improve data management, monitoring of counselling support, and enacting of clinical decisions. We abstracted chart and electronic data (TIER.net) for eligible individuals with VF in the year before and after implementation of the programme, and compared outcomes for individuals during these periods. Our primary outcome was successful completion of the VF pathway, defined as a repeat VL &lt;1 000 copies/mL or a change to second-line ART within 6 months of VF. In a secondary analysis, we assessed the completion of each step in the pathway.We identified 60 and 56 individuals in the pre-intervention and post-intervention periods, respectively, with VF who met the inclusion criteria. Sociodemographic and clinical characteristics were similar between the periods. Repeat VL testing was completed in 61.7% and 57.8% of individuals in these two groups, respectively. We found no difference in the proportion achieving our primary outcome in the pre- and post-intervention periods: 11/60 (18.3%; 95% confidence interval (CI) 9 - 28) and 15/56 (22.8%; 95% CI 15 - 38), respectively (p=0.28). In multivariable logistic regression models adjusted for potential confounding factors, individuals in the post-intervention period had a non-significant doubling of the odds of achieving the primary outcome (adjusted odds ratio 2.07; 95% CI 0.75 - 5.72). However, there was no difference in the rates of completion of each step along the first-line VF cascade of care.This enhanced intervention to improve VF in the public sector using a paper-based data management system failed to achieve significant improvements in first-line VF management over the standard of care. In addition to interventions that better address patient-centred factors that contribute to VF, we believe that there are substantial limitations to and staffing requirements involved in the ongoing utilisation of a paper-based tool. A prioritisation is needed to further expand and upgrade the electronic medical record system with capabilities for prompting staff regarding patients with missed visits and critical laboratory results demonstrating VF.

Long Turnaround Times in Viral Load Monitoring of People Living with HIV in Resource-Limited Settings.

Introduction:Routine viral load (VL) testing is fraught with challenges in resource-limited settings which lead to longer turnaround times for the return of VL results. We assessed the turnaround times for VL testing and factors associated with long turnaround (>30 days) in Marondera, Zimbabwe, between January and September 2018.Methods:This was an analytical study of routine program data. Data were extracted from electronic records and paper-based reports at two laboratories and at antiretroviral therapy (ART) facilities. The unit of analysis was the VL sample. Duration (in days) between sample collection and sample testing (pre-test turnaround time), duration between sample testing and receipt of VL result at ART the site (post-test turnaround time), and duration between sample collection and receipt of result at the ART site (overall turnaround time) were calculated. Days on which the VL testing machine was not functional, and workload (number of tests done per month) were used to assess associations. We used binomial log models to assess the factors associated with longer turnaround time.Results:A total of 3348 samples were received at the two VL testing laboratories, and 3313 were tested, of these, 1111 were analyzed for overall turnaround time. Pre-test, post-test, and overall turnaround times were 22 days (interquartile range (IQR): 11–41), 51 days (IQR: 30–89), and 67 days (IQR: 46–100), respectively. Laboratory workload (relative risk [RR]: 1.12, 95% confidence interval [CI]: 1.10–1.14) and machine break down (RR: 1.15, 95% CI: 1.14–1.17) were associated with long turnaround time.Conclusions:Routine VL turnaround time was long. Decentralizing VL testing and enhancing laboratory capacity may help shorten the turnaround time.

Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial.

Daily co-trimoxazole is recommended for African adults living with human immunodeficiency virus (HIV) irrespective of antiretroviral treatment, immune status, or disease stage. Benefits of continued prophylaxis and whether co-trimoxazole can be stopped following immune reconstitution are unknown. We conducted a randomized controlled trial at 2 sites in Malawi that enrolled adults with HIV with undetectable viral load and CD4 count of >250/mm3 and randomized them to continue daily co-trimoxazole, discontinue daily co-trimoxazole and begin weekly chloroquine, or discontinue daily co-trimoxazole. The primary endpoint was the preventive effect of co-trimoxazole prophylaxis against death or World Health Organization (WHO) HIV/AIDS stage 3-4 events, using Cox proportional hazards modeling, in an intention-to-treat population. 1499 adults were enrolled. The preventive effect of co-trimoxazole on the primary endpoint was 22% (95% CI: -14%-47%; P = .20) versus no prophylaxis and 25% (-10%-48%; P = .14) versus chloroquine. When WHO HIV/AIDS stage 2 events were added to the primary endpoint, preventive effect increased to 31% (3-51%; P = .032) and 32% (4-51%; P = .026), respectively. Co-trimoxazole and chloroquine prophylaxis effectively prevented clinical malaria episodes (3.8 and 3.0, respectively, vs 28/100 person-years; P < .001). Malawian adults with HIV who immune reconstituted on ART and continued co-trimoxazole prophylaxis experienced fewer deaths and WHO HIV/AIDS stage 3-4 events compared with prophylaxis discontinuation, although statistical significance was not achieved. Co-trimoxazole prevented a composite of death plus WHO HIV/AIDS stage 2-4 events. Given poor healthcare access and lack of routine viral load monitoring, co-trimoxazole prophylaxis should continue in adults on ART after immune reconstitution in sub-Saharan Africa. Clinical Trials Registration. NCT01650558.

Effects of National Adoption of Treat-All Guidelines on Pre-Antiretroviral Therapy (ART) CD4 Testing and Viral Load Monitoring After ART initiation: A Regression Discontinuity Analysis.

BackgroundThe World Health Organization’s Treat-All guidance recommends CD4 testing before initiating antiretroviral therapy (ART), and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART.MethodsWe used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547 837 ART-naive patients enrolling in human immunodeficiency virus (HIV) care during 2006–2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10–19 years), and children (0–9 years) in low/lower-middle-income countries (L/LMICs) and high/upper-middle-income countries (H/UMICs).ResultsTreat-All adoption led to an immediate decrease in pre-ART CD4 testing among adults in L/LMICs, from 57.0% to 48.1% (−8.9 percentage points [pp]; 95% CI: −11.0, −6.8), and a small increase in H/UMICs, from 90.1% to 91.7% (+1.6pp; 95% CI: 0.2, 3.0), with no changes among adolescents or children; decreases in pre-ART CD4 testing accelerated after Treat-All adoption in L/LMICs. In L/LMICs, VL monitoring after ART initiation was low among all patients in L/LMICs before Treat-All; while there was no immediate change at Treat-All adoption, VL monitoring trends significantly increased afterwards. VL monitoring increased among adults immediately after Treat-All adoption, from 58.2% to 61.1% (+2.9pp; 95% CI: 0.5, 5.4), with no significant changes among adolescents/children.ConclusionsWhile on-ART VL monitoring has improved in L/LMICs, Treat-All adoption has accelerated and disparately worsened suboptimal pre-ART CD4 monitoring, which may compromise care outcomes for individuals with advanced HIV.

Correlation between Cepheid GeneXpert and Abbott M2000 assays for HIV viral load measurements.

Measurement of HIV viral load (VL) is the best indicator of success of antiretroviral therapy. We investigated the correlation between results by the Cepheid GeneXpert and a standard of care VL assay (Abbott M2000). This was a prospective study of people living with HIV who attended the department for routine VL measurement with the Abbott M2000. Consenting patients agreed to provide one extra blood sample for VL measurement with the Cepheid GeneXpert assay. One hundred patients consented to participate in the study. There were 18 patients with VL ≥ 40copies/mL and 75 patients with VL < 40 copies on both assays. The two assays had 93% agreement, with a kappa of 0.79 (p < 0.001). Treating VL as a continuous variable found measurements to be significantly higher on the Cepheid GeneXpert assay than the Abbott (p = 0.002). Analysis of samples with VL ≥ 40copies/mL on either assay (n = 25) found the mean difference between the two assays to be 0.31 log10 copies/mL (95% limits of agreement: -0.63, 1.25). Whilst the measurements on the two assays are relatively highly correlated, there is a clear bias, with the Cepheid GeneXpert tending to give higher VL values.

Treatment Failure and Associated Factors among Individuals on Second Line Antiretroviral Therapy in Eastern Uganda: A Retrospective Cohort Study.

Background:ART failure is a growing public health problem and a major threat to the progress of HIV/AIDS control. In Uganda however, little is documented on treatment outcomes and their associated factors among individuals on second line ART regimen. The rapid scale-up of ART over the past has resulted in substantial reductions in morbidity and mortality. However, as millions of people must be maintained on ART for life, individuals with ART treatment failure are increasingly encountered and the numbers are expected to rise. This could be attributed to factors such as sub-standard regimens, limited access to routine viral load monitoring, treatment interruptions, suboptimal adherence, among others. The purpose of this study was to estimate 5-year cumulative treatment failure and the associated factors among individuals on second line ART regimen Eastern Uganda.Materials and methods:A retrospective analysis of 541 records of HIV positive individuals, switched to second line ART regimen from January 2012 to December 2017. Inferential statistics including the Chi square test and multivariable logistic regression analysis was applied to determine associations of treatment failure against of the selected demographic, laboratory and clinical factors was performed. Associations between treatment failure and the predictors was based on a P-value of less than 5% and confidence intervals level of 95%.Results:We reviewed 541 records of individuals on second line ART regimen, of which 350 (64.7%) were female, 226 (41.8%) were married, and 197 (36.4%) were older than 35 years. The mean age at ART initiation was 30 years (SD = 14.8), while the mean weight at ART initiation was 47 kg (SD = 18.6), (range 4-97 kg). The overall proportion of treatment failure was 23%. The cumulative mortality risk for 5 years was 12.4% and the mortality rate was 2.5 deaths per 100 individuals per year. The odds of developing treatment failure among individuals switched to ATV/r-based regimen were 44% lower as compared to individuals who were switched to LPV/r (ORadj0.56, 95% CI 0.35-0.90, P = .016). while the odds of experiencing treatment failure among individuals that used AZT at ART initiation were 43% lower as compared to individuals that used a TDF based regimen at ART initiation (ORadj0.57, 95% CI 0.33-0.98, P = .041).Conclusion:The 5 year cumulative incidence of treatment failure in a cohort of 541 individuals was 23%. The type of protease inhibitor (PI) used in second line regimen and use of AZT at ART initiation were significantly associated with treatment failure. Our study also shows that the cumulative mortality risk while on second line ART regimen was 12.4% while the mortality rate was 2.5 deaths per 100 individuals per year. Given the high level of treatment failure among individuals on second line ART regimen, yet the current ART protocols limits the use of third line ART regimens to only regional referral hospitals, the Ministry of Health should strengthen the surveillance systems for identifying individuals failing on second line ART regimen even at district hospitals and lower health facilities to facilitate timely switch to optimal regimen. The Ministry of health through the Quality Improvement Division should conduct routine onsite support supervision to sites offering ART to ensure that treatment guides and other standard of care like timely switch to appropriate regimens among others are being adhered to. Knowledge gaps identified can also be addressed through onsite Continuous Medical Educations.

Go Where the Virus Is: An HIV Micro-epidemic Control Approach to Stop HIV Transmission.

Globally, a growing majority (59%) of an estimated 38 million people living with HIV (PLHIV) know their HIV status and have achieved HIV viral suppression by adhering to antiretroviral therapy (ART).1 Individuals who achieve sustained viral suppression and undetectable levels of circulating virus through good adherence to ART live long, healthy lives and will not transmit HIV through sexual contact.2–4 The evidence that people who have achieved undetectable viral loads will not transmit HIV sexually—that “undetectable equals untransmittable” (U=U)—underscores the prevention benefits of treatment and the rationale for the global call to achieve near-universal access to ART and viral suppression among PLHIV.4–6 Conversely, HIV viral burden (viremia), generally measured by plasma viral load (HIV RNA copies/mL) assays, is the primary predictor of HIV-related disease progression, morbidity, mortality, and ongoing transmission.4,7 Essentially all HIV transmission originates from a shrinking minority of PLHIV globally (41%) who do not know their HIV infection status or have not yet achieved viral suppression,8 making support for these individuals and their risk contacts a priority for treatment and prevention efforts. Studies have identified a dose-response relationship in which each 10-fold increase in HIV plasma viral load results in an increased relative risk of HIV transmission of 2.5 to 2.9 per sexual contact.9,10 Emerging evidence suggests that even under conditions of near-universal HIV treatment coverage, high viremia and high levels of risk behavior among unserved or underserved PLHIV can sustain epidemic HIV transmission.11,12 In a recent U.S. study of HIV patients in care with a detectable viral load, only a small proportion of PLHIV reported concurrent sexual transmission risk behaviors, but most of the individuals in this group had considerably elevated viral loads, increasing the probability of transmission. The study found that viral loads were likely to be lower among those with a detectable viral load who reported always using condoms.13 High viral burden associated with acute HIV infection (AHI) is a particular concern. Acute infection is characterized by a 2–4-week period of exceptionally high viremia as HIV replicates rapidly in the body before a person’s immune system mounts a response and reduces the level of circulating virus to much lower—but typically not undetectable—levels for a period of months to years.14,15 Although only a small proportion of all PLHIV will be in this brief AHI phase at any given time, per-sex-act transmission probabilities are considerably higher during periods of acute as compared to chronic HIV infection.9,16–18 In key populations engaged in frequent behavioral risks, up to an estimated 50% of all HIV transmission occurs from individuals during AHI when viremia is very high prior to the development of an immune response including anti-HIV antibodies (Ab) that yield reactivity on third-generation Ab assays.14,17,19–24 The provision of ART during AHI and of HIV pre-exposure prophylaxis (PrEP) to the risk-network contacts of acutely infected individuals could prevent a substantial proportion of ongoing HIV transmission. An analysis in Thailand suggested that early diagnosis and treatment during AHI among men who have sex with men could avert 89% of all new infections in this population.25 Approaches that differentiate service delivery to better address the preferences and needs of unserved and underserved individuals have been identified as a priority to close outstanding gaps in access to HIV prevention and treatment.26 In implementing differentiated services, it is increasingly clear that a focus on individuals and networks with the greatest viral burdens has strategic benefit. For example, programs typically transition individuals who are receiving HIV treatment and are identified through routine viral load testing as virally suppressed to options for less frequent clinical follow-up and multimonth dispensing of their antiretroviral medications. This differentiation offers additional convenience to patients and frees up resources and provider time to focus support on virally unsuppressed individuals with greater adherence, clinical, social support, and other needs. Open in a separate window Liz Brenda Kandeyi, nurse (left), takes a client through the steps for clinical services at Kikuyu Sasa Center, Nairobi, Kenya. © 2017 Nancy Coste/FHI 360

High levels of HIV drug resistance among adults failing second-line antiretroviral therapy in Namibia.

To support optimal third-line antiretroviral therapy (ART) selection in Namibia, we investigated the prevalence of HIV drug resistance (HIVDR) at time of failure of second-line ART. A cross-sectional study was conducted between August 2016 and February 2017. HIV-infected people ≥15 years of age with confirmed virological failure while receiving ritonavir-boosted protease inhibitor (PI/r)-based second-line ART were identified at 15 high-volume ART clinics representing over >70% of the total population receiving second-line ART. HIVDR genotyping of dried blood spots obtained from these individuals was performed using standard population sequencing methods. The Stanford HIVDR algorithm was used to identify sequences with predicted resistance; genotypic susceptibility scores for potential third-line regimens were calculated. Two hundred thirty-eight individuals were enrolled; 57.6% were female. The median age and duration on PI/r-based ART at time of enrolment were 37 years and 3.46 years, respectively. 97.5% received lopinavir/ritonavir-based regimens. The prevalence of nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and PI/r resistance was 50.6%, 63.1%, and 13.1%, respectively. No significant association was observed between HIVDR prevalence and age or sex. This study demonstrates high levels of NRTI and NNRTI resistance and moderate levels of PI resistance in people receiving PI/r-based second-line ART in Namibia. Findings underscore the need for objective and inexpensive measures of adherence to identify those in need of intensive adherence counselling, routine viral load monitoring to promptly detect virological failure, and HIVDR genotyping to optimize selection of third-line drugs in Namibia.

Performance and Outcomes of Routine Viral Load Testing in People Living with HIV Newly Initiating ART in the Integrated HIV Care Program in Myanmar between January 2016 and December 2017.

Myanmar has introduced routine viral load (VL) testing for people living with HIV (PLHIV) starting first-line antiretroviral therapy (ART). The first VL test was initially scheduled at 12-months and one year later this changed to 6-months. Using routinely collected secondary data, we assessed program performance of routine VL testing at 12-months and 6-months in PLHIV starting ART in the Integrated HIV-Care Program, Myanmar, from January 2016 to December 2017. There were 7153 PLHIV scheduled for VL testing at 12-months and 1976 scheduled for VL testing at 6-months. Among those eligible for testing, the first VL test was performed in 3476 (51%) of the 12-month cohort and 952 (50%) of the 6-month cohort. In the 12-month cohort, 10% had VL > 1000 copies/mL, 79% had repeat VL tests, 42% had repeat VL > 1000 copies/mL (virologic failure) and 85% were switched to second-line ART. In the 6-month cohort, 11% had VL > 1000 copies/mL, 83% had repeat VL tests, 26% had repeat VL > 1000 copies/mL (virologic failure) and 39% were switched to second-line ART. In conclusion, half of PLHIV initiated on ART had VL testing as scheduled at 12-months or 6-months, but fewer PLHIV in the 6-month cohort were diagnosed with virologic failure and switched to second-line ART. Programmatic implications are discussed.

HIV Viral Suppression in Children in a Subnational Antiretroviral Treatment Programme in Nigeria

Background: Despite years of Paediatric Antiretroviral therapy in Nigeria, the National implementation plan for the scale up of viral load testing was only rece ntly launched. Viral load determination is the most important indicator of ART response. Material & methods: First viral load samples were collected from 663 children living with HIV between December 2017-Decemb er 2019 aged 0 - 18 years on highly active antiretroviral therapy from 4 states within Nigeria. Samples were analyzed at a Polymerase Chain Reaction laboratory of the Federal Teaching Hospital Gombe. Results: Males were 311 (46.9%) and 352 (53.1%) female. Children aged 0 - 9 years constituted 44.9% (298); 55.1% (365) were aged 10 - 18 years. This first viral load was primarily routine in 94 .2% (625); 2.9% (19) of children respectively had suspected clinical or immunological failure. ART combination was AZT/3TC/NVP in 78.1% (518/663) of CLHIV; TDF/3TC/EFV in 21.2% (141); AZT/3TC/LPV/rtv in 4 (0.6%). Prior to initiation of routine viral load testing $0.55 (366/663) CLHI V had received HAART for 1 - 5 years; 7.8% (52/663) for 6 months but 10 years. The most recent CD4 count before viral load request was ≥1000/μL in 24.7% (164) of CLHIV; 500 - 999/μL in 42.9% (285); 350 - 499 μL in 11% (73) and 1000 c/ml in 59.9% (174/311) males and 47.2% (166/352) females. Viral load was significantly lower among females (P-value 0.02). Of children aged 0 - 9 years 50.3% (150/298) had viral load > 1000 c/ml and 10 - 18 years 52.1% (190/365) (P value 0.660). Viral load was >1000 c/ml in 38.5% (20/52) of children on HAART for 6 months - 1 year and 52.2% (191/366) after receiving HAART for 1 - 5 years. 52.3% (114/218) and 55.6% (15/27) CLHIV had viral load > 1000 c/ml after receiving HAART for 6 - 10 and >10 years respectively (P value 0.29). Conclusion: About half of children on HAART have viral load > 1000 c/ml after more than 1 - 5 years on HAART. Longer duration of ART and use of AZT/3TC/NVP are associated with viral load > 1000 c/ml. Key considerations are poor adherence and/or viral drug resistance. Optimizing ART adherence and resistance monitoring remain key strategies for ART programmes.

Mixed-method estimation of population-level HIV viral suppression rate in the Western Cape, South Africa

IntroductionThere are few population-wide data on viral suppression (VS) that can be used to monitor programmatic targets in sub-Saharan Africa. We describe how routinely collected viral load (VL) data from...

Access to HIV Viral Load Testing and Antiretroviral Therapy Switch Practices: A Multicountry Prospective Cohort Study in Sub-Saharan Africa.

Poor access to HIV viral load (VL) testing prevents the timely monitoring of HIV treatment adherence and efficacy. Factors enabling clinical benefits of VL testing when added to local standards of care, can inform the development of more cost-effective routine VL scale-up plans. We compared antiretroviral therapy (ART) switch practices in 13 clinics across 6 countries, with full (N = 8), phasing-in (N = 3) or no onsite access (N = 2) to VL. The analysis used data from the Pan-African Studies to Evaluate Resistance (PASER), observing virological and drug resistance outcomes among adults receiving first- or second-line ART between 2008 and 2015. Study plasma viral load (sVL) determined at baseline, every 12 months thereafter and at the time of switch served for retrospectively validating switch decisions, categorized into "necessary," "unnecessary," and "missed." Virological failure was defined as two consecutive sVL ≥1,000 HIV-RNA copies/mL. One thousand nine hundred ninety-five of the 2,420 (82.4%) study participants had continuous virological suppression during the median 30 months of follow-up. Among the 266 virological failures (11.0%), the proportion of necessary switches were similar in clinics with full (37%), phasing-in (25%), or no access (39%) to local VL testing. Documented utilization of local VL results for the switch decision was associated with higher percentage of necessary switch (87.6% vs. 67.9%). Shorter time to necessary switch was associated with higher rates of long-term virological suppression, regardless of access to local viral load. Availability of HIV VL testing capacity does not systematically result in adequate switch practices or better virological outcomes. Systems supporting sufficient test demand execution, and actual utilization of results for patient management need strengthening.

Performance Comparison of Xpert HIV-1 Viral Load Assay and Roche Taqman and Abbott M2000 RT in Bamako, Mali.

Routine monitoring of HIV-1 Viral Load (VL) is important in patients on Antiretroviral Therapy (ART) management. Access to HIV VL remains a challenge in resource-limited settings, especially in rural areas. Universal access to VL requires more simplified and less restrictive alternatives to current conventional VL methods. The objective of this study was to evaluate the performance of the new rapid (2-hour turnaround time) Xpert HIV-1VL technique compared to Roche TaqMan and Abbott RT m2000 for HIV-1 RNA quantification in HIV- infected patients. We conducted a cross-sectional study in patients seen for routine VL monitoring between August and November 2018 in a HIV care site in Bamako. The performance of the Xpert HIV-1 VL assay was evaluated against the Roche TaqMan assay and Abbott m2000 RT assay. Performance, utility and reliability/reproducibility were verified using accuracy, sensitivity, specificity, positive and negative predictive values, Diagnostic Odds Ratio (DOR), Kappa coefficient, Pearson correlation coefficient, and Bland-Altman analysis. The Xpert assay compared well with the two current referral assays (Roche TaqMan and Abbott m2000 RT assays). Compared to Roche TaqMan assay the sensitivity was 93.10%, specificity (97.01%) and accuracy (95.20%), the correlation coefficient of Pearson (r) was 0.98 (p <0.01). Bland-Altman analysis showed a mean difference of 0.18 log10 cp/mL; (Standard Deviation) SD=0.33. Compared to the Abbott m2000 RT, the sensitivity, the specificity and the accuracy were respectively 93.44%; 92% and 92.65%. The Xpert HIV-1 VL assay showed a good correlation with a correlation coefficient of Pearson, r=0.99 (p <0.001). The overall mean difference in the HIV-1 VL values obtained by Xpert HIV-1 VL and Abbott m2000 RT assays was 0.08 log10 cp/mL; SD=0.30. Xpert HIV-1 VL showed a good performance compared to Roche TaqMan and Abbott m2000 RT. With the rapid test results (less than 2 h) and ease of testing individual specimens, the Xpert HIV-1 VL assay could be an effective alternative for HIV VL monitoring in resource-limited settings.

Trends in CD4 and viral load testing 2005 to 2018: multi-cohort study of people living with HIV in Southern Africa.

IntroductionThe World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa.MethodsWe analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm3) or failing to suppress viral replication (>1000 HIV‐RNA copies/mL) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex.ResultsAmong 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01).ConclusionsCD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub‐Saharan Africa.

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.

Getting to 90-90-90: Experiences from the MaxART Early Access to ART for All (EAAA) Trial in Eswatini.

The MaxART Consortium-led by the Eswatini Ministry of Health-implemented multiple interventions between 2012 and 2017 to achieve UNAIDS 90-90-90 targets. We summarize key findings from community outreach strategies in support of the first 90 goal, and from the Early Access to ART for All (EAAA) trial on the implementation of a "Treat All" strategy to achieve the second and third 90 goals within a government-managed public health system. The MaxART Consortium demonstrated that "Fast Track," a problem-solving approach, was effective at increasing testing coverage in the community. Compared with baseline data at 3months prior to the start of the Fast Track, there was a 273% proportional increase in HIV tests conducted among adolescent males, adolescent females, and adult men, and 722% over baseline for adolescent males. The MaxART EAAA trial further showed that implementation of the Treat All policy was associated with significant two-fold shorter time from enrollment into care to ART initiation than under the standard CD4+ cell threshold-based treatment guidelines. Finally, through the MaxART trial, Eswatini was able to identify areas for further investment, including addressing the system-side barriers to routine viral load monitoring, and designing and implementing innovative community-based approaches to reach individuals who were not more routinely accessing HIV testing and counseling services. As low- and middle-income countries adopt the Treat All approach in their national HIV care and treatment guidelines, further implementation science research is needed to understand and address the system-level barriers to achieving the benefits of Treat All for HIV-infected individuals and those at risk.