Routine Viral Load Monitoring Research Articles

High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana.

Approximately 30,000 non-citizens are living with HIV in Botswana, all of whom as of 2020 are eligible to receive free antiretroviral treatment (ART) within the country. We assessed the prevalence of HIV-1 mutational profiles [pre-treatment drug resistance (PDR) and acquired drug resistance (ADR)] among treatment-experienced (TE) and treatment-naïve (TN) non-citizens living with HIV in Botswana. A total of 152 non-citizens living with HIV were enrolled from a migrant HIV clinic at Independence Surgery, a private practice in Botswana from 2019-2021. Viral RNA isolated from plasma samples were genotyped for HIV drug resistance (HIVDR) using Sanger sequencing. Major known HIV drug resistance mutations (DRMs) in the pol region were determined using the Stanford HIV Drug Resistance Database. The proportions of HIV DRMs amongst TE and TN non-citizens were estimated with 95% confidence intervals (95% CI) and compared between the two groups. A total of 60/152 (39.5%) participants had a detectable viral load (VL) >40 copies/mL and these were included in the subsequent analyses. The median age at enrollment was 43 years (Q1, Q3: 38-48). Among individuals with VL > 40 copies/mL, 60% (36/60) were treatment-experienced with 53% (19/36) of them on Atripla. Genotyping had a 62% (37/60) success rate - 24 were TE, and 13 were TN. A total of 29 participants (78.4, 95% CI: 0.12-0.35) had major HIV DRMs, including at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) associated DRM. In TE individuals, ADR to any antiretroviral drug was 83.3% (20/24), while for PDR was 69.2% (9/13). The most frequent DRMs were nucleoside reverse transcriptase inhibitors (NRTIs) M184V (62.1%, 18/29), NNRTIs V106M (41.4%, 12/29), and K103N (34.4%, 10/29). No integrase strand transfer inhibitor-associated DRMs were reported. We report high rates of PDR and ADR in ART-experienced and ART-naïve non-citizens, respectively, in Botswana. Given the uncertainty of time of HIV acquisition and treatment adherence levels in this population, routine HIV-1C VL monitoring coupled with HIVDR genotyping is crucial for long-term ART success.

Assessment of Routine Viral Load Monitoring Services and Performance of HIV Projects. A Case of Health Facilities in Nairobi County, Kenya

Antiretroviral therapy (ART) is a cornerstone of HIV management, and viral load testing serves as the gold standard for assessing drug effectiveness and confirming treatment adherence. The objectives set by The Joint United Nations Programme on HIV/AIDS (UNAIDS) for HIV care and treatment still encounter challenges, particularly in achieving improved access to ART and associated services, including essential laboratory viral load monitoring. This study investigated gaps in routine viral load monitoring within the 95-95-95 cascade, with particular emphasis on the final 95%, which remains unattained across individual, programmatic, and population levels. The research adopted a cross-sectional survey design with a pragmatic approach, focusing on healthcare professionals providing HIV services in clinics in Nairobi. A proportional sample of 226 respondents was collected from a population of 550 to gather qualitative and quantitative data. The study yielded a 90% response rate, with 96% agreement among respondents. The findings revealed a moderately low but statistically significant positive correlation (r=0.479<0.05). The R2 value of 0.230 explained 23.3% of project performance and displayed statistical significance (p-value=0.000<0.05). Consequently, the null hypothesis was rejected, indicating a substantial relationship between routine viral load monitoring services and the performance of HIV projects. In light of these results, the study recommends the implementation of a combination of feasible strategies, tailored to differentiated care models, to address challenges in low-resource settings across various population groups. These strategies aim to enhance adherence and improve viral load suppression rates, thus promoting the objectives of HIV care and treatment.

Viral Load Pattern of HIV Positive Children and Adolescents Attending a Paediatric Infectious Diseases Clinic in Owerri, Nigeria

Background: The Viral load (VL) test measures the number of copies of HIV RNA in one milliliter of blood and is the preferred antiretroviral therapy (ART) monitoring strategy. Viral suppression is defined as patients having ≤ 1000 copies of viral RNA/ml of blood.
 Methods/Materials: This study involved the retrospective review of viral load test result of patients aged 2-19years living with HIV/AIDS and enrolled in the treatment programme of the Paediatric infectious diseases clinic of the Federal University Teaching hospital Owerri.
 Results: 117 patients met the inclusion criteria and 103 were virally suppressed giving a suppression rate of 88%. Majority of those virally suppressed were in the 15-19 age group. A logistic regression analysis to ascertain the impact of age, gender, drug regimen, and duration on ARTs on the likelihood of viral suppression showed that age, gender, and drug regimen were not significant predictors of viral suppression (p > 0.05). However, duration on ARTs was a significant predictor (p < 0.01), with patients who had been on ARTs for greater than 24 months having higher odds of viral suppression (OR = 5.42, 95% CI = 1.84-15.93) compared to those who had been on ARTs for 0-6 months.
 Conclusion: Our study provides important insights into the viral load pattern of children and adolescents living with HIV/AIDS in Owerri. It highlights the importance of early initiation of ART, adherence to ART regimen, and routine viral load monitoring to achieve and maintain viral suppression.

"They test my blood to know how much blood is in my body": the untapped potential of promoting viral load literacy to support adherence and viral suppression among adolescents living with HIV.

Achieving sustained HIV viral suppression is a key strategy to optimize the health and wellbeing of those living with HIV. Sub-optimal adherence to antiretroviral therapy (ART) in adolescents and young people living with HIV (AYPLHIV) in Southern Africa, due to a range of social and contextual factors, including poor mental health, has presented a substantial challenge to meeting targets aimed towards improving treatment outcomes and reducing transmission. With the increasing availability of viral load (VL) testing in Southern Africa, there is an opportunity to better understand the relationship between VL literacy, wellbeing and adherence among adolescents. We conducted qualitative interviews with 45 AYPLHIV aged 10-24 years in three districts (urban, peri-urban and rural) in Zimbabwe between March and August 2021. The sample was purposively selected to represent a range of experiences related to HIV status disclosure, gender, marital status and treatment experience. Separate workshops were conducted with 18 healthcare workers (HCWs) and 20 caregivers to better understand existing support mechanisms to AYPLHIV accessing ART. We used thematic analysis to examine adolescent VL literacy, treatment support networks, experiences of clinic interactions, VL testing procedures and barriers to adherence. VL literacy was consistently under-developed among participants. Comprehension of phrases commonly heard during clinic visits, such as TND (target not detected) and "high" and "low" VL, were better understood by older participants. VL testing was predominantly understood as a clinical procedure that enables HCWs to monitor treatment adherence. Absent throughout the interviews were descriptions of how viral suppression improves health and quality of life, likely fosters wellbeing and enhances self-esteem, enables participation in education and social activities, and eliminates the risk of onward transmission. It is imperative that we reconsider how routine VL monitoring is communicated to and understood by AYPLHIV. Reframing ART, including VL test results, in terms of the psychosocial benefits that viral suppression can generate is likely to be crucial to motivating AYPLHIV to maintain optimal treatment engagement and develop self-management approaches as they move into adulthood. Access to accurate information tailored to individual concerns and circumstances can support AYPLHIV to achieve wellbeing.

Assessment of HIV viral load monitoring in remote settings in Vietnam - comparing people who inject drugs to the other patients.

Increasing access to viral load (VL) monitoring is essential to fight HIV epidemics. In remote settings in Vietnam, using dried blood spot (DBS) sampling for specimen collection could improve the situation. Here, people who inject drugs (PWID) represent many newly antiretroviral therapy (ART)-initiated patients. The goals of this evaluation were to evaluate if access to VL monitoring and the rate of virological failure differed between PWID and non-PWID. Prospective cohort study of patients newly initiated on ART in remote settings in Vietnam. DBS coverage at 6, 12 and 24 months of ART was investigated. Factors associated with DBS coverage were identified through logistic regression, as were factors associated with virological failure (VL ≥1,000 copies/mL) at 6, 12 and 24 months of ART. Overall 578 patients were enrolled in the cohort, of whom 261 (45%) were PWID. DBS coverage improved from 74.7% to 82.9% between 6 and 24 months of ART (p = 0.001). PWID status was not associated with DBS coverage (p = 0.74), but DBS coverage was lower in patients who were late to clinical visits and in those in WHO stage 4 (p = 0.023 and p = 0.001, respectively). The virological failure rate decreased from 15.8% to 6.6% between 6 and 24 months of ART (p<0.001). In multivariate analysis, PWID were more at risk of failure (p = 0.001), as were patients who were late to clinical visits (p<0.001) and not fully adherent (p<0.001). Despite training and simple procedures, DBS coverage was not perfect. DBS coverage was not associated with PWID status. Close management is required for effective routine HIV VL monitoring. PWID were more at risk of failure, as were patients who were not fully adherent and patients who were late to clinical visits. Specific interventions targeting these patients are needed to improve their outcomes. Overall, efforts in coordination and communication are essential to improve global HIV care. Clinical Trial Number: NCT03249493.

HIV viral load testing and monitoring in Côte d'Ivoire: A survival analysis of viral load testing and suppression, and evaluation of adherence to national recommendations.

Routine viral load (VL) monitoring is the standard of care in Côte d'Ivoire and allows for effective treatment guidance for people living with human immunodeficiency virus (HIV) to reach viral load suppression (VLS). For VL monitoring to be effective in reducing the impact of HIV, it must be provided in accordance with national guidance. This study aimed to evaluate VL testing, VLS rates and adherence to national guidance for VL testing using data collected from three national laboratories. We collected data on VL testing between 2015-2018 from OpenELIS (OE), an open-source electronic laboratory information system. We merged data by unique patient ID for patients (0-80 years old) who received multiple VL tests to calculate time between tests. We defined VLS as HIV RNA ≤1,000 copies/mL based on Côte d'Ivoire national and WHO guidance at the time of data collection. We used the Kaplan-Meier survival estimator to estimate time between ART (antiretroviral therapy) initiation and the first VL test, time between subsequent VL tests, and to estimate the proportion of people living with HIV (PLHIV) who were virally suppressed within 12 months of ART initiation. At the first documented VL test, 79.6% of patients were virally suppressed (95% CI: 78.9-80.3). Children under 15 were the least likely to be virally suppressed (55.2%, 95% CI: 51.5-58.8). The median time from ART initiation to the first VL sample collection for testing was 7.8 months (IQR:6.2-13.4). 72.4% of patients were virally suppressed within one year of treatment initiation (95% CI:71.5-73.3). Approximately 30% of patients received a second VL test during the 4-year study period. The median time between the first and second VL tests was 24.9 months (IQR: 4.7->40). Most PLHIV received their first VL test within the recommended 12 months of ART initiation but did not receive subsequent VL monitoring tests within the recommended time frame, reducing the benefits of VL monitoring. While VLS was fairly high, children were least likely to be virally suppressed. Our findings highlight the importance of regular VL monitoring after the first VL test, especially for children.

High Drug Resistance Levels Compromise the Control of HIV Infection in Pediatric and Adult Populations in Bata, Equatorial Guinea.

A lack of HIV viral load (VL) and HIV drug resistance (HIVDR) monitoring in sub-Saharan Africa has led to an uncontrolled circulation of HIV-strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART). This study updates HIVDR data and HIV-1 variants in Equatorial Guinea (EG), providing the first data on children/adolescents in the country. From 2019-2020, 269 dried blood samples (DBS) were collected in Bata Regional Hospital (EG) from 187 adults (73 ART-naïve/114 ART-treated) and 82 children/adolescents (25 HIV-exposed-ART-naïve/57 ART-treated). HIV-1 infection was confirmed in Madrid by molecular/serological confirmatory tests and ART-failure by VL quantification. HIV-1 pol region was identified as transmitted/acquired DRM, predicted antiretroviral susceptibility (Stanfordv9.0) and HIV-1 variants (phylogeny). HIV infection was confirmed in 88.1% of the individuals and virological failure (VL &gt; 1000 HIV-1-RNA copies/mL) in 84.2/88.9/61.9% of 169 ART-treated children/adolescents/adults. Among the 167 subjects with available data, 24.6% suffered a diagnostic delay. All 125 treated had experienced nucleoside retrotranscriptase inhibitors (NRTI); 95.2% were non-NRTI (NNRTI); 22.4% had experienced integrase inhibitors (INSTI); and 16% had experienced protease inhibitors (PI). At sampling, they had received 1 (37.6%), 2 (32%), 3 (24.8%) or 4 (5.6%) different ART-regimens. Among the 43 treated children-adolescents/37 adults with sequence, 62.8/64.9% carried viruses with major-DRM. Most harbored DRM to NNRTI (68.4/66.7%), NRTI (55.3/43.3%) or NRTI+NNRTI (50/33.3%). One adult and one child carried major-DRM to PI and none carried major-DRM to INSTI. Most participants were susceptible to INI and PI. DRM was absent in 36.2% of treated patients with VL &gt; 1000 cp/mL, suggesting adherence failure. TDR prevalence in 59 ART-naïve adults was high (20.3%). One-half (53.9%) of the 141 subjects with pol sequence carried CRF02_AG. The observed high rate of ART-failure and transmitted/acquired HIVDR could compromise the 95-95-95-UNAIDS targets in EG. Routine VL and resistance monitoring implementation are mandatory for early detection of ART-failure and optimal rescue therapy selection ART regimens based on PI, and INSTI can improve HIV control in EG.

Virological failure of first-line antiretroviral therapy in children living with HIV in Indonesia and associated factors

Background The World Health Organization (WHO) recommends viral load (VL) monitoring for HIV patients on antiretroviral therapy (ART). However, availability of VL monitoring in low-income countries remains limited.&#x0D; Objective To investigate factors associated with virological failure in HIV-infected children treated without routine VL monitoring.&#x0D; Methods This cohort study was done in children living with HIV (CLHIV) registered at Cipto Mangunkusumo General Hospital from 2004 to 2021. Viral load monitoring was not routinely done. Subjects with at least one VL result after 6 months on ART were included in the study. Virological failure was defined as a VL of &gt;1,000 copies. Subjects’ data were obtained from medical records, laboratory reports, and dispensing pharmacies. Statistical analysis was done following survival analysis with hazard ratio.&#x0D; Results There were 384 children who had at least 1 VL result after ART was initiated. Median age at diagnosis was 30 months. Length of follow-up ranged from 6 to 216 months, with a mean frequency of VL monitoring of 0.7 times/person/year. Most subjects were already in clinical stages 3 and 4 (77.8%); 75% met severe immunodeficiency criteria. Virological failure was found in 45.8% of subjects after a median of 33 months on first-line ART, yielding an incidence of 3.3 per 1,000 person months. Independent associated factors were age at diagnosis of &lt;60 months (HR 1.714; 95%CI 1.13 to 2.6), severe immunodeficiency (HR 1.71; 95%CI 1.15 to 2.54), referral cases (HR 1.70; 95%CI 1.23 to 2.36), and WHO clinical staging 3 (HR 1.987; 95%CI 0.995 to 3.969) and 4 (HR 2.084; 95%CI 1.034 to 4.201). Subjects with virological failure had lower weight-for-age z-scores [median 1.92; interquartile range (IQR) -3.003 to -0.81] and height-for-age z-scores [median -2.05; IQR -2.902 to -1.04] at the time of failure.&#x0D; Conclusions In HIV-infected children treated without routine VL monitoring, age at diagnosis &lt;60 months, severe immunodeficiency, WHO clinical stage 3 and 4, and referral from other centers were associated with virological failure.

Virological failure and treatment switch after ART initiation among people living with HIV with and without routine viral load monitoring in Asia.

IntroductionViral load (VL) testing is still challenging to monitor treatment responses of antiretroviral therapy (ART) for HIV treatment programme in Asia. We assessed the association between routine VL testing and virological failure (VF) and determine factors associated with switching to second‐line regimen.MethodsAmong 21 sites from the TREAT Asia HIV Observational Database (TAHOD), people living with HIV (PLHIV) aged ≥18 years initiating ART from 2003 to 2021 were included. We calculated the average number of VL tests per patient per year between the date of ART initiation and the most recent visit. If the median average number of VL tests was ≥ 0.80 per patient per year, the site was classified as a routine VL site. A site with a median < 0.80 was classified into the non‐routine VL sites. VF was defined as VL ≥1000 copies/ml during first‐line therapy. Factors associated with VF were analysed using generalized estimating equations with Poisson distribution.ResultsOf 6277 PLHIV starting ART after 2003, 3030 (48%) were from 11 routine VL testing sites and 3247 (52%) were from 10 non‐routine VL testing sites. The median follow‐up was 9 years (IQR 5–13). The median age was 35 (30–42) years; 68% were male and 5729 (91%) started non‐nucleoside reverse‐transcriptase inhibitor‐based regimen. The median pre‐ART CD4 count in PLHIV from routine VL sites was lower compared to non‐routine VL sites (144 vs. 156 cells/mm3, p <0.001). Overall, 1021 subsequent VF at a rate of 2.15 (95% CI 2.02–2.29) per 100 person‐years (PY). VF was more frequent at non‐routine VL sites (adjusted incidence rate ratio 2.85 [95% CI 2.27–3.59]) compared to routine VL sites. Other factors associated with an increased rate of VF were age <50 years and CD4 count <350 cells/mm3. A total of 817 (13%) patients switched to second‐line regimen at a rate of 1.44 (95% CI 1.35–1.54) per 100 PY. PLHIV at routine VL monitoring sites were at higher risk of switching than those at non‐routine VL sites (adjusted sub‐hazard ratio 1.78 95% CI [1.17–2.71]).ConclusionsPLHIV from non‐routine VL sites had a higher incidence of persistent VF and a low switching regimen rate, reflecting possible under‐utilized VL testing.

HIV suppression was maintained during the COVID-19 pandemic in Malawi: a program-level cohort study

Background and ObjectivesMeasures introduced to reduce the spread of SARS-CoV-2 by the Malawi government and the national HIV care program might have compromised treatment outcomes of patients living with HIV on antiretroviral therapy (ART). We studied viral load (VL) outcomes before and during the COVID-19 epidemic in Malawi. MethodsIn this population-based cohort study, we included all routine VL measurements collected from July 2019 to December 2020 in about 650 ART clinics in Malawi. We examined differences between pandemic periods (before/during COVID-19) for i) VL monitoring, and ii) VL suppression (VLS: <1,000 copies/ml). For i) we studied the number of VL measurements over time and assessed predictors of missed measurements before and during COVID-19 in logistic regression models. For ii) we estimated the odds of VLS before and during the COVID-19 epidemic stratified by treatment regimen using generalized estimation equations adjusted for age, sex, time on ART, and type of biological sample. We imputed missing treatment regimens by population-calibrated multiple imputation. ResultsWe included 607,894 routine VL samples from 556,281 patients. VL testing declined during COVID-19 (243,729; 40%) compared to before COVID-19 (365,265; 60%), but predictors of missing tests were similar in the two periods. VLS rates increased slightly from 93% before to 94% during COVID-19. Compared to before COVID-19, the odds of VLS increased during COVID-19 for patients on protease inhibitor-based (PI) regimens (adjusted odds ratio [aOR] 1.22, 95% CI: 0.99-1.49) and for patients on integrase strand transfer inhibitor-based (INSTI) regimens (aOR 1.10, 95% CI: 1.03-1.17). There was no difference in VLS between the two periods among patients on nonnucleoside reverse transcriptase inhibitor-based (NNRTI) regimens. VLS varied by age, sex, regimen, and duration on ART, ranging from 45.1% (95% CI 40.3-50.0%) to 97.2% (95% CI 96.9-97.4%). ConclusionThere was a significant decline in VL monitoring during COVID-19, but we did not find clear evidence that the pandemic reduced VL suppression rates. Routine scheduled VL monitoring, targeted adherence support, and timely regimen switches for patients with treatment failure remain critical to improving VLS.

Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries.

As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43-81]) of 18 835 at 1 year, 10 796 (62% [41-77]) of 17 553 at 2 years, and 9177 (59% [38-91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53-80]) of 225 418 at 1 year, 145 552 (72% [48-79]) of 201 238 at 2 years, and 115 260 (65% [43-69]) of 178 458 at 3 years after ART initiation. Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents. US National Institutes of Health.

Determinants of Virological Failure Among HIV-Infected Children on First-Line Antiretroviral Therapy in West Gojjam Zone, Amhara Region, Ethiopia.

BackgroundViral load monitoring is a golden indicator for diagnosing treatment failure in patients with HIV. HIV-infected children are considered a priority group for routine viral load monitoring. Globally, the World Health Organization recommends 95% of HIV patients have viral suppression. Factors leading to virological failure are not well understood and studied. This study aimed to determine virological failure among HIV-infected children on first-line antiretroviral therapy in the West Gojjam Zone, Amhara region. Ethiopia.MethodsAn institutional-based unmatched case–control study was carried out from October 1 to October 15, 2020, among HIV-infected children on first-line antiretroviral therapy. The study included 94 cases and 276 controls, with a total sample size of 370 out of 378 HIV-infected children. A structured English version checklist was used to collect data through chart review. The data were entered using Epi-data 4.2 and exported into SPSS version 20 for analysis. Descriptive statistics were conducted to summarize the sample characteristics. Bivariate and multivariate analyses were used to describe each explanatory variable’s association with the outcome variable. A bivariate analysis with a p-value < 0.25 was selected for multivariate analysis. Adjusted odds ratio with 95% confidence intervals was conducted, and p-value < 0.05 was considered statistically significant.ResultsNon-disclosure (AOR = 4.26; 95% CI: 2.09, 8.70), baseline viral load >1000 copies/mL (AOR = 10.82; 95% CI: 5.4, 21.67), recent poor adherence (AOR, 6.05, 95% CI, 1.70, 21.55) and missed clinical appointments (AOR = 8.03; 95% CI: 3.88, 16.65) were factors independently associated with virological failure.ConclusionDisclosure of HIV status of patients early, according to their age and adherence to counseling, should be emphasized. Efforts should be strengthened to trace back for missed clinical appointments and strictly follow-up with antiretroviral (ARV) medication for a baseline viral load >1000 copies/mL that helps to boost immunity and suppress viral replication.

The Suboptimal Pediatric HIV Viral Load Cascade: Multidistrict Cohort Study Among Children Taking Antiretroviral Therapy in Lesotho, Southern Africa.

Children living with HIV and taking antiretroviral therapy (ART) are a priority group for routine viral load (VL) monitoring. As per Lesotho guidelines, a VL ≥1000 copies/mL ("unsuppressed") should trigger adherence counseling and a follow-up VL; 2 consecutive unsuppressed VLs ("virologic failure") qualify for switching to second-line ART, with some exceptions. Here, we describe the pediatric VL cascade in Lesotho. In a prospective open cohort study comprising routine VL results from 22 clinics in Lesotho, we assessed outcomes along the VL cascade for children who had at least 1 VL test from January 2016 through June 2020. Data were censored on February 10, 2021. In total, 1215 children received 5443 VL tests. The median age was 10 years (interquartile range 7-13) and 627/1215 (52%) were female; 362/1215 (30%) had at least 1 unsuppressed VL. A follow-up VL was available for 325/362 (90%), although only for 159/362 (44%) within 6 months of the first unsuppressed VL. Of those with a follow-up VL, 172/329 (53%) had virologic failure and 123/329 (37%) qualified for switching to second-line ART. Of these, 55/123 (45%) were ever switched, although only 9/123 (7%) were switched within 12 weeks of the follow-up VL. Delays were more pronounced in rural facilities. Overall, 100/362 (28%) children with an unsuppressed VL received a timely follow-up VL and, if required, a timely regimen switch. Despite access to VL monitoring, clinical management was suboptimal. HIV programs should prioritize timely clinical action to maximize the benefits of VL monitoring.

Experiences With Safer Conception Services for HIV-Serodiscordant Couples at a Referral Hospital in Nairobi, Kenya.

Human immunodeficiency virus-serodiscordant couples are an important source of new HIV infections in Africa. When trying to conceive, uninfected partners may be at high risk of infection if the infected partner is not virally suppressed. Multiple strategies targeting safer conception exist, but these services are limited. However, when services are available and used, serodiscordant couples can be protected from HIV transmission, and safe to have children if desired. To successfully introduce, integrate, promote, and optimize the service delivery of safer conception with HIV care, it is crucial to understand how HIV-serodiscordant couples perceive and experience these services. Further, viral load monitoring can be critical to safer conception, but there is limited literature on how it informs the decision of the partners about conception. This qualitative study describes the knowledge, perceptions, and experiences of both safer conception services and viral load monitoring among 26 HIV-serodiscordant couples seeking safer conception care at a referral hospital in Nairobi, Kenya. In-depth interviews of HIV-serodiscordant couples were conducted from April to July 2017, and transcripts were analyzed to identify the themes central to the experience of safer conception services of couples and viral load monitoring. Serodiscordant couples reported success in using some of the safer conception methods and had positive experiences with healthcare providers. However, despite using the services, some were concerned about HIV transmission to the seronegative partner and baby, while others faced challenges when using pre-exposure prophylaxis (PrEP) and vaginal insemination. Overall, their motivation to have children overcame their concern about HIV transmission, and they welcomed discussions on risk reduction. Moreover, supportive clinic staff was identified as key to facilitating trust in safer conception methods. Furthermore, viral load monitoring was identified as integral to safer conception methods, an emerging theme that requires further evaluation, especially where routine viral load monitoring is not performed. In conclusion, healthcare providers offering safer conception services should build trust with couples, and recognize the need for continual couple counseling to encourage the adoption of safer conception services.

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.

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.

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.

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 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.