Effectiveness of intensive adherence counselling in achieving an undetectable viral load among people on antiretroviral therapy with low-level viraemia in Uganda.

INTRODUCTION: Uganda was using a threshold of 1000 copies/mL to determine viral non-suppression for antiretroviral therapy monitoring among people living with HIV, prior to this study. It was not clear whether people living with HIV with low-level viraemia (LLV, ≥50 to <1000 copies/mL) would benefit from intensive adherence counselling (IAC). The purpose of this study was to determine the effectiveness of IAC among people living with HIV, receiving antiretroviral therapy, and with LLV in Uganda, to guide key policy decisions in HIV care, including the review of the viral load (VL) testing algorithm. METHODS: This cluster-randomized clinical trial comprised adults from eight HIV clinics who were living with HIV, receiving ART, and had recent VL results indicating LLV (tested from July 2022 to October 2022). Participants in the intervention arm clinics received three once-monthly sessions of IAC, and those in the comparison non-intervention arm clinics received the standard of care. At the end of the study, all participants were re-tested for VL to determine the proportions of those who then had an undetectable VL (<50 copies/mL). We assessed the statistical association between cross-tabulated variables using Fisher's exact test and then modified Poisson regression. RESULTS: A total of 136 participants were enrolled into the study at eight HIV clinics. All 68 participants in the intervention arm completed all IAC sessions. Only one participant in the non-intervention arm was lost to follow-up. The average follow-up time was 3.7 months (standard deviation [SD] 0.2) and 3.5 months (SD 0.1) in the intervention and non-intervention arms, respectively. In total, 59 (43.7%) of 135 people living with HIV achieved an undetectable VL during the study follow-up period. The effect of IAC on attaining an undetectable VL among people with LLV was nearly twice as high in the intervention arm (57.4%) than in the non-intervention arm (29.9%): adjusted risk ratio 1.9 (95% confidence interval 1.0-3.5), p = 0.037. CONCLUSION: IAC doubled the likelihood of an undetectable VL among people living with HIV with LLV. Therefore, IAC has been instituted as an intervention to manage people living with HIV with LLV in Uganda, and this should also be adopted in other Sub-Saharan African countries with similar settings. GOV IDENTIFIER: NCT05514418.

Trends in sickle cell trait and disease screening in the Republic of Uganda, 2014-2019.

OBJECTIVE: Sickle cell disease is an important public health issue that is increasingly recognised as a substantial contributor to morbidity and early childhood mortality in sub-Saharan Africa. We aimed to provide information from large-scale, long-term sickle cell screening efforts in Africa. METHODS: We used nationally representative data from the centralised public health laboratory database in Uganda to examine epidemiological trends in sickle cell screening over a five-year period, comparing age and geographic adjustments to prevalence among different testing cohorts of children aged 0-24 months, and calculating screening coverage within high-burden districts. RESULTS: A total of 324 356 children aged 0-24 months were screened for sickle cell trait and disease from February 2014 to March 2019. A high national burden of sickle cell disease (0.9%) was confirmed among a cohort of samples co-tested with HIV. In the cohort of samples referred specifically for sickle cell testing, the overall prevalence of sickle cell disease was 9.7% and particularly elevated in high-burden districts where focused screening occurred. The majority of children were screened before age 4 months, but the sickle-specific cohort had a larger proportion of affected children tested between age 5-9 months, coincident with onset of disease signs and symptoms. Successful screening coverage of sickle cell disease births was achieved in several high-burden districts. CONCLUSIONS: Examination and analysis of national sickle cell screening trends in Uganda documents the successes of focused screening strategies as an important step towards universal screening. With this evidence and increased healthcare provider knowledge, Uganda can optimise sickle cell diagnosis and management across the country.

OBJECTIF: La drépanocytose est un problème important de santé publique, de plus en plus reconnu comme un contributeur important à la morbidité et à la mortalité infantile en Afrique subsaharienne. Notre objectif était de fournir des informations sur les efforts de dépistage de la drépanocytose à grande échelle et à long terme en Afrique. MÉTHODES: Nous avons utilisé des données représentatives nationales de la base de données centralisée des laboratoires de santé publique en Ouganda pour examiner les tendances épidémiologiques dans le dépistage de la drépanocytose sur une période de cinq ans, en comparant l'âge et les ajustements géographiques à la prévalence dans différentes cohortes de tests d'enfants âgés de 0 à 24 mois, et en estimant la couverture du dépistage dans les districts à forte charge. RÉSULTATS: Un total de 324.356 enfants âgés de 0 à 24 mois ont été dépistés pour le trait drépanocytaire et la maladie de février 2014 à mars 2019. Une charge nationale élevée de la drépanocytose (0,9%) a été confirmée dans une cohorte d'échantillons co-testés pour le VIH. Dans la cohorte d'échantillons référés spécifiquement pour le dépistage de la drépanocytose, la prévalence globale de la drépanocytose était de 9,7% et particulièrement élevée dans les districts à forte charge où un dépistage ciblé avait eu lieu. La majorité des enfants ont été dépistés avant l'âge de 4 mois, mais la cohorte spécifique pour la drépanocytose avait une plus grande proportion d'enfants affectés testés entre l'âge de 5 à 9 mois, coïncidant avec l'apparition des signes et symptômes de la maladie. Une bonne couverture de dépistage des naissances drépanocytaires a été obtenue dans plusieurs districts à forte charge. CONCLUSIONS: L'examen et l'analyse des tendances nationales du dépistage de la drépanocytose en Ouganda documentent les succès des stratégies de dépistage ciblé comme une étape importante vers le dépistage universel. Grâce à ces données et à une meilleure connaissance des prestataires de soins de santé, l'Ouganda peut optimiser le diagnostic et la prise en charge de la drépanocytose dans tout le pays.

Implementation and operational feasibility of SAMBA I HIV-1 semi-quantitative viral load testing at the point-of-care in rural settings in Malawi and Uganda.

OBJECTIVE: We monitored a large-scale implementation of the Simple Amplification-Based Assay semi-quantitative viral load test for HIV-1 version I (SAMBA I Viral Load = SAMBA I VL) within Médecins Sans Frontières' HIV programmes in Malawi and Uganda, to assess its performance and operational feasibility. METHODS: Descriptive analysis of routine programme data between August 2013 and December 2016. The dataset included samples collected for VL monitoring and tested using SAMBA I VL in five HIV clinics in Malawi (four peripheral health centres and one district hospital), and one HIV clinic in a regional referral hospital in Uganda. SAMBA I VL was used for VL testing in patients who had been receiving ART for between 6 months and ten years, to determine whether plasma VL was above or below 1000 copies/mL of HIV-1, reflecting ART failure or efficacy. Randomly selected samples were quantified with commercial VL assays. SAMBA I instruments and test performance, site throughput, and delays in communicating results to clinicians and patients were monitored. RESULTS: Between August 2013 and December 2016 a total of 60 889 patient samples were analysed with SAMBA I VL. Overall, 0.23% of initial SAMBA I VL results were invalid; this was reduced to 0.04% after repeating the test once. Global test failure, including instrument failure, was 1.34%. Concordance with reference quantitative testing of VL was 2620/2727, 96.0% (1338/1382, 96.8% in Malawi; 1282/1345, 95.3% in Uganda). For Chiradzulu peripheral health centres and Arua Hospital HIV clinic, where testing was performed on-site, same-day results were communicated to clinicians for between 91% and 97% of samples. Same-day clinical review was obtained for 84.7% across the whole set of samples tested. CONCLUSIONS: SAMBA I VL testing is feasible for monitoring cohorts of 1000 to 5000 ART-experienced patients. Same-day results can be used to inform rapid clinical decision-making at rural and remote health facilities, potentially reducing time available for development of resistance and conceivably helping to reduce morbidity and mortality.

OBJECTIF: Nous avons suivi une mise en œuvre à grande échelle du test de la charge virale semi-quantitative du VIH -1 basé sur de Test de Simple Amplification version I (SAMBA I Viral Load = SAMBA I VL) au sein des programmes VIH de Médecins Sans Frontières au Malawi et en Ouganda, afin d'évaluer sa performance et sa faisabilité opérationnelle. MÉTHODES: Analyse descriptive des données du programme de routine entre août 2013 et décembre 2016. L'ensemble des données comprenait des échantillons collectés pour le suivi de la CV et testés à l'aide de SAMBA I VL dans cinq cliniques VIH au Malawi (quatre centres de santé périphériques et un hôpital de district), et une clinique VIH dans un hôpital régional de référence en Ouganda. SAMBA I VL a été utilisé pour le test de la CV chez les patients qui recevaient l'ART depuis 6 mois à dix ans, afin de déterminer si la CV plasmatique était supérieure ou inférieure à 1000 copies/ml de VIH-1, reflétant l'échec ou l'efficacité de l'ART. Des échantillons sélectionnés aléatoirement ont été quantifiés avec des tests de CV commerciaux. Les instruments de SAMBA I et les performances des tests, le débit du site et les délais dans la communication des résultats aux cliniciens et aux patients ont été suivis. RÉSULTATS: Entre août 2013 et décembre 2016, un total de 60.889 échantillons de patients ont été analysés avec SAMBA I VL. Dans l'ensemble, 0,23% des résultats initiaux de SAMBA I VL étaient invalides; ceux-ci ont été été réduits à 0,04% après avoir répété le test une fois. L'échec global du test, y compris l'échec de l'instrument, était de 1,34%. La concordance avec les tests quantitatifs de référence de la CV était de 2620/2727; 96,0% (1338/1382; 96,8% au Malawi; 1282/1345; 95,3% en Ouganda). Pour les centres de santé périphériques de Chiradzulu et la clinique VIH de l'hôpital d'Arua, où les tests ont été effectués sur place, les résultats ont été communiqués le jour même aux cliniciens pour entre 91% et 97% des échantillons. Un examen clinique le jour même a été obtenu pour 84,7% de l'ensemble des échantillons testés. CONCLUSIONS: Le test SAMBA I VL est réalisable pour le suivi de cohortes de 1.000 à 5.000 patients déjà sous ART. Les résultats le jour même peuvent être utilisés pour éclairer la prise de décision clinique rapide dans les établissements de santé ruraux et éloignés, réduisant potentiellement le temps disponible pour le développement de la résistance et contribuant éventuellement à réduire la morbidité et la mortalité.

HIV Viral Load Monitoring Among Patients Receiving Antiretroviral Therapy - Eight Sub-Saharan Africa Countries, 2013-2018.

One component of the Joint United Nations Programme on HIV/AIDS (UNAIDS) goal to end the HIV/AIDS epidemic by 2030, is that 95% of all persons receiving antiretroviral therapy (ART) achieve viral suppression.† Thus, testing all HIV-positive persons for viral load (number of copies of viral RNA per mL) is a global health priority (1). CDC and other U.S. government agencies, as part of the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), together with other stakeholders, have provided technical assistance and supported the cost for multiple countries in sub-Saharan Africa to expand viral load testing as the preferred monitoring strategy for clinical response to ART. The individual and population-level benefits of ART are well understood (2). Persons receiving ART who achieve and sustain an undetectable viral load do not transmit HIV to their sex partners, thereby disrupting onward transmission (2,3). Viral load testing is a cost-effective and sustainable programmatic approach for monitoring treatment success, allowing reduced frequency of health care visits for patients who are virally suppressed (4). Viral load monitoring enables early and accurate detection of treatment failure before immunologic decline. This report describes progress on the scale-up of viral load testing in eight sub-Saharan African countries from 2013 to 2018 and examines the trajectory of improvement with viral load testing scale-up that has paralleled government commitments, sustained technical assistance, and financial resources from international donors. Viral load testing in low- and middle-income countries enables monitoring of viral load suppression at the individual and population level, which is necessary to achieve global epidemic control. Although there has been substantial achievement in improving viral load coverage for all patients receiving ART, continued engagement is needed to reach global targets.

Next generation sequencing based in-house HIV genotyping method: validation report.

BACKGROUND: HIV genotyping has had a significant impact on the care and treatment of HIV/AIDS. At a clinical level, the test guides physicians on the choice of treatment regimens. At the surveillance level, it informs policy on consolidated treatment guidelines and microbial resistance control strategies. Until recently, the conventional test has utilized the Sanger sequencing (SS) method. Unlike Next Generation Sequencing (NGS), SS is limited by low data throughput and the inability of detecting low abundant drug-resistant variants. NGS can improve sensitivity and quantitatively identify low-abundance variants; in addition, it has the potential to improve efficiency as well as lowering costs when samples are batched. Despite the NGS benefits, its utilization in clinical drug resistance profiling is faced with mixed reactions. These are largely based on a lack of a consensus regarding the quality control strategy. Nonetheless, transitional views suggest validating the method against the gold-standard SS. Therefore, we present a validation report of an NGS-based in-house HIV genotyping method against the SS method in Uganda. RESULTS: Since there were no established proficiency test panels for NGS-based HIV genotyping, 15 clinical plasma samples for routine care were utilized. The use of clinical samples allowed for accuracy and precision studies. The workflow involved four main steps; viral RNA extraction, targeted amplicon generation, amplicon sequencing and data analysis. Accuracy of 98% with an average percentage error of 3% was reported for the NGS based assay against the SS platform demonstrating similar performance. The coefficient of variation (CV) findings for both the inter-run and inter-personnel precision showed no variability (CV ≤ 0%) at the relative abundance of ≥ 20%. For both inter-run and inter-personnel, a variation that affected the precision was observed at 1% frequency. Overall, for all the frequencies, CV registered a small range of (0-2%). CONCLUSION: The NGS-based in-house HIV genotyping method fulfilled the minimum requirements that support its utilization for drug resistance profiling in a clinical setting of a low-income country. For more inclusive quality control studies, well-characterized wet panels need to be established.

Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy-Experienced Ugandans With Virologic Failure.

BACKGROUND: Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus-positive persons with CD4 count <100 cells/µL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. METHODS: We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017-January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. RESULTS: Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10-84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8-19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL. CONCLUSIONS: In addition to the CD4 threshold of <100 cells/µL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.

Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers.

BACKGROUND: The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV-exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. METHODS: A 3-year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high-burden districts, (2) document the prevalence among HIV-exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co-inheritance of known genetic modifiers of sickle cell disease. RESULTS: A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid-Northern districts, in both HIV-exposed and nonexposed children. Based on crude birth-rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40-0.64, P < .0001). Alpha-thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. CONCLUSIONS: High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district-level comprehensive care programs.

A cholera outbreak caused by drinking contaminated river water, Bulambuli District, Eastern Uganda, March 2016.

BACKGROUND: A cholera outbreak started on 29 February in Bwikhonge Sub-county, Bulambuli District in Eastern Uganda. Local public health authorities implemented initial control measures. However, in late March, cases sharply increased in Bwikhonge Sub-county. We investigated the outbreak to determine its scope and mode of transmission, and to inform control measures. METHODS: We defined a suspected case as sudden onset of watery diarrhea from 1 March 2016 onwards in a resident of Bulambuli District. A confirmed case was a suspected case with positive stool culture for V. cholerae. We conducted descriptive epidemiologic analysis of the cases to inform the hypothesis on mode of transmission. To test the hypothesis, we conducted a case-control study involving 100 suspected case-patients and 100 asymptomatic controls, individually-matched by residence village and age. We collected seven water samples for laboratory testing. RESULTS: We identified 108 suspected cases (attack rate: 1.3%, 108/8404), including 7 confirmed cases. The case-control study revealed that 78% (78/100) of case-patients compared with 51% (51/100) of control-persons usually collected drinking water from the nearby Cheptui River (ORMH = 7.8, 95% CI = 2.7-22); conversely, 35% (35/100) of case-patients compared with 54% (54/100) of control-persons usually collected drinking water from borehole pumps (ORMH = 0.31, 95% CI = 0.13-0.65). The index case in Bwikhonge Sub-county had onset on 29 February but the outbreak had been on-going in the neighbouring sub-counties in the previous 3 months. V. cholera was isolated in 2 of the 7 river water samples collected from different locations. CONCLUSIONS: We concluded that this cholera outbreak was caused by drinking contaminated water from Cheptui River. We recommended boiling and/or treating drinking water, improved sanitation, distribution of chlorine tablets to the affected villages, and as a long-term solution, construction of more borehole pumps. After implementing preventive measures, the number of cases declined and completely stopped after 6th April.

Retention outcomes and drivers of loss among HIV-exposed and infected infants in Uganda: a retrospective cohort study.

BACKGROUND: Uganda's HIV Early Infant Diagnosis (EID) program rapidly scaled up testing of HIV-exposed infants (HEI) in its early years. However, little was known about retention outcomes of HEI after testing. Provision of transport refunds to HEI caregivers was piloted at 3 hospitals to improve retention. This study was conducted to quantify retention outcomes of tested HEI, identify factors driving loss-to-follow-up, and assess the effect of transport refunds on HEI retention. METHODS: This mixed-methods study included 7 health facilities- retrospective cohort review at 3 hospitals and qualitative assessment at all facilities. The cohort comprised all HEI tested from September-2007 to February-2009. Retention data was collected manually at each hospital. Qualitative methods included health worker interviews and structured clinic observation. Qualitative data was synthesized, analyzed and triangulated to identify factors driving HEI loss-to-follow-up. RESULTS: The cohort included 1268 HEI, with 244 testing HIV-positive. Only 57% (718/1268) of tested HEI received results. The transport refund pilot increased the percent of HEI caregivers receiving test results from 54% (n = 763) to 58% (n = 505) (p = .08). HEI were tested at late ages (Mean = 7.0 months, n = 1268). Many HEI weren't tested at all: at 1 hospital, only 18% (67/367) of HIV+ pregnant women brought their HEI for testing after birth. Among HIV+ infants, only 40% (98/244) received results and enrolled at an ART Clinic. Of enrolled HIV+ infants, only 43% (57/98) were still active in chronic care. 36% (27/75) of eligible HIV+ infants started ART. Our analysis identified 6 categories of factors driving HEI loss-to-follow-up: fragmentation of EID services across several clinics, with most poorly equipped for HEI care/follow-up; poor referral mechanisms and data management systems; inconsistent clinical care; substandard counseling; poor health worker knowledge of EID; long sample-result turnaround times. DISCUSSION: The poor outcomes for HEI and HIV+ infants have highlighted an urgent need to improve retention and linkage to care. To address the identified gaps, Uganda's Ministry of Health and the Clinton Health Access Initiative developed a new implementation model, shifting EID from a lab-based diagnostic service to an integrated clinic-based chronic care model. This model was piloted at 21 facilities. An evaluation is needed.

Factors Associated with Virological Non-suppression among HIV-Positive Patients on Antiretroviral Therapy in Uganda, August 2014-July 2015.

BACKGROUND: Despite the growing number of people on antiretroviral therapy (ART), there is limited information about virological non-suppression and its determinants among HIV-positive (HIV+) individuals enrolled in HIV care in many resource-limited settings. We estimated the proportion of virologically non-suppressed patients, and identified the factors associated with virological non-suppression. METHODS: We conducted a descriptive cross-sectional study using routinely collected program data from viral load (VL) samples collected across the country for testing at the Central Public Health Laboratories (CPHL) in Uganda. Data were generated between August 2014 and July 2015. We extracted data on socio-demographic, clinical and VL testing results. We defined virological non-suppression as having ≥1000 copies of viral RNA/ml of blood for plasma or ≥5000 copies of viral RNA/ml of blood for dry blood spots. We used logistic regression to identify factors associated with virological non-suppression. RESULTS: The study was composed of 100,678 patients; of these, 94,766(94%) were for routine monitoring, 3492(4%) were suspected treatment failures while 1436(1%) were repeat testers after suspected failure. The overall proportion of non-suppression was 11%. Patients on routine monitoring registered the lowest (10%) proportion of non-suppressed patients. Virological non-suppression was higher among suspected treatment failures (29%) and repeat testers after suspected failure (50%). Repeat testers after suspected failure were six times more likely to have virological non-suppression (ORadj = 6.3, 95%CI = 5.5-7.2) when compared with suspected treatment failures (ORadj = 3.3, 95%CI = 3.0-3.6). The odds of virological non-suppression decreased with increasing age, with children aged 0-4 years (ORadj = 5.3, 95%CI = 4.6-6.1) and young adolescents (ORadj = 4.1, 95%CI = 3.7-4.6) registering the highest odds. Poor adherence (ORadj = 3.4, 95%CI = 2.9-3.9) and having active TB (ORadj = 1.9, 95%CI = 1.6-2.4) increased the odds of virological non-suppression. However, being on second/third line regimens (ORadj = 0.86, 95%CI = 0.78-0.95) protected patients against virological non-suppression. CONCLUSION: Young age, poor adherence and having active TB increased the odds of virological non-suppression while second/third line ART regimens were protective against non-suppression. We recommend close follow up and intensified targeted adherence support for repeat testers after suspected failure, children and adolescents.

Early Diagnosis of HIV Infection in Infants - One Caribbean and Six Sub-Saharan African Countries, 2011-2015.

Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged <15 years were estimated to be living with HIV (including 170,000 infants born in 2015), with the vast majority living in sub-Saharan Africa (1). In 2014, 150,000 children died from HIV-related causes worldwide (2). Access to timely HIV diagnosis and treatment for HIV-infected infants reduces HIV-associated mortality, which is approximately 50% by age 2 years without treatment (3). Since 2011, the annual number of HIV-infected children has declined by 50%. Despite this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test for HIV (2), and in 2015, only 51% of children living with HIV received antiretroviral therapy (1). Access to services for early infant diagnosis of HIV (which includes access to testing for HIV-exposed infants and clinical diagnosis of HIV-infected infants) is critical for reducing HIV-associated mortality in children aged <15 years. Using data collected from seven countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the provision of HIV testing services for early infant diagnosis was assessed. During 2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as recommended by the World Health Organization (WHO) increased in all seven countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi, South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV positivity among those tested declined in all seven countries, with three countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda) reporting >50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection.

Progress with Scale-Up of HIV Viral Load Monitoring - Seven Sub-Saharan African Countries, January 2015-June 2016.

The World Health Organization (WHO) recommends viral load testing as the preferred method for monitoring the clinical response of patients with human immunodeficiency virus (HIV) infection to antiretroviral therapy (ART) (1). Viral load monitoring of patients on ART helps ensure early diagnosis and confirmation of ART failure and enables clinicians to take an appropriate course of action for patient management. When viral suppression is achieved and maintained, HIV transmission is substantially decreased, as is HIV-associated morbidity and mortality (2). CDC and other U.S. government agencies and international partners are supporting multiple countries in sub-Saharan Africa to provide viral load testing of persons with HIV who are on ART. This report examines current capacity for viral load testing based on equipment provided by manufacturers and progress with viral load monitoring of patients on ART in seven sub-Saharan countries (Côte d'Ivoire, Kenya, Malawi, Namibia, South Africa, Tanzania, and Uganda) during January 2015-June 2016. By June 2016, based on the target numbers for viral load testing set by each country, adequate equipment capacity existed in all but one country. During 2015, two countries tested >85% of patients on ART (Namibia [91%] and South Africa [87%]); four countries tested <25% of patients on ART. In 2015, viral suppression was >80% among those patients who received a viral load test in all countries except Côte d'Ivoire. Sustained country commitment and a coordinated global effort is needed to reach the goal for viral load monitoring of all persons with HIV on ART.

Scale-up of HIV Viral Load Monitoring--Seven Sub-Saharan African Countries.

To achieve global targets for universal treatment set forth by the Joint United Nations Programme on human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (UNAIDS), viral load monitoring for HIV-infected persons receiving antiretroviral therapy (ART) must become the standard of care in low- and middle-income countries (LMIC) (1). CDC and other U.S. government agencies, as part of the President's Emergency Plan for AIDS Relief, are supporting multiple countries in sub-Saharan Africa to change from the use of CD4 cell counts for monitoring of clinical response to ART to the use of viral load monitoring, which is the standard of care in developed countries. Viral load monitoring is the preferred method for immunologic monitoring because it enables earlier and more accurate detection of treatment failure before immunologic decline. This report highlights the initial successes and challenges of viral load monitoring in seven countries that have chosen to scale up viral load testing as a national monitoring strategy for patients on ART in response to World Health Organization (WHO) recommendations. Countries initiating viral load scale-up in 2014 observed increases in coverage after scale-up, and countries initiating in 2015 are anticipating similar trends. However, in six of the seven countries, viral load testing coverage in 2015 remained below target levels. Inefficient specimen transport, need for training, delays in procurement and distribution, and limited financial resources to support scale-up hindered progress. Country commitment and effective partnerships are essential to address the financial, operational, technical, and policy challenges of the rising demand for viral load monitoring.

The association between low-level viraemia and subsequent viral non-suppression among people living with HIV/AIDS on antiretroviral therapy in Uganda.

BACKGROUND: Uganda's efforts to end the HIV epidemic by 2030 are threatened by the increasing number of PLHIV with low-level viraemia (LLV). We conducted a study to determine the prevalence of LLV and the association between LLV and subsequent viral non-suppression from 2016 to 2020 among PLHIV on ART in Uganda. METHOD: This was a retrospective cohort study, using the national viral load (VL) program data from 2016 to 2020. LLV was defined as a VL result of at least 50 copies/ml, but less than 1,000 copies/ml. Multivariable logistic regression was used to determine the factors associated with LLV, and cox proportional hazards regression model was used to determine the association between LLV and viral non-suppression. RESULTS: A cohort of 17,783 PLHIV, of which 1,466 PLHIV (8.2%) had LLV and 16,317 (91.8%) had a non-detectable VL was retrospectively followed from 2016 to 2020. There were increasing numbers of PLHIV with LLV from 2.0% in 2016 to 8.6% in 2020; and LLV was associated with male sex, second line ART regimen and being of lower age. 32.5% of the PLHIV with LLV (476 out of 1,466 PLHIV) became non-suppressed, as compared to 7.7% of the PLHIV (1,254 out of 16,317 PLHIV) with a non-detectable viral load who became non-suppressed during the follow-up period. PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL (adjusted hazard ratio was 4.1, 95% CI: 3.7 to 4.7, p < 0.001). CONCLUSION: Our study indicated that PLHIV with LLV increased from 2.0% in 2016 to 8.6% in 2020, and PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL. Hence the need to review the VL testing algorithm and also manage LLV in Uganda.

Hopes, joys and fears: Meaning and perceptions of viral load testing and low-level viraemia among people on antiretroviral therapy in Uganda: A qualitative study.

Uganda applies the World Health Organization threshold of 1,000 copies/ml to determine HIV viral non-suppression. While there is an emerging concern of low-level viraemia (≥50 to <1,000 copies/ml), there is limited understanding of how people on antiretroviral therapy perceive viral load testing and low-level viremia in resource-limited settings. This qualitative study used the health belief model to explore the meaning that people living with HIV attach to viral load testing and low-level viraemia in Uganda. We used stratified purposive sampling to select people on antiretroviral therapy from eight high volume health facilities from the Central, Eastern, Northern and Western regions of Uganda. We used an interview guide, based on the health belief model, to conduct 32 in-depth interviews, which were audio-recorded and transcribed verbatim. Thematic analysis technique was used to analyze the data with the help of ATLAS.ti 6. The descriptions of viral load testing used by the participants nearly matched the medical meaning, and many people living with HIV understood what viral load testing was. Perceived benefits for viral load testing were the ability to show; the amount of HIV in the body, how the people living with HIV take their drugs, whether the drugs are working, and also guide the next treatments steps for the patients. Participants reported HIV stigma, lack of transport, lack of awareness for viral load testing, delayed and missing viral load results and few health workers as the main barriers to viral load testing. On the contrary, most participants did not know what low-level viraemia meant, while several perceived it as having a reduced viral load that is suppressed. Many people living with HIV are unaware about low-level viraemia, and hence do not understand its associated risks. Likewise, some people living with HIV are still not aware about viral load testing. Lack of transport, HIV stigma and delayed viral load results are major barriers to viral load testing. Hence, there is an imminent need to institute more strategies to create awareness about both low-level viraemia and viral load testing, manage HIV related stigma, and improve turnaround time for viral load results.

The plasma separation card as a novel solution for enhancing central laboratory capability for HIV-1 viral load monitoring in limited-access settings.

Measurement of HIV-1 viral load (VL) is essential for monitoring antiretroviral treatment (ART) efficacy. The preferred specimen type for VL is plasma, but in remote settings where collection and preservation of plasma many not be possible, dried blood spots (DBS) are often used instead. A new specimen collection matrix, the cobas plasma separation card (PSC, Roche Diagnostics Solutions), enables specimen preparation from a finger prick or venous blood, using a multi-layer absorption and filtration design that results in a specimen similar to dried plasma. We sought to confirm the correlation between VL results obtained using PSC prepared from venous blood to those from plasma or DBS, as well as PSC prepared with capillary blood from a finger prick. PSC, DBS and plasma were prepared with blood from HIV-1 infected persons attending a primary care clinic in Kampala, Uganda. VL in PSC and plasma was measured using cobas HIV-1 (Roche Diagnostics), while VL in DBS was measured with RealTime HIV-1 (Abbott Diagnostics). The correlation between VL from plasma and PSC made from capillary or venous blood was high (regression coefficient of determination r2 between 0.87 and 0.91), and there was good agreement based on mean bias (-0.14 to 0.24 log10 copies/mL) and classification of VL above or below 1000 copies/mL (91.4% agreement). In contrast, VL from DBS was lower than plasma or PSC (mean bias 0.51 to 0.63 log10 copies/mL) and not as well correlated (r2 0.78 to 0.81, 75.1-80.5% agreement). These results confirm the utility of PSC as an alternative specimen type for HIV-1 viral load measurement in areas where preparation and optimal storage or shipment of plasma is an obstacle to provision of treatment and care of HIV-1 infected people.

Low-level viraemia: An emerging concern among people living with HIV in Uganda and across sub-Saharan Africa.

Attaining viral load (VL) suppression for over 95% of the people living with HIV on antiretroviral therapy is a fundamental step in enabling Uganda and other sub-Saharan African countries to achieve global Sustainable Development Goal targets to end the HIV/AIDS epidemic by 2030. In line with the 2013 World Health Organization recommendations, several sub-Saharan African countries, including Uganda, use a threshold of 1000 HIV viral RNA copies/mL to determine HIV viral non-suppression. The United States Centers for Disease Control and Prevention and the International Association of Providers of AIDS Care deem this threshold very high, and hence recommend using 200 copies/mL to determine viral non-suppression. Using 1000 copies/mL as a threshold ignores people living with HIV who have low-level viraemia (LLV; HIV VL of at least 50 copies/mL but less than 1000 copies/mL). Despite the 2021 World Health Organization recommendations of using intensive adherence counselling for people living with HIV with LLV, several sub-Saharan African countries have no interventions to address LLV. However, recent studies have associated LLV with increased risks of HIV drug resistance, virologic failure and transmission. The purpose of this narrative review is to provide insights on the emerging concern of LLV among people living with HIV receiving antiretroviral therapy in sub-Saharan Africa. The review also provides guidance for Uganda and other sub-Saharan African countries to implement immediate appropriate interventions like intensive adherence counselling, reducing VL thresholds for non-suppression and conducting more research to manage LLV which threatens progress towards ending HIV by 2030.

HIV viral load assays when used with whole blood perform well as a diagnostic assay for infants.

OBJECTIVE: Over the past several years, only approximately 50% of HIV-exposed infants received an early infant diagnosis test within the first two months of life. While high attrition and mortality account for some of the shortcomings in identifying HIV-infected infants early and putting them on life-saving treatment, fragmented and challenging laboratory systems are an added barrier. We sought to determine the accuracy of using HIV viral load assays for infant diagnosis of HIV. METHODS: We enrolled 866 Ugandan infants between March-April 2018 for this study after initial laboratory diagnosis. The median age was seven months, while 33% of infants were less than three months of age. Study testing was done using either the Roche or Abbott molecular technologies at the Central Public Health Laboratory. Dried blood spot samples were prepared according to manufacturer-recommended protocols for both the qualitative and quantitative assays. Viral load test samples for the Roche assay were processed using two different buffers: phosphate-buffered saline (PBS: free virus elution viral load protocol [FVE]) and Sample Pre-Extraction Reagent (SPEX: qualitative buffer). Dried blood spot samples were processed for both assays on the Abbott using the manufacturer's standard infant diagnosis protocol. All infants received a qualitative test for clinical management and additional paired quantitative tests. RESULTS: 858 infants were included in the analysis, of which 50% were female. Over 75% of mothers received antiretroviral therapy, while approximately 65% of infants received infant prophylaxis. The Roche SPEX and Abbott technologies had high sensitivity (>95%) and specificity (>98%). The Roche FVE had lower sensitivity (85%) and viral load values. CONCLUSIONS: To simplify and streamline laboratory practices, HIV viral load may be used to diagnose HIV infection in infants, particularly using the Roche SPEX and Abbott technologies.

The Consortium on Newborn Screening in Africa for sickle cell disease: study rationale and methodology.

Sickle cell disease (SCD) is a common condition within sub-Saharan Africa and associated with high under-5 mortality (U5M). The American Society of Hematology instituted the Consortium on Newborn Screening in Africa (CONSA) for SCD, a 7-country network of sites to implement standardized newborn hemoglobinopathy screening and early intervention for children with SCD in sub-Saharan Africa. CONSA's overall hypothesis is that early infant SCD screening and entry into standardized, continuous care will reduce U5M compared with historical estimates in the region. Primary trial objectives are to determine the population-based birth incidence of SCD and effectiveness of early standardized care for preventing early mortality consortium-wide at each country's site(s). Secondary objectives are to establish universal screening and early interventions for SCD within clinical networks of CONSA partners and assess trial implementation. Outcomes will be evaluated from data collected using a shared patient registry. Standardized trial procedures will be implemented among designated birth populations in 7 African countries whose programs met eligibility criteria. Treatment protocol includes administering antibacterial and antimalarial prophylaxis and standard childhood vaccinations against infections commonly affecting children with SCD. Infants with a positive screen and confirmation of SCD within the catchment areas defined by each consortium partner will be enrolled in the clinical intervention protocol and followed regularly until age of 5 years. Effectiveness of these early interventions, along with culturally appropriate family education and counseling, will be evaluated by comparing U5M in the enrolled cohort to estimated preprogram data. Here, we describe the methodology planned for this trial.

Implementing services for Early Infant Diagnosis (EID) of HIV: a comparative descriptive analysis of national programs in four countries.

BACKGROUND: There is a significant increase in survival for HIV-infected children who have early access to diagnosis and treatment. The goal of this multi-country review was to examine when and where HIV-exposed infants and children are being diagnosed, and whether the EID service is being maximally utilized to improve health outcomes for HIV-exposed children. METHODS: In four countries across Africa and Asia existing documents and data were reviewed and key informant interviews were conducted. EID testing data was gathered from the central testing laboratories and was then complemented by health facility level data extraction which took place using a standardized and validated questionnaire RESULTS: In the four countries reviewed from 2006 to 2009 EID sample volumes rose dramatically to an average of >100 samples per quarter in Cambodia and Senegal, >7,000 samples per quarter in Uganda, and >2,000 samples per quarter in Namibia. Geographic coverage of sites also rapidly expanded to 525 sites in Uganda, 205 in Namibia, 48 in Senegal, and 26 in Cambodia in 2009. However, only a small proportion of testing was done at lower-level health facilities: in Uganda Health Center IIs and IIIs comprised 47% of the EID collection sites, but only 11% of the total tests, and in Namibia 15% of EID sites collected >93% of all samples. In all countries except for Namibia, more than 50% of the EID testing was done after 2 months of age. Few sites had robust referral mechanisms between EID and ART. In a sub-sample of children, we noted significant attrition of infants along the continuum of care post testing. Only 22% (Senegal), 37% (Uganda), and 38% (Cambodia) of infants testing positive by PCR were subsequently initiated onto treatment. In Namibia, which had almost universal EID coverage, more than 70% of PCR-positive infants initiated ART in 2008. CONCLUSIONS: While EID testing has expanded dramatically, a large proportion of PCR- positive infants are initiated on treatment. As EID services continue to scale-up, more programmatic attention and support is needed to retain HIV-exposed infants in care and ensure that those testing positive initiate treatment in a timely manner. Namibia's experience demonstrates that it is feasible for a rural, low-income country to achieve high national coverage of infant testing and treatment.