Recording of HIV viral loads and viral suppression in South African patients receiving antiretroviral treatment: a multicentre cohort study.
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ABSTRACT: Background
Viral suppression in patients on antiretroviral treatment (ART) is critical to reducing HIV transmission and HIV-related mortality. Although many studies have evaluated factors associated with viral suppression, few have assessed the extent to which missing viral load data may bias results.Methods
We included data on all patients starting ART from 2005 to 2019 in eight South African cohorts participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration. Multivariable logistic regression models were used to determine factors associated with having a viral load measurement within 2 months of a scheduled testing date and having a viral load <400 RNA copies/ml ('viral suppression'). In a sensitivity analysis, missing viral loads were imputed based on patients' clinical and demographic characteristics and outcomes.Results
Viral load tests were scheduled in 603,549 and 77,423 intervals in adults and children, respectively, but test results were recorded in only 40.7% and 41.2%, respectively. The proportion of recorded results suppressed was 85.7% in adults and 72.4% in children. After imputation of missing viral load measurements, viral suppression reduced slightly in adults (85.3%) and increased in children (73.2%). Predictors of virological suppression in adults, which included female sex, older age, higher baseline CD4+ T-cell count and recent testing year, were similar in the main analysis and after imputing missing viral loads.Conclusions
Although viral load information was frequently missing in the South African setting, estimates of viral suppression and predictors of viral suppression did not change substantially after adjusting for missing data.
SUBMITTER: Pillay T
PROVIDER: S-EPMC7982353 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hypermutation alludes to an excessive number of specific guanine-to-adenine (G- >A) substitutions in proviral DNA and this phenomenon is attributed to the catalytic activity of cellular APOBECs. Population studies relating hypermutation and the progression of infection by human immunodeficiency virus type 1 (HIV-1) have been performed to elucidate the effect of hypermutation on the natural course of HIV-1 infection. However, the many different approaches employed to assess hypermutation in nucleotide sequences render the comparison of results difficult. This study selected 157 treatment-naive patients and sought to correlate the hypermutation level of the proviral sequences in clinical samples with demographic variables, HIV-1 RNA viral load, and the level of CD4(+) T cells. Nested touchdown polymerase chain reaction (PCR) was performed with specific primers to detect hypermutation in the region of HIV-1 integrase, and the amplified sequences were run in agarose gels with HA-Yellow. The analysis of gel migration patterns using the k-means clustering method was validated by its agreement with the results obtained with the software Hypermut. Hypermutation was found in 31.2% of the investigated samples, and a correlation was observed between higher hypermutation levels and higher viral load levels. These findings suggest a high frequency of hypermutation detection in a Brazilian cohort, which can reflect a particular characteristic of this population, but also can result from the method approach by aiming at hypermutation-sensitive sites. Furthermore, we found that hypermutation events are pervasive during HIV-1 infection as a consequence of high viral replication, reflecting its role during disease progression.
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Project description:ObjectivesSouth Africa's national antiretroviral (ARV) treatment program expanded in 2010 to include the nucleoside reverse transcriptase (RT) inhibitors (NRTI) tenofovir (TDF) for adults and abacavir (ABC) for children. We investigated the associated changes in genotypic drug resistance patterns in patients with first-line ARV treatment failure since the introduction of these drugs, and protease inhibitor (PI) resistance patterns in patients who received ritonavir-boosted lopinavir (LPV/r)-containing therapy.MethodsWe analysed ARV treatment histories and HIV-1 RT and protease mutations in plasma samples submitted to the Tygerberg Academic Hospital National Health Service Laboratory.ResultsBetween 2006 and 2012, 1,667 plasma samples from 1,416 ARV-treated patients, including 588 children and infants, were submitted for genotypic resistance testing. Compared with 720 recipients of a d4T or AZT-containing first-line regimen, the 153 recipients of a TDF-containing first-line regimen were more likely to have the RT mutations K65R (46% vs 4.0%; p<0.001), Y115F (10% vs. 0.6%; p<0.001), L74VI (8.5% vs. 1.8%; p<0.001), and K70EGQ (7.8% vs. 0.4%) and recipients of an ABC-containing first-line regimen were more likely to have K65R (17% vs 4.0%; p<0.001), Y115F (30% vs 0.6%; p<0.001), and L74VI (56% vs 1.8%; p<0.001). Among the 490 LPV/r recipients, 55 (11%) had ?1 LPV-resistance mutations including 45 (9.6%) with intermediate or high-level LPV resistance. Low (20 patients) and intermediate (3 patients) darunavir (DRV) cross resistance was present in 23 (4.6%) patients.ConclusionsAmong patients experiencing virological failure on a first-line regimen containing two NRTI plus one NNRTI, the use of TDF in adults and ABC in children was associated with an increase in four major non- thymidine analogue mutations. In a minority of patients, LPV/r-use was associated with intermediate or high-level LPV resistance with predominantly low-level DRV cross-resistance.
| S-EPMC3694021 | biostudies-literature
Project description:IntroductionThere is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART).MethodsCompleteness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes.ResultsAfter exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults).ConclusionsSouth Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records.
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Project description:HIV treatment programs face challenges in identifying patients at risk for loss-to-follow-up and uncontrolled viremia. We applied predictive machine learning algorithms to anonymised, patient-level HIV programmatic data from two districts in South Africa, 2016-2018. We developed patient risk scores for two outcomes: (1) visit attendance ≤ 28 days of the next scheduled clinic visit and (2) suppression of the next HIV viral load (VL). Demographic, clinical, behavioral and laboratory data were investigated in multiple models as predictor variables of attending the next scheduled visit and VL results at the next test. Three classification algorithms (logistical regression, random forest and AdaBoost) were evaluated for building predictive models. Data were randomly sampled on a 70/30 split into a training and test set. The training set included a balanced set of positive and negative examples from which the classification algorithm could learn. The predictor variable data from the unseen test set were given to the model, and each predicted outcome was scored against known outcomes. Finally, we estimated performance metrics for each model in terms of sensitivity, specificity, positive and negative predictive value and area under the curve (AUC). In total, 445,636 patients were included in the retention model and 363,977 in the VL model. The predictive metric (AUC) ranged from 0.69 for attendance at the next scheduled visit to 0.76 for VL suppression, suggesting that the model correctly classified whether a scheduled visit would be attended in 2 of 3 patients and whether the VL result at the next test would be suppressed in approximately 3 of 4 patients. Variables that were important predictors of both outcomes included prior late visits, number of prior VL tests, time since their last visit, number of visits on their current regimen, age, and treatment duration. For retention, the number of visits at the current facility and the details of the next appointment date were also predictors, while for VL suppression, other predictors included the range of the previous VL value. Machine learning can identify HIV patients at risk for disengagement and unsuppressed VL. Predictive modeling can improve the targeting of interventions through differentiated models of care before patients disengage from treatment programmes, increasing cost-effectiveness and improving patient outcomes.
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Project description:IntroductionMental health problems are prevalent in adolescents living with HIV (ALHIV), often remain untreated, and may negatively affect antiretroviral therapy (ART) adherence and viral suppression. We implemented routine mental health screening at a paediatric ART clinic to improve the identification and management of mental health problems in ALHIV. In this report, we examine screening outcomes, associated patient characteristics and the odds of unsuppressed viral load in ALHIV screening positive for mental disorders.MethodsAdolescents aged 10 to 19 years attending Rahima Moosa Hospital in Johannesburg, South Africa between February 1, 2018, and January 1, 2020, were offered mental health screening at each routine HIV care visit. The screening included four pre-screening questions followed by full screening (conditional on positive pre-screening) for depression (Patient Health Questionnaire-9 [PHQ-9]), suicide (Adolescent Innovations Project [AIP]-handbook), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), post-traumatic stress disorder (PTSD) (Primary Care PTSD Screen [PC-PTSD-5]) and substance use (CAGE Adapted to Include Drugs [CAGE-AID]). We assessed screening outcomes and calculated adjusted odds ratios for associations between positive screening tests at the first screen and unsuppressed viral load (>400 copies/mL) at the measurement taken closest to the date of screening, within hundred days before and one day after screening.ResultsOut of 1203 adolescents who attended the clinic, 1088 (90.4%) were pre-screened of whom 381 (35.0%) underwent full screening, 48 (4.4%) screened positive for depression (PHQ-9 ≥10), 29 (2.8%) for suicidal concern, 24 (2.2%) for anxiety (GAD-7 ≥10), 38 (3.2%) for PTSD (PC-PTSD-5 ≥3), 18 (1.7%) for substance use (CAGE-AID ≥2) and 97 (8.9%) for any of these conditions. Positive screening for depression (aOR 2.39, 95% CI 1.02 to 5.62), PTSD (aOR 3.18, 95% CI 1.11 to 9.07), substance use (aOR 7.13, 95% CI 1.60 to 31.86), or any condition (aOR 2.17, 95% CI 1.17 to 4.02) were strongly associated with unsuppressed viral load.ConclusionsALHIV affected by mental health problems have increased rates of unsuppressed viral load and need specific clinical attention. The integration of routine mental health screening in paediatric ART programmes is a feasible approach for identifying and referring adolescents with mental health and adherence problems to counselling and psychosocial support services and if needed to psychiatric care.
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Project description:OBJECTIVE:African-American women are more likely than other women in the United States to experience poor HIV-related health; HIV stigma may contribute to these outcomes. This study assessed the relationship between HIV stigma and viral load, over time, among a sample of African-American women receiving treatment for HIV, and explored social support and depressive symptoms as mediators. DESIGN:Secondary analysis of longitudinal data. METHODS:Data came from a randomized trial of an intervention to reduce HIV stigma among African-American women in HIV care in Chicago, Illinois and Birmingham, Alabama. Sociodemographic and psychosocial data were collected at up to six study visits over 14 months. Viral loads were extracted from medical records during the study period. Generalized linear mixed effects models were used to estimate associations among overall, internalized, and enacted HIV stigma and viral load over time. Mediation analyses were used to estimate indirect effects via social support and depressive symptoms. RESULTS:Data from 234 women were analyzed. Overall HIV stigma was significantly associated with subsequent viral load (adjusted β = 0.24, P = 0.005). Both between-subject (adjusted β = 0.74, P < 0.001) and within-subject (adjusted β = 0.34, P = 0.005) differences in enacted stigma were associated with viral load. Neither social support nor depressive symptoms were statistically significant mediators. CONCLUSION:Ongoing experiences of HIV stigmatization may contribute to increased viral load among African-American women in primary HIV care. Interventions should aim to alleviate the consequences of stigma experienced by patients and prevent future stigmatization.
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Project description:BackgroundIncreased availability of HIV care over the past decade has dramatically reduced morbidity and mortality among people living with HIV (PLWH) in sub-Saharan Africa. However, perceived and experienced barriers to care, including dissatisfaction with services, may impact adherence and viral suppression. We examined the associations between satisfaction with HIV care and antiretroviral therapy (ART) adherence and viral load suppression.MethodsThe African Cohort Study (AFRICOS) is a prospective observational study conducted at PEPFAR-supported clinics in four African countries. At enrollment and twice-yearly study visits, participants received a clinical assessment and a socio-behavioral questionnaire was administered. Participants were classified as dissatisfied with care if they reported dissatisfaction with any of the following: waiting time, health care worker skills, health care worker attitudes, quality of clinic building, or overall quality of care received. Robust Poisson regression was used to estimate prevalence ratios and 95% confidence intervals (CIs) for associations between satisfaction with care and ART adherence and between satisfaction with care and viral suppression (viral load < 1000 copies/mL).ResultsAs of 1 March 2020, 2928 PLWH were enrolled and 2311 had a year of follow-up visits. At the first annual follow-up visit, 2309 participants responded to questions regarding satisfaction with quality of care, and 2069 (89.6%) reported satisfaction with care. Dissatisfaction with waiting time was reported by 177 (7.6%), building quality by 59 (2.6%), overall quality of care by 18 (0.8%), health care worker attitudes by 16 (0.7%), and health care worker skills by 15 (0.7%). After adjusting for age and site, there was no significant difference in viral suppression between those who were satisfied with care and those who were dissatisfied (aPR: 1.03, 95% CI 0.97-1.09). Satisfaction with HIV care was moderately associated with ART adherence among AFRICOS participants (aPR: 1.09; 95% CI 1.00-1.16).ConclusionsWhile patient satisfaction in AFRICOS was high and the association between perceived quality of care and adherence to ART was marginal, we did identify potential target areas for HIV care improvement, including reducing clinic waiting times.
| S-EPMC8614053 | biostudies-literature
Project description:BackgroundAccurately identifying individuals who are on antiretroviral therapy (ART) is important to determine ART coverage and proportion on ART who are virally suppressed. ART is also included in recent infection testing algorithms used to estimate incidence. We compared estimates of ART coverage, viral load suppression rates and HIV incidence using ART self-report and detection of antiretroviral (ARV) drugs and we identified factors associated with discordance between the methods.MethodsCross-sectional population-based survey in KwaZulu-Natal, South Africa. Individuals 15-59 years were eligible. Interviews included questions about ARV use. Rapid HIV testing was performed at the participants' home. Blood specimens were collected for ARV detection, LAg-Avidity HIV incidence testing and viral load quantification in HIV-positive individuals. Multivariate logistic regression models were used to identify socio-demographic covariates associated with discordance between self-reported ART and ARV detection.ResultsOf the 5649 individuals surveyed, 1423 were HIV-positive. Median age was 34 years and 76.3% were women. ART coverage was estimated at 51.4% (95%CI:48.5-54.3), 53.1% (95%CI:50.2-55.9) and 56.1% (95%CI:53.5-58.8) using self-reported ART, ARV detection and both methods combined (classified as ART exposed if ARV detected and/or ART reported) respectively. ART coverage estimates using the 3 methods were fairly similar within sex and age categories except in individuals aged 15-19 years: 33.3% (95%CI:23.3-45.2), 33.8% (95%CI:23.9-45.4%) and 44.3% (95%CI:39.3-46.7) using self-reported ART, ARV detection and both methods combined. Viral suppression below 1000cp/mL in individuals on ART was estimated at 89.8% (95%CI:87.3-91.9), 93.1% (95%CI:91.0-94.8) and 88.7% (95%CI:86.2-90.7) using self-reported ART, ARV detection and both methods combined respectively. HIV incidence was estimated at 1.4 (95%CI:0.8-2.0) new cases/100 person-years when employing no measure of ARV use, 1.1/100PY (95%CI:0.6-1.7) using self-reported ART, and 1.2/100PY (95%CI:0.7-1.7) using ARV detection. In multivariate analyses, individuals aged 15-19 years had a higher risk of discordance on measures of ARV exposure (aOR:9.4; 95%CI:3.9-22.8), while migrants had a lower risk (aOR:0.3; 95%CI:0.1-0.6).ConclusionsIn KwaZulu-Natal, the method of identifying ARV use had little impact on estimates of ART coverage, viral suppression rate and HIV incidence. However, discordant results were more common in younger individuals. This may skew estimates of ART coverage and viral suppression, particularly in adolescent surveys.
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