Antiretroviral Treatment Program Research Articles

Deficiency of mannose-binding lectin is a risk of Pneumocystis jirovecii pneumonia in a natural history cohort of people living with HIV/AIDS in Northern Thailand.

Mannose-binding lectin (MBL) plays a pivotal role in innate immunity; however, its impact on susceptibility to opportunistic infections (OIs) has not yet been examined in a natural history cohort of people living with HIV/AIDS. We used archived samples to analyze the association between MBL expression types and risk of major OIs including Pneumocystis jirovecii pneumonia (PCP), cryptococcosis, talaromycosis, toxoplasmosis, and tuberculosis in a prospective cohort in Northern Thailand conducted from 1 July 2000 to 15 October 2002 before the national antiretroviral treatment programme was launched. Of 632 patients, PCP was diagnosed in 96 (15.2%) patients, including 45 patients with new episodes during the follow-up period (1006.5 person-years). The total history of PCP was significantly associated with low MBL expression type: high/intermediate (81/587, 13.8%), low (10/33, 30.3%) and deficient (5/12, 41.7%) (p = 0.001), whereas the history of other OIs showed no relation with any MBL expression type. Kaplan-Meier analysis (n = 569; log-rank p = 0.011) and Cox's proportional hazards model revealed that deficient genotype dramatically increased the risk of PCP, which is independent upon sex, age, CD4 count, HIV-1 viral load and hepatitis B and C status (adjusted hazard ratio 7.93, 95% confidence interval 2.19-28.67, p = 0.002). Deficiency of MBL expression is a strong risk factor determining the incidence of PCP but not other major OIs.

Community acceptability of dolutegravir-based HIV treatment in women: a qualitative study in South Africa and Uganda

BackgroundDespite concerns about dolutegravir use in pregnancy, most low- and middle-income countries are accelerating the introduction of dolutegravir-based regimens into national antiretroviral treatment programmes. Questions remain about the acceptability of dolutegravir use in women due to the potential risks in pregnancy. This study from South Africa and Uganda explored community values, preferences and attitudes towards the use of dolutegravir-based regimens in women.MethodsThis study employed a qualitative design involving in-depth interviews and focus group discussion conducted between August 2018 to March 2019. The study was conducted in the months following an announcement of a potential risk for neural tube defects with dolutegravir use among women during conception and the first trimester. Participants included HIV positive pregnant and lactating women and their partners. They were selected purposively from urban poor communities in South Africa and Uganda. Data was analysed thematically in NVivo.ResultsForty-four in-depth interviews and 15 focus group discussions were conducted. Most participants had positive views of dolutegravir-based regimens and perceived it to be more desirable compared with efavirenz-containing regimens. There was widespread concern about use of dolutegravir during pregnancy and among women of childbearing age due to publicity around the possible association with neural tube defects. Acceptability was gendered, with nearly all male participants preferring their female spouses of childbearing potential not to use dolutegravir, while most women not planning pregnancy wanted access to contraception alongside dolutegravir. Community awareness and knowledge of dolutegravir was low and characterised by negative information. Women were concerned about HIV-related stigma and wanted the privacy features of dolutegravir to be strengthened with modification of the pill appearance and disguised packaging.ConclusionsDolutegravir-based regimens were found to be generally acceptable for use in women except during pregnancy. Interest in a dolutegravir-based regimen was linked with its perceived potential to enhance health, privacy and reduce stigma while concerns about neural tube defects were the main potential barrier to dolutegravir uptake in women. In order to optimise the community acceptability and uptake of acceptability-based regimen among women it is critical to strengthen community awareness and understanding of dolutegravir treatment, improve contraception services alongside the introduction of dolutegravir, and engage with male partners.

Adult medical emergency unit presentations due to adverse drug reactions in a setting of high HIV prevalence.

IntroductionSouth Africa has the world's largest antiretroviral treatment programme, which may contribute to the adverse drug reaction (ADR) burden. We aimed to determine the proportion of adult non-trauma emergency unit (EU) presentations attributable to ADRs and to characterise ADR-related EU presentations, stratified according to HIV status, to determine the contribution of drugs used in management of HIV and its complications to ADR-related EU presentations, and identify factors associated with ADR-related EU presentation.MethodsWe conducted a retrospective folder review on a random 1.7% sample of presentations over a 12-month period in 2014/2015 to the EUs of two hospitals in Cape Town, South Africa. We identified potential ADRs with the help of a trigger tool. A multidisciplinary panel assessed potential ADRs for causality, severity, and preventability.ResultsWe included 1010 EU presentations and assessed 80/1010 (7.9%) as ADR-related, including 20/239 (8.4%) presentations among HIV-positive attendees. Among HIV-positive EU attendees with ADRs 17/20 (85%) were admitted, versus 22/60 (37%) of HIV-negative/unknown EU attendees. Only 5/21 (24%) ADRs in HIV-positive EU attendees were preventable, versus 24/63 (38%) in HIV-negative/unknown EU attendees. On multivariate analysis, only increasing drug count was associated with ADR-related EU presentation (adjusted odds ratio 1.10 per additional drug, 95% confidence interval 1.03 to 1.18), adjusted for age, sex, HIV status, comorbidity, and hospital.ConclusionsADRs caused a significant proportion of EU presentations, similar to findings from other resource-limited settings. The spectrum of ADR manifestations in our EUs reflects South Africa's colliding epidemics of infectious and non-communicable diseases. ADRs among HIV-positive EU attendees were more severe and less likely to be preventable.

Critical appraisal and external validation of a prognostic model for survival of people living with HIV/AIDS who underwent antiretroviral therapy

BackgroundHIV/AIDS remains a leading cause of death worldwide. Recently, a model has been developed in Wenzhou, China, to predict the survival of people living with HIV/AIDS (PLWHA) who underwent antiretroviral therapy (ART). We aimed to evaluate the methodological quality and validate the model in an external population-based cohort.MethodsPrediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess the risk of bias of the Wenzhou model. Data were from the National Free Antiretroviral Treatment Program database. We included PLWHA treated between February 2004 and December 2019 in a tertiary hospital in Guangzhou city, China. The endpoint was all-cause deaths and assessed until January 2020. We assessed the discrimination performance of the model by Harrell’s overall C-statistics and time-dependent C-statistics and calibration by comparing observed survival probabilities estimated with the Kaplan–Meier method versus predicted survival probabilities. To assess the potential prediction value of age and gender which were precluded in developing the Wenzhou model, we compared the discriminative ability of the original model with an extended model added with age and gender.ResultsBased on PROBAST, the Wenzhou model was rated as high risk of bias in three out of the four domains (selection of participants, definition of outcome, and methods for statistical analysis) mainly because of the misuse of nested case–control design and propensity score matching. In the external validation analysis, 16758 patients were included, among whom 743 patients died (mortality rate 11.41 per 1000 person-years) during follow-up (median 3.41 years, interquartile range 1.64–5.62). The predictor of HIV viral load was missing in 14361 patients (85.7%). The discriminative ability of the Wenzhou model decreased in the external dataset, with the Harrell’s overall C-statistics being 0.76, and time-dependent C-statistics dropping from 0.81 at 6 months to 0.48 at 10 years after ART initiation. The model consistently underestimated the survival, and the level was 6.23%, 10.02%, and 14.82% at 1, 2, and 3 years after ART initiation, respectively. The overall and time-dependent discriminative ability of the model improved after adding age and gender to the original model.ConclusionThe Wenzhou prognostic model is at high risk of bias in model development, with inadequate model performance in external validation. Thereby, we could not confirm the validity and extended utility of the Wenzhou model. Future prediction model development and validation studies need to comply with the methodological standards and guidelines specifically developed for prediction models.

The impact of the South African antiretroviral treatment programme on the age-standardised incidence rate of Kaposi sarcoma, 1999–2016: An interrupted time series analysis

ObjectiveThe objective of this study was to quantify the impact of the South African antiretroviral treatment programme on the age-standardised incidence rate of Kaposi sarcoma among black South African residents of all ages. MethodsWe performed an interrupted time series analysis using routinely collected, histologically confirmed surveillance data from the South African National Cancer Registry for the years 1999 to 2016. The analysis was performed using R statistical software. The total number of cases was 29,623 (12,475 females and 17,166 males). The background antiretroviral treatment coverage was less than 1% at the time that the antiretroviral programme was introduced and increased to over 50% in 2016. ResultsIn 1999, the age-standardised rates were 1.48 and 2.82 cases per 100,000 per year for black females and males, respectively. These rates increased to 5.52 and 7.46 in 2008 before declining. The antiretroviral treatment programme was started in 2004. Five years after 2008 (nine years after the antiretroviral programme was introduced), the predicted standardised rates were 58.3% and 50.3% lower for females and males, respectively, than what they would have been without the treatment programme. ConclusionIntroduction of the antiretroviral treatment programme was associated with a decrease of over 50% in the predicted age-standardised incidence rates of Kaposi sarcoma.

The dual protease inhibitor lopinavir/ritonavir (LPV/r) exerts genotoxic stress on lung cells

The Sub-Saharan countries, particularly South Africa has the largest number of people living with HIV, accompanied by the largest antiretroviral treatment (ART) programme in the world. The Highly Active Antiretroviral Treatment (HAART) is the most effective regimen against HIV/AIDS and has improved the lifespan and quality of life of HIV positive patients. HAART has also led to a decrease in the incidence of AIDS defining cancers (ADCs) while there is an increased incidence of the non-AIDS Defining Cancers (NADCs), such as lung cancer in the HAART era. The association between lung tumourigenesis and the use of HAART components such as the dual protease inhibitor (PI) lopinavir/ritonavir (LPV/r) is poorly understood. Using cell and molecular biological approaches, this study aimed at elucidating the effects of LPV/r on the regulation of the cell cycle related genes in normal (MRC-5) and adenocarcinoma (A549) lung cells. Initially, the nuclear integrity of these cells in response to LPV/r was determined using DAPI staining. The effect of LPV/r on cell cycle genes was evaluated through the use of a RT2 PCR gene array of 84 genes related to the cell cycle signaling pathway. The PCR array data was validated by Real-Time Quantification PCR (RT-qPCR). Ingenuity Pathway Analysis (IPA) bio-informatics tool was employed to disclose the molecular mechanism/s observed at cellular and gene expression levels. Loss of nuclear integrity and the upregulation of the p53 DNA damage response (DDR) pathway was revealed by DAPI staining, differential gene expression and IPA core analysis. Furthermore, MAD2L2 and AURKB which also play a role in the DDR pathway were shown to be differentially expressed. The activation of the CASP3 gene in response to LPV/r in A549 cells was also observed. The findings of this study suggest genotoxic properties of LPV/r in healthy normal lung fibroblasts cells and anti-tumour properties in the A549 cells.

Exploration of Long-term CD4 Profile in HIV Patients Under HAART at Mizan-Tepi University Teaching Hospital and Tepi General Hospital, South Western Ethiopia

Background : Currently, because of the wide availability and free service of HAART, HIV/AIDS related morbidity and mortality has decreased significantly. However, patients accessing antiretroviral treatment (ART) programmes in sub-Saharan Africa frequently have very advanced immunodeficiency and various reserches suggest that such patients may have diminished capacity for CD4 cell count recovery. The objective of this study was to investigate the long-term effect of highly active antiretroviral therapy on the CD4 lymphocyte count of HIV-infected Patients. Method : Subjects from the multicenter HAART Program cohort (from Mizan-Tepi University Teaching Hospital and Tepi General Hospital), aged 18 years or older and had an ART treatment start date in between February 1, 2017 to January 31, 2019 were enrolled in the present study and followed for a maximum of 3 years. Liner mixed model with nested random effect were used to model the longitudianl CD4 count over time. Result : The data reveal robust CD4 responses to ART that are continual over several years. Being under HAART for long period and having baseline CD4 count greater than 150 were postively associated with CD4 increment over time while starting ART at late stage (Stage 3 or 4) and being male are negatively assocted with CD4 increment over time. Conclusion : These data show strong and repetitive CD4 response to ART among patients remaining on therapy. Earlier HIV diagnosis and initiation of ART could significantly progress patient outcomes in the study area. Keywords: CD4counts, HAART, ART, Liner mixed model, Patients DOI: 10.7176/JNSR/11-19-02 Publication date: October 31 st 2020

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

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

Estimating retention in HIV care accounting for clinic transfers using electronic medical records: evidence from a large antiretroviral treatment programme in the Western Cape, South Africa.

Estimates of retention in antiretroviral treatment (ART) programmes may be biased if patients who transfer to healthcare clinics are misclassified as lost to follow-up (LTFU) at their original clinic. In a large cohort, we estimated retention in care accounting for patient transfers using medical records. Using linked electronic medical records, we followed adults living with HIV (PLWH) in Cape Town, South Africa from ART initiation (2012-2016) through database closure at 36months or 30 June 2016, whichever came first. Retention was defined as alive and with a healthcare visit in the 180days between database closure and administrative censoring on 31 December 2016. Participants who died or did not have a healthcare visit in >180days were censored at their last healthcare visit. We estimated the cumulative incidence of retention using Kaplan-Meier methods considering (i) only records from a participant's ART initiation clinic (not accounting for transfers) and (ii) all records (accounting for transfers), over time and by gender. We estimated risk differences and bootstrapped 95% confidence intervals to quantify misclassification in retention estimates due to patient transfers. We included 3406 PLWH initiating ART. Retention through 36months on ART rose from 45.4% (95% CI 43.6%, 47.2%) to 54.3% (95% CI 52.4%, 56.1%) after accounting for patient transfers. Overall, 8.9% (95% CI 8.1%, 9.7%) of participants were misclassified as LTFU due to patient transfers. Patient transfers can appreciably bias estimates of retention in HIV care. Electronic medical records can help quantify patient transfers and improve retention estimates.

Sex differences in HIV treatment outcomes and adherence by exposure groups among adults in Guangdong, China: A retrospective observational cohort study

IntroductionWe aimed to assess sex differences in treatment outcomes and adherence comparing men who have sex with women (MSW), men who have sex with men (MSM), and women who have sex with men (WSM), as well as men and women who inject drugs living with HIV on combination antiretroviral therapy (ART) in Guangdong, China. MethodsWe performed a retrospective observational cohort study with data from the National Free Antiretroviral Treatment Program database. We included ART-naive patients aged 18 to 80 years who had contracted HIV through sex or injecting drugs, initiated first-line ART between January 2004 and December 2016, and had at least 60 days of follow-up. Participants were followed for five years. Kaplan-Meier analysis and Cox proportional hazard models were used to evaluate all-cause mortality. Cumulative incidence function and Cox proportional hazards models accounting for competing risks were used to evaluate disease progression to AIDS. Modified Poisson regression models were used to evaluate immunological and virological responses and loss to follow-up. Repeated measures analysis was used to evaluate regular CD4+ cell count, HIV viral load monitoring, ART adherence, side effects, and interruption of ART. FindingsWe included 26,409 persons living with HIV. 21,779 (82·5%) people acquired HIV through sex (5118 WSM [23·5%], 8506 MSW [39·0%], 8175 MSM [37·5%]), and 4610 people (17·5%) through injection drug use (249 women [5·4%], 4361 men [94·6%]). Among those infected through sex, MSW had increased risks of all-cause mortality (adjusted hazard ratio [aHR] 1·48, 95% CI 1·20–1·83), progression to AIDS (1·27, 1·09–1·47), virological failure (adjusted incidence rates ratio [aIRR] 1·27, 95% CI 1·09–1·48), and loss to follow-up (1·22, 1·10–1·35) compared to WSM. In contrast, MSM had lower risk of all-cause mortality (aHR 0·49, 95%CI 0·32–0·76), disease progression to AIDS (0·83, 0·68–1·00), and virological failure (aIRR 0·78, 95%CI 0·65–0·94), were more likely to receive regular CD4+ cell count (1·08, 1·07–1·10) and HIV viral load monitoring (1·13, 1·12–1·15), were less likely to report missing ART doses (0·54, 0·49–0·61), interrupt ART (0·34, 0·26–0·44), or be lost to follow-up (0·56, 0·49–0·65) compared to WSM. Men who inject drugs were almost twice as likely as women who inject drugs to die (aHR 1·72, 95%CI 1·03–2·85), experience disease progression to AIDS (2·05, 1·18–3·57), virological failure (aIRR 1·81, 95%CI 1·19–2·76), report ART side effects (1·78, 1·43–2·22), and interruptions in ART (2·29, 1·50–3·50). InterpretationOur findings highlight the importance of identifying potentially at-risk MSW and promoting HIV education and testing among them. Particular attention is warranted among men who inject drugs to improve timely HIV diagnosis, drug interaction management, and retention in treatment. Additional research from rural settings is needed to assess the long-term treatment outcomes and adherence in MSM with HIV.

Risk factors for loss to follow-up from antiretroviral therapy programmes in low-income and middle-income countries.

Loss to follow-up (LTFU) rates from antiretroviral treatment (ART) programmes in low- and middle-income countries (LMIC) are high, leading to poor treatment outcomes and onward transmission of HIV. Knowledge of risk factors is required to address LTFU. In this systematic review, risk factors for LTFU are identified and meta-analyses performed. PubMed, Embase, Psycinfo and Cochrane were searched for studies that report on potential risk factors for LTFU in adults who initiated ART in LMICs. Meta-analysis was performed for risk factors evaluated by at least five studies. Pooled effect estimates and their 95% confidence intervals (95% CI) were calculated using random effect models with inverse variance weights. Risk of bias was assessed and sensitivity analyses performed. Eighty studies were included describing a total of 1 605 320 patients of which 87.4% from sub-Saharan Africa. The following determinants were significantly associated with an increased risk of LTFU in meta-analysis: male sex, older age, being single, unemployment, lower educational status, advanced WHO stage, low weight, worse functional status, poor adherence, nondisclosure, not receiving cotrimoxazole prophylactic therapy when indicated, receiving care at secondary level and more recent year of initiation. No association was seen for CD4 cell count, tuberculosis at baseline, regimen, and geographical setting. There are several sociodemographic, clinical, patient behaviour, treatment-related and system level risk factors for LTFU from ART programs. Knowledge of risk factors should be used to better target retention interventions and develop tools to identify high-risk patients.

Mental Health of Adolescents in the Era of Antiretroviral Therapy: Is There a Difference Between HIV-Infected and Uninfected Youth in South Africa?

PurposeThe HIV infection may predispose perinatally HIV-infected (PHIV+) adolescents to mental illness. Adolescence can be when mental health disorders manifest for the first time. This study investigates the prevalence of mental illness in PHIV+ and HIV-uninfected adolescents in Soweto. MethodsPHIV+ adolescents aged 13–19 years were recruited from an antiretroviral treatment program, whereas HIV-uninfected controls were recruited from the community in Soweto, South Africa, between October 2016 and April 2017. The Patient Health Questionnaire for Adolescents, Child Post-Traumatic Stress Disorder (PTSD) Checklist, and Millon Adolescent Clinical Inventory tools assessed components of mental health. Sociodemographic and virological data were collected. Risk factors for suicidality were determined by logistic regression. ResultsOne hundred and sixty-two adolescents (50% PHIV+, 61% female) with a median age of 16 years (interquartile range: 15–18) were enrolled. A depressive disorder was found in 14% of all adolescents, 35% had suicidal ideation, and 22% had PTSD symptoms. Risk factors for suicidality were female gender, HIV-positive status, repeating a grade at school and a history of physical and/or sexual abuse. ConclusionsThese findings show a high prevalence of suicidality and PTSD symptoms in adolescents from South Africa and highlight the importance of screening for mental illness, specifically suicidality, in HIV-positive adolescents. Adolescents from a disadvantaged socioeconomic background appear to be at risk, posing a challenge because of the lack of health seeking behaviors in young people and lack of adolescent-friendly health facilities. Interventions specific to adolescents in low- and middle-income countries are needed to improve emotional and psychiatric symptoms and functioning.

90-90-90 cascade analysis on reported CLHIV infected by mother-to-child transmission in Guangxi, China: a modeling study

The prevalence of HIV in Guangxi was very high, and there were many children living with HIV (CLHIV) because of larger baseline of pregnant women infected by HIV. It is necessary for children to explore the status of antiretroviral therapy (ART) on different initial CD4 counts in children with HIV infected by mother-to-child transmission (MTCT) in Guangxi and to evaluate the progress towards the 90-90-90 targets proposed by UNAIDS/WHO. Based on a retrospective observational cohort of children with HIV infected from the Guangxi Center for Disease Prevention and Control (CDC), the variables of all patients included viral loads, CD4 counts, laboratory results and WHO clinical staging of HIV/AIDS were collected. Several indicators were defined before analyzed: (1) diagnosis of MTCT: infants born to HIV-positive mothers who tested positive for HIV twice before 18 months; (2) ART initiation: the children who were enrolled in the treatment cohort and were still having HIV monitoring as of 6 months before date censored and (3) viral suppression: a recently viral load measurement that was less than 1000 copies per milliliter. The number of CLHIV in Guangxi was projected by using the estimates of the national HIV/AIDS prevalence from China CDC. An Autoregressive Integrated Moving Average (ARIMA) model and the Holt Exponential Smoothing (ES) model were used to predict the number of CLHIV, the diagnosed CLHIV, the diagnosed CLHIV receiving ART and the number of them achieving viral suppression, in 2019 and 2021, respectively. In this 14-year HIV/AIDS treatment cohort, 807 children who were HIV infected by MTCT were enrolled. The ARIMA and Holt ES models showed that by the end of 2019, 82.71% of all CLHIV in Guangxi knew their HIV status, 84.50% of those diagnosed had initiated ART, and 85.68% of those on ART had durable viral suppression. By the end of 2021, 93.51% of all CLHIV in Guangxi will know their HIV status, 84.28% of those diagnosed will have initiated antiretroviral therapy, and 85.83% of those on ART will have durable viral suppression. Therefore, in 2021, Guangxi fails to achieve the WHO/UNAIDS 90-90-90 targets for CLHIV, and there is still a wide time interval between the first HIV-positive diagnosis and ART initiation. National free antiretroviral treatment program (NFATP) requires strong enforcement to reduce the prevalence of later chronic diseases and complications.

Sinako, a study on HIV competent households in South Africa: a cluster-randomised controlled trial protocol

BackgroundWith 7.7 million South Africans currently infected with human immunodeficiency virus (HIV) and 4.8 million currently receiving antiretroviral treatment (ART), the epidemic represents a considerable burden for the country’s resource-limited health system. In response to the health and human resource shortages, task shifting to community health workers (CHWs) and empowering people living with HIV (PLWH) are integral parts of a sustainable ART strategy. Despite the success of the ART programme, South Africa still faces both prevention and treatment challenges. To tackle these challenges, future endeavours need to focus on the role played by the households of PLWH in mediating between the community and PLWH themselves. Building health-enabling “HIV competent” households with the capacity to actively stimulate lifestyles that foster health, offers a potential strategy to tackle South Africa’s HIV-related challenges. The aim of the “Sinako: Households and HIV” study is to investigate to what extent and how an intervention can increase HIV competence in PLWH and their households, and subsequently optimise the impact of CHW support on individual ART outcomes.MethodsThe “Sinako” study is a cluster-randomised controlled trial with two arms. In the control arm, CHWs offer a standard package of support to PLWH during home visits, focused on the individual. The intervention arm includes both a focus on the individual and the household to enable the patient to self-manage their treatment within an HIV competent household.A longitudinal mixed methods design is adopted to analyse the data. For the quantitative data analysis, methods including latent cross-lagged modelling, multilevel modelling and logistic regression will be used. To assess the acceptability and feasibility of the intervention and to construct a comprehensive picture of the mechanisms underlying the impact on the household and the PLWH, qualitative data (in-depth interviews and focus group discussions) will be collected and analysed.DiscussionStimulating HIV competence in households could be a feasible and sustainable strategy to optimise the outcomes of CHW interventions and thus be important for HIV treatment interventions in resource-limited settings.Trial registrationPan African Clinical Trial Registry, PACTR201906476052236. Registered on 24 June 2019.

Adaptation and biomedical transition of people living with HIV to antiretroviral treatment in Burkina Faso

ABSTRACTThis article examines the adaptation and biomedical transition of people living with HIV (PLHIV) to antiretroviral treatment (ART) in Burkina Faso. The study employs a representative sample of 3625 randomly selected patients. Subjective and objective measures of health and their predictors are compared for short-term (≤24 months) versus longer-term ART adherents (>24 months) in a cohort study. Subjective health is measured as Likert scale self-rating and objective health as CD4 count. The results show that subjective and objective health capture different aspects of adaptation to ART: 90% of the short-term and 94% of the longer-term patients give a subjective health rating of at least good, while the objective measure of good health is higher among longer-term (42%) compared to short-term patients (27%). For subjective health, short-lived pleasures are predictors among short-term adherents while economic characteristics are determinants among longer-term patients. Meanwhile, objective health is associated with factors that determine ART adherence (i.e. participating in self-help groups). To achieve a wholistic resilience management that caters to the needs of PLHIV, we need to acknowledge adaptation to the disease and to ART and design health programs, in particular in developing countries, away from one-size-fits-all solutions to stage-of-disease specific support.

Exploration of Long-term CD4 Profile in HIV Patients Under HAART at Mizan-Tepi University Teaching Hospital and Tepi General Hospital, South Western Ethiopia

Currently, because of the wide availability and free service of HAART, HIV/AIDS related morbidity and mortality has decreased significantly. However, patients accessing antiretroviral treatment (ART) programmes in sub-Saharan Africa frequently have very advanced immunodeficiency and various reserches suggest that such patients may have diminished capacity for CD4 cell count recovery. The objective of this study was to investigate the long-term effect of highly active antiretroviral therapy on the CD4 lymphocyte count of HIV-infected Patients. Subjects from the multicenter HAART Program cohort (from Mizan-Tepi University Teaching Hospital and Tepi General Hospital), aged 18 years or older and had an ART treatment start date in between February 1, 2017 to January 31, 2019 were enrolled in the present study and followed for a maximum of 3 years. Liner mixed model with nested random effect were used to model the longitudianl CD4 count over time. The data reveal robust CD4 responses to ART that are continual over several years. Being under HAART for long period and having baseline CD4 count greater than 150 were positively associated with CD4 increment over time while starting ART at late stage (Stage 3 or 4) and being male are negatively assocted with CD4 increment over time. These study show strong and repetitive CD4 response to ART among patients remaining on therapy. Earlier HIV diagnosis and initiation of ART could significantly progress patient outcomes in the study area.

Viral load assay performs comparably to early infant diagnosis assay to diagnose infants with HIV in Mozambique: a prospective observational study.

IntroductionViral load testing is essential to manage HIV disease, especially in infants and children. Early infant diagnosis is performed using nucleic‐acid testing in children under 18 months. Resource‐limited health systems face severe challenges to scale‐up both viral load and early infant diagnosis to unprecedented levels. Streamlining laboratory systems would be beneficial to improve access to quality testing and to increase efficiency of antiretroviral treatment programmes. We evaluated the performance of viral load testing to serve as an early infant diagnosis assay in children younger than 18 months.MethodsThis study was an observational, prospective study, including children between one and 18 months of age who were born to HIV‐positive mothers in 134 health facilities in Maputo City and Maputo Province, Mozambique. Dried blood spot specimens from heel or toe pricks were collected between January and April 2018, processed using SPEX buffer for both assays, and tested for routine EID and VL testing using the Roche CAP/CTM HIV‐1 Qualitative v2 and Roche CAP/CTM HIV‐1 Quantitative v2 assays respectively. The sensitivity, specificity and positive and negative predictive values were estimated using the EID results as the reference standard.ResultsA total of 1021 infants were included in the study, of which 47% were female. Over 95% of mothers and children were on antiretroviral treatment or received antiretroviral prophylaxis respectively. The sensitivity and specificity of using the viral load assay to detect infection were 100% (95% CI: 96.2 to 100%) and 99.9% (95% CI: 99.4 to 100%). The positive and negative predictive values were 99.0% (95% CI: 94.3 to 100%) and 100% (95% CI: 99.6 to 100%). The McNemar's test was 1.000 and Cohen's kappa was 0.994.ConclusionsThe comparable performance suggests that viral load assays can be used as an infant diagnostic assay. Infants with either low levels of viraemia or high cycle threshold values should be repeat tested to ensure the result is truly positive prior to treatment initiation, regardless of assay used. Viral load assays could replace traditional early infant diagnosis testing, substantially streamlining molecular laboratory services for children and lowering costs, with the additional advantage of providing baseline viral load results for antiretroviral treatment management.

Successful establishment of third-line antiretroviral therapy in Malawi: lessons learned.

Malawi has an extensive national antiretroviral treatment (ART) program, and although less than 2% of all patients receive second-line ART, there are increasingly more patients failing on these regimens. To establish a virtual ART committee using limited available local facilities and expertise to recommend third-line regimens based on genotype resistance of samples sent abroad. A secretariat and a laboratory sample hub were established. The committee started work after locally organizing training courses. Decisions about ART regimens were mainly based on a relatively simple, previously described algorithm, which allowed decisions to be taken without extensive expert knowledge. Of the 25 applications assessed, 23 samples were sent for resistance testing from June 2017 to April 2018. Major protease inhibitor (PI) resistance was detected in 65% of the samples. PI resistance was found even in patients exposed to PIs for short periods. In particular, patients who received co-administration of PIs and rifampicin frequently showed resistance mutations. Third-line ART using genotypic resistance testing and algorithm-based treatment regimens are feasible in low-resource settings. Our model can serve as a base for similar programs initiating programmatic third-line ART in other African countries.

Efficacy and Tolerability of Lopinavir/Ritonavir- and Efavirenz-Based Initial Antiretroviral Therapy in HIV-1-Infected Patients in a Tertiary Care Hospital in Beijing, China.

Background: Lopinavir/ritonavir (LPV/r) is a major antiretroviral treatment in China, but little is known about the performance of first-line LPV/r-based regimen in treatment-naïve patients with human immunodeficiency virus type 1 (HIV-1) infection. This study aims to assess the efficacy and adverse effect events of LPV/r plus lamivudine and tenofovir or zidovudine as an initial antiretroviral treatment in HIV-1-infected individuals for whom cannot take efavirenz (EFV) or is allergic to EFV.Methods: We performed a retrospective study of patients registering with the China’s National Free Antiretroviral Treatment Program from July 2012 to January 2017, followed at a tertiary care hospital in Beijing, China. The primary outcome was the proportion of subjects with HIV-1 RNA ≤40 copies/ml at 6 and 24 months of treatment. We assessed the immunological response and adverse events.Results: In total, 4,862 patients were enrolled in the study and 237 were eligible for analysis in each study arm. During the first six months, virological suppression was better with the LPV/r-based regimen than with the EFV-based regimen (93.80 vs 87.80% for P < 0.05). Viral suppression rates continued to increase until 12 months, remain steady thereafter until 24 months, for both groups. The multilevel analysis revealed that patients in the LPV/r group were more likely to display improvements in CD4 T-cell count over time than those in the EFV group (P < 0.001). Grade 3 or 4 laboratory adverse events were observed in 14 patients (5.91%) from the LPV/r group and three patients (1.20%) in EFV group.Conclusion: Our findings demonstrate that LPV/r-containing regimens are effective and well-tolerated in Chinese treatment-naïve patients with HIV-1 infection.

Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China.

Background: Pretreatment drug resistance (PDR) poses an increasing threat to the success of antiretroviral treatment (ART) programs in China. We aimed to conduct a survey of PDR among HIV patients in an area in Southwest China with extensive drug trafficking.Methods: Consecutive cross-sectional surveys were conducted in Liangshan Prefecture of Sichuan Province from 2009 to 2018 based on the WHO-recommended method. PDR was identified by testing pol region sequences with the Stanford HIVdb algorithm (version 7.0). PDR prevalence and related factors were assessed by multivariable logistic regression. The transmission of HIV drug resistance was analyzed using a genetic transmission network.Results: HIV-1 pol genes from 1889 patients were successfully amplified. The distribution of HIV-1 genotypes was as follows: CRF07_BC (94.0%), CRF08_BC (2.3%), CRF01_AE (2.0%) and others (1.4%). Of the participants, 6.9% (95% CI: 4.1-8.1%) had pretreatment resistance to 12 antiretroviral drugs recommended by the WHO, and nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitors (PI) resistance were identified among 1.4% (95% CI: 0.7-3.4%), 5.8% (95% CI: 1.2-8.7%) and 0.4% (95% CI: 0.1-3.0%) of the patients, respectively. In the multivariate logistic model, the prevalence of PDR was 1.52-fold higher among intravenous drug users (IDUs) than among patients infected by heterosexual transmission (95% CI: 1.07-2.38; P=0.049), and the prevalence of PDR among patients diagnosed from 2017-2018 was 2.03-fold higher than that among patients diagnosed from 2009-2016 (95% CI: 1.18-5.76; P=0.018). A total of 26 clusters containing PDR and a rapidly growing drug resistance-related cluster containing the E138Q and V179D mutations were identified by genetic transmission network analysis.Conclusion: The results show a moderate overall level of PDR prevalence and rapidly growing drug resistance over time. Preventive intervention should be focused on controlling the HIV epidemic among drug users, and surveillance is urgently needed to monitor the trend of PDR.