Understanding the BED capture enzyme immunoassay (CEIA): measuring HIV-1 incidence in cross-sectional studies

Thesis (Ph.D.(Public Health))--University of the Witwatersrand, Faculty of Health Sciences, 2012.Measuring HIV incidence has proved challenging over the years. A number of serological HIV assays have been proposed, and among these, the BED Capture Enzyme Immunoassay (CEIA) is one of the more widely used. Although the assay performs well among known seroconverting panels, it has been shown to classify some long term infected patients as being recently infected. Information on the performance of the BED assay among low CD4 cell count patients and those on antiretroviral therapy is limited. The risk of onwards transmission of HIV has been reported to be elevated around the seroconversion period compared to the chronic stage of infection. RNA viral load has been reported as the strongest predictor of HIV transmission compared to other HIV markers. Understanding how these markers influence the relationship between the likelihood of being recently infected and the BED assay might help in understanding some of the shortcomings of the BED assay. The main aim of this study was to understand the properties of the BED assay. The performance of the BED assay among advanced HIV disease patients and the influence of ART on BED levels once patients started treatment was investigated. The BED assay and CD4 cell count were used to quantify the risk of in utero and intrapartum transmission to their infants among women believed to have seroconverted during pregnancy. The influence of viral load, haemoglobin and mid-upper arm circumference was investigated on the relationship between the probability of being recently infected and BED ODn levels. Methods Cryopreserved plasma samples from HIV patients on the national antiretroviral treatment (ART) rollout programme at Tygerberg Hospital HIV clinic, South Africa, iv were used to investigate the effect of ART on BED ODn levels once patients commenced treatment. Mixed effect logistic regression models accounting for multiple readings per patient were used. To investigate the risk associated with seroconversion during pregnancy HIV seropositive women who had just given birth were classified into mutually exclusive groups according to their likelihood of having recently seroconverted using BED and CD4 cell count levels. Multinomial logistic regression models adjusting for other factors were used to assess the risk of MTCT in utero and intra-partum infection comparing these groups. To investigate the relationship between BED ODn levels and the probability of being recently infected, BED data from known HIV infected women and women who seroconverted over a 2 year period was used. Fractional polynomial regression models that allow for non-linear functions to be fitted were used, and the influence of viral load, haemoglobin and mid-upper arm circumference was assessed through multi-variable models. Data from the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) project, a double blinded treatment-placebo trial was used for these last two objectives. Results Patients with very low CD4 cell counts were more likely to test false recently infected according to the BED assay than other patients. ART changed BED ODn kinetics among HIV patients on treatment. Over half of advanced disease stage patients were likely to be classified as being recently infected according to the BED assay 2 years into ART treatment. v Women who seemed to have seroconverted during pregnancy had elevated risk of transmitting HIV in-utero compared to chronic HIV patients. BED and CD4 cell count were not predictive of risk of intra-partum infections attributed to seroconversion during pregnancy. The relationship between the probability of being recently infected with HIV and BED ODn levels was described better using Fractional Polynomial regression models than using a linear model in BED ODn or a model in which the BED ODn was categorised. Viral load and haemoglobin were important independent predictors of incident infections. Conclusions If the BED assay is to be used for HIV incidence estimations patients on ART should be accounted for. The BED assay together with other HIV serological markers can be used as prognostic tools to assess the risk of HIV transmission. The risk of in-utero transmission of HIV is higher among women who seroconvert during pregnancy. Repeat HIV testing among pregnant women may help in identifying women who seroconvert during pregnancy, and these women will benefit from Prevention of Mother-to-Child transmission (PMTCT) programmes. It was found that additional markers such as viral load and haemoglobin did not alter the relationship between the probability of having been recently infected and BED ODn

Towards achieving the 90–90–90 HIV targets: Results from the south African 2017 national HIV survey

Background: Measuring progress towards the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90–90–90 treatment targets is key to assessing progress towards turning the HIV epidemic tide. In 2017, the UNAIDS model estimated that 75% of people living with HIV (PLHIV) globally knew their HIV positive status, 79% of those who knew their status were on antiretroviral therapy (ART), and 81% of those who knew their HIV status and were on ART had a suppressed viral load. The fifth South African national HIV sero-behavioural survey collected nationally representative data that enabled the empirical estimation of these 90–90–90 targets for the country stratified by a variety of key factors. Methods: To evaluate progress towards achievement of the 90–90–90 targets for South Africa, data obtained from a national, representative, cross-sectional population-based multi-stage stratified cluster random survey conducted in 2017 were analysed. The Fifth South African National HIV Prevalence, Incidence, Behaviour and Communication Survey (SABSSM V), collected behavioural and biomarker data from individuals residing in households from 1000 randomly selected Small Area Layers (SALs), across all nine provinces of the country. Structured questionnaires were used to collect socio-demographic data, knowledge and perceptions about HIV, and related risk behaviours

Assessing spatial patterns of HIV prevalence and interventions in semi-urban settings in South Africa. Implications for spatially targeted interventions

DATA AVAILABITY STATEMENT : The data presented in this study are available on request from the corresponding author. The data are not publicly available as permission from the gatekeepers is required for access.Equitable allocation of resources targeting the human immunodeficiency virus (HIV) at the local level requires focusing interventions in areas of the greatest need. Understanding the geographical variation in the HIV epidemic and uptake of selected HIV prevention and treatment programmes are necessary to identify such areas. Individual-level HIV data were obtained from a 2012 national HIV survey in South Africa. Spatial regression models on each outcome measure (HIV infection, sub-optimal condom use or non-anti-retroviral treatment (ART) adjusted for spatial random effects at the ward level were fitted using WINBUGS software. In addition, ward-level data was utilized to estimate condom use coverage and ART initiation rates which were obtained from routinely collected data in 2012. Ordinary Kriging was used to produce smoothed maps of HIV infection, condom use coverage and ART initiation rates. HIV infection was associated with individuals undertaking tertiary education [posterior odds ratio (POR): 19.53; 95% credible intervals (CrI): 3.22- 84.93]. Sub-optimal condom use increased with age (POR: 1.09; 95%CrI: 1.06-1.11) and was associated with being married (POR: 4.14; 95%CrI: 1.23-4.28). Non-ART use was associated with being married (POR: 6.79; 95%CrI: 1.43-22.43). There were clusters with high HIV infection, sub-optimal condom use, and non- ART use in Ekurhuleni, an urban and semi-urban district in Gauteng province, South Africa. Findings show the need for expanding condom programmes and/or strengthening other HIV prevention programmes such as pre-exposure prophylaxis and encouraging sustained engagement in HIV care and treatment in the identified areas with the greatest need in Ekurhuleni Metropolitan Municipality.This PhD work is based on the research supported by the Department of Science and Innovation and the National Research Foundation (NRF).https://www.geospatialhealth.net/index.php/ghhj2023Statistic

Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study

Objectives To estimate the rates and timing of mother to infant transmission of HIV associated with breast feeding in mothers who seroconvert postnatally, and their breast milk and plasma HIV loads during and following seroconversion, compared with women who tested HIV positive at delivery

Association between ART adherence and mental health : results from a national HIV sero-behavioural survey in South Africa

This paper assesses the levels of antiretroviral treatment (ART) adherence and mental health distress among study participants in a national behavioural HIV-sero prevalence study South Africa. The study was a cross-sectional population-based multi-stage stratified cluster random survey, (SABSSM V, 2017). Structured questionnaires were used to collect information on socio-demographics, HIV knowledge, perceptions, HIV testing and HIV treatment history. Study participants were tested for HIV infection, antiretroviral use, viral suppression, and ART drug resistance. A total of 2155 PLHIV aged 15 years or older who were on ART were included in the study. Incidence of either moderate or severe mental health distress was 19.7%. Self-reported ART adherence among study participants with no, mild, moderate, or severe mental distress was 82%, 83%, 86% and 78%, respectively. The adjusted odds ratio for ART non-adherence was 0.58 (95% CI 0.24; 1.40) for mild mental distress, 0.82 (95% CI 0.35; 1.91) for moderate mental distress and 2.19 (95% CI 1.14; 4.19) for severe mental distress groups compared to the no mental health distress group. The other factors that were associated with ART non-adherence in adjusted models included education level, alcohol use and province/region of residence. The study revealed that mental health remains a challenge to ART adherence in South Africa. To improve ART adherence, HIV continuum of care programs should include screening for mental health among people living with HIV.The President’s Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention under the terms of Cooperative Agreement Number NU2GGH001629. Additional funding was also received from the South African Department of Science and Technology (now known as the Department of Science and Innovation), South African National AIDS Council, The Global Fund to Fight AIDS, Tuberculosis and Malaria, Right to Care, United Nations Children’s Fund (UNICEF), the Centre for Communication Impact, Soul City, and love Life.http://link.springer.com/journal/10461hj2023Psycholog

Is there risk compensation among HIV infected youth and adults 15 years and older on antiretroviral treatment in South Africa? findings from the 2017 national HIV prevalence, incidence, behaviour and communication survey

In this paper, risk compensation among individuals on antiretroviral therapy (ART), using the 2017 South African national survey on HIV, is explored. A multi-stage stratified cluster random sampling approach was used to realize 11,130 participants 15 years and older. Logistic regression analysis assessed the association between multiple sexual partners, condom use at last sexual encounter, consistency of condom usage and potential explanatory variables using HIV status and ART exposure as a mediator variable. HIV positive participants who were aware and on ART were less likely to have multiple sexual partners, and less likely not to use a condom at last sex compared to HIV positive participants who were aware but not on ART. The odds of reporting multiple sexual partners were significantly lower among older age groups, females, non-Black Africans, and rural settings, and higher among those with tertiary level education, and risky alcohol users. The odds of no condom use at last sexual encounter were more likely among older age groups, females, other race groups, and less likely among those with secondary level education. The odds of inconsistent condom use were more likely among older age groups, females, and other race groups, and less likely among those with tertiary level education, high risk and hazardous alcohol users. Risk compensation is not apparent among HIV infected adults who are on ART. Risk groups that should receive tailored interventions to reduced risky sexual behaviours were identified.DATA AVAILABILITY STATEMENT : The data for this manuscript are openly available on the Human Sciences Research Council institutional repository available at https://repository.hsrc.ac.za/handle/20.500.119 10/15468, Archive number: SABSSM 2017 Combined, URI: http://doi.org/10.14749/1585345902.President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) Cooperative Agreement.https://www.mdpi.com/journal/ijerphPsycholog

Predictors of loss to follow-up among children in the first and second years of antiretroviral treatment in Johannesburg, South Africa

Background: Ninety percent of the world's 2.1 million HIV-infected children live in sub-Saharan Africa, and 2.5% of South African children live with HIV. As HIV care and treatment programmes are scaled-up, a rise in loss to follow-up (LTFU) has been observed. Objective: The aim of the study was to determine the rate of LTFU in children receiving antiretroviral treatment (ART) and to identify baseline characteristics associated with LTFU in the first year of treatment. We also explored the effect of patient characteristics at 12 months treatment on LTFU in the second year. Methods: The study is an analysis of prospectively collected routine data of HIV-infected children at the Harriet Shezi Children's Clinic (HSCC) in Soweto, Johannesburg. Cox proportional hazards models were fitted to investigate associations between baseline characteristics and 12-month characteristics with LTFU in the first and second year on ART, respectively. Results: The cumulative probability of LTFU at 12 months was 7.3% (95% CI 7.1–8.8). In the first 12 months on ART, independent predictors of LTFU were age <1 year at initiation, recent year of ART start, mother as a primary caregiver, and being underweight (WAZ ≤ −2). Among children still on treatment at 1 year from ART initiation, characteristics that predicted LTFU within the second year were recent year of ART start, mother as a primary caregiver, being underweight (WAZ ≤ −2), and low CD4 cell percentage. Conclusions: There are similarities between the known predictors of death and the predictors of LTFU in the first and second years of ART. Knowing the vital status of children is important to determine LTFU. Although HIV-positive children cared for by their mothers appear to be at greater risk of becoming LTFU, further research is needed to explore the challenges faced by mothers and other caregivers and their impact on long-term HIV care. There is also a need to investigate the effects of differential access to ART between mothers and children and its impact on ART outcomes in children

A pilot study assessing the impact of a fortified supplementary food on the health and well-being of crèche children and adult TB patients in South Africa.

The South African population faces many of the global concerns relating to micronutrient deficiency and the impact this has on health and well-being. Moreover, there is a high prevalence of HIV infection, compounded by a high level of co-infection with TB.This pilot study evaluates the impact of a fortified supplementary food on the health and well-being of a cohort of crèche children, aged 3 to 6, and adult TB patients drawn from the Presidential Node of Alexandra, Johannesburg, South Africa. A further aim of this study was to evaluate the sensitivity and validity of non-invasive indicators of nutritional status in a field-based population sample.The investigational product, e'Pap, is supported by extensive anecdotal evidence that whole grain cereals with food-style nutrients constitute an effective supplementary food for those suffering from the effects of food insecurity, poor health and well-being, and coping with TB and HIV infection.The results indicate a beneficial effect of e'Pap for both study populations, and particularly for adult TB patients, whose baseline data reflected severe food insecurity and malnutrition in the majority of cases. There is evidence to suggest statistically significant improvements in key micronutrient levels, well-being and energy, hand-grip strength, the Bioelectrical Impedance Analysis (BIA) Illness Marker, and certain clinical indicators. Although Body Mass Index (BMI) and Mid Upper Arm Circumference (MUAC) are frequently used as standard measures to evaluate the efficacy of nutritional interventions, these indicators were not sufficiently sensitive in this study. Nor does weight gain necessarily indicate improved nutritional status. Hand-grip strength, lean body mass, and the BIA Illness Marker seem to be more useful indicators of change in nutritional status

Data and analysis scripts: Amitriptyline for the management of painful HIV-associated sensory neuropathy (HIV-SN)

<p><b>Citation: </b>Dinat N, Marinda E, Moch S, Rice AS, Kamerman PR. Randomized, double-blind, crossover trial of amitriptyline for analgesia in painful HIV-associated sensory neuropathy. PLoS One 10(5):e0126297. DOI:10.1371/journal.pone.0126297, PMID: 25974287</p><p><b>Repo content: </b>Data, codebooks, and analysis scripts for a randomized, double-blind, placebo-controlled, cross-over clinical trial of amitriptyline for the management of moderate to severe pain associated with HIV-associated sensory neuropathy. </p><p><b>Background and study aims: </b>The peripheral nervous system is part of the nervous system that is made up of the nerves and ganglia (group of nerve cells) outside of the brain and spinal cord (the central nervous system). It connects the central nervous system to the limbs and organs of the body. Damage to peripheral nerves, especially the long nerves of the feet and hands, is common in people infected with HIV. This damage may be caused by the virus itself, some of the antiretroviral drugs used to treat HIV/AIDS, or as a result of opportunistic infections, for example thrush, herpes and tuberculosis. The nerve damage is often painful, can have a detrimental effect on a person's quality of life and has significant socioeconomic effects. Unlike other types of peripheral neuropathy (e.g., the neuropathy that develops in people with diabetes mellitus), there are, as yet, no effective treatments for painful HIV neuropathy. Here, we want to see if amitriptyline, an antidepressant drug that has been shown to relieve pain in other types of neuropathy, can provide pain relief better than that of a placebo (a dummy pill) in patients with painful HIV neuropathy. </p><p><b>Who participated? </b>Adult HIV-infected individuals that have been diagnosed with painful HIV-associated sensory </p><p>neuropathy. Participants were either be on stable antiretroviral therapy, or had never been exposed to antiretroviral therapy for HIV infection.</p><p><b>What did the study involve? </b>Ambulatory HIV-positive patients attending clinics at Chris Hani Baragwanath Hospital, Soweto, South Africa were randomly allocated to receive amitriptyline (25-150mg/day) or a placebo for six weeks. The drug/placebo dose was started at 25mg/day and increased every three days over the first two weeks of the treatment until participants achieve pain relief, intolerable side effects, or a maximum dose of 150 mg/day. The trial drug and the placebo were identical in appearance. Participants visit the study centre every three weeks to receive their medication and to record a pain score. At the end of the first six-week treatment period, participants are taken off their assigned medication for a three-week 'washout' period. After this washout period, those participants who receive amitriptyline before were now given the placebo and vice versa for another 6 weeks. Dose titration and pain assessments followed the same protocol used in the first six-week period.</p><p><b>Where was the study run from? </b>Nthabiseng HIV Clinic and the Centre for Palliative Care, Chris Hani Baragwanath Hospital, Soweto, South Africa</p><p><b>What was the study outcome? </b>Amitriptyline was not superior to placebo at relieving moderate-to-severe pain in individuals with HIV-SN.</p><p><br></p

CONSORT diagram illustrating participant flow during the study.

<p>The two randomized participants whose data were excluded from the analysis dropped out of the trial for non-trial related reasons: one participant (ARV-user) was disenrolled from the study to start tuberculosis therapy after her test results, which had been misplaced and then found, showed that she had active pulmonary tuberculosis; and one participant (ARV-naive) was lost to follow-up after being hospitalized for the treatment of community acquired pneumonia.</p