HIV assessment and testing for hospital inpatients: still a weak link in the cascade

Since 2007, the World Health Organization has recommended that in countries with generalized HIV epidemics, HIV testing and counselling should be offered to all adults and adolescents seen in a health facility (1). This recommendation had been policy in Uganda since 2005 (2). However, evidence suggests that translation of this policy to practice in real-world settings has been patchy and that missed opportunities with HIV testing in the inpatient setting are still contributing to HIV related deaths (3,4)

Short Course for Focused Assessment with Sonography for Human Immunodeficiency Virus/Tuberculosis: Preliminary Results in a Rural Setting in South Africa with High Prevalence of Human Immunodeficiency Virus and Tuberculosis

In Africa, human immunodeficiency virus (HIV)–associated extrapulmonary tuberculosis (TB) is common and poses diagnostic difficulties. Ultrasound is useful to find suggestive signs such as effusions or abdominal lymphadenopathy. Because trained radiologists are scarce in resource-poor settings, even this simple and relatively inexpensive diagnostic tool is frequently unavailable to patients in district hospitals in sub-Saharan Africa. We developed a focused protocol for assessment with sonography for HIV/TB and trained physicians in a rural district hospital in South Africa. In this pilot study, high levels of confidence in identifying specific signs were rapidly achieved and ultrasound was introduced into routine clinical practice

HIV treatment cascade in tuberculosis patients

PURPOSE OF REVIEW: Globally, the number of deaths associated with tuberculosis (TB) and HIV coinfection remains unacceptably high. We review the evidence around the impact of strengthening the HIV treatment cascade in TB patients and explore recent findings about how best to deliver integrated TB/HIV services. RECENT FINDINGS: There is clear evidence that the timely provision of antiretroviral therapy (ART) reduces mortality in TB/HIV coinfected adults. Despite this, globally in 2013, only around a third of known HIV-positive TB cases were treated with ART. Although there is some recent evidence exploring the barriers to achieve high coverage of HIV testing and ART initiation in TB patients, our understanding of which factors are most important and how best to address these within different health systems remains incomplete. There are some examples of good practice in the delivery of integrated TB/HIV services to improve the HIV treatment cascade. However, evidence of the impact of such strategies is of relatively low quality for informing integrated TB/HIV programming more broadly. In most settings, there remain barriers to higher-level organizational and functional integration. SUMMARY: There remains a need for commitment to patient-centred integrated TB/HIV care in countries affected by the dual epidemic. There is a need for better quality evidence around how best to deliver integrated services to strengthen the HIV treatment cascade in TB patients, both at primary healthcare level and within community settings

Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort.

BACKGROUND: Better understanding of drug resistance patterns in HIV-infected children on antiretroviral therapy (ART) is required to inform public health policies in high prevalence settings. The aim of this study was to characterise the acquired drug resistance in HIV-infected children failing first-line ART in a decentralised rural HIV programme. METHODS: Plasma samples were collected from 101 paediatric patients (≤15 yrs of age) identified as failing ART. RNA was extracted from the plasma, reverse transcribed and a 1.3 kb region of the pol gene was amplified and sequenced using Sanger sequencing protocols. Sequences were edited in Geneious and drug resistance mutations were identified using the RegaDB and the Stanford resistance algorithms. The prevalence and frequency of mutations were analysed together with selected clinical and demographic data in STATA v11. RESULTS: A total of 101 children were enrolled and 89 (88%) were successfully genotyped; 73 on a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen and 16 on a protease inhibitor (PI)-based regimen at the time of genotyping. The majority of patients on an NNRTI regimen (80%) had both nucleoside reverse-transcriptase inhibitor (NRTI) and NNRTI resistance mutations. M184V and K103N were the most common mutations amongst children on NNRTI-based and M184V among children on PI-based regimens. 30.1% had one or more thymidine analogue mutation (TAM) and 6% had ≥3 TAMs. Only one child on a PI-based regimen harboured a major PI resistance mutation. CONCLUSIONS: Whilst the patterns of resistance were largely predictable, the few complex resistance patterns seen with NNRTI-based regimens and the absence of major PI mutations in children failing PI-based regimens suggest the need for wider access to genotypic resistance testing in this setting

HIV treatment cascade in tuberculosis patients.

PURPOSE OF REVIEW: Globally, the number of deaths associated with tuberculosis (TB) and HIV coinfection remains unacceptably high. We review the evidence around the impact of strengthening the HIV treatment cascade in TB patients and explore recent findings about how best to deliver integrated TB/HIV services. RECENT FINDINGS: There is clear evidence that the timely provision of antiretroviral therapy (ART) reduces mortality in TB/HIV coinfected adults. Despite this, globally in 2013, only around a third of known HIV-positive TB cases were treated with ART. Although there is some recent evidence exploring the barriers to achieve high coverage of HIV testing and ART initiation in TB patients, our understanding of which factors are most important and how best to address these within different health systems remains incomplete. There are some examples of good practice in the delivery of integrated TB/HIV services to improve the HIV treatment cascade. However, evidence of the impact of such strategies is of relatively low quality for informing integrated TB/HIV programming more broadly. In most settings, there remain barriers to higher-level organizational and functional integration. SUMMARY: There remains a need for commitment to patient-centred integrated TB/HIV care in countries affected by the dual epidemic. There is a need for better quality evidence around how best to deliver integrated services to strengthen the HIV treatment cascade in TB patients, both at primary healthcare level and within community settings

Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial

Background: Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes.Methods/design: A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters.Discussion: We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability. © 2013 Iwuji et al.; licensee BioMed Central Ltd

The tuberculosis challenge in a rural South African HIV programme.

BACKGROUND: South Africa remains the country with the greatest burden of HIV-infected individuals and the second highest estimated TB incidence per capita worldwide. Within South Africa, KwaZulu-Natal has one of the highest rates of TB incidence and an emerging epidemic of drug-resistant tuberculosis. METHODS: Review of records of consecutive HIV-infected people initiated onto ART between 1st January 2005 and 31st March 2006. Patients were screened for TB at initiation and incident episodes recorded. CD4 counts, viral loads and follow-up status were recorded; data was censored on 5th August 2008. Geographic cluster analysis was performed using spatial scanning. RESULTS: 801 patients were initiated. TB prevalence was 25.3%, associated with lower CD4 (AHR 2.61 p = 0.01 for CD4 25 copies/ml (OR 1.75 p = 0.11). A low-risk cluster for incident TB was identified for patients living near the local hospital in the geospatial analysis. CONCLUSION: There is a large burden of TB in this population. Rate of incident TB stabilises at a rate higher than that of the overall population. These data highlight the need for greater research on strategies for active case finding in rural settings and the need to focus on strengthening primary health care

Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study.

Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART

Southern African Treatment Resistance Network (SATuRN) RegaDB HIV drug resistance and clinical management database: supporting patient management, surveillance and research in southern Africa

Substantial amounts of data have been generated from patient management and academic exercises designed to better understand the human immunodeficiency virus (HIV) epidemic and design interventions to control it. A number of specialized databases have been designed to manage huge data sets from HIV cohort, vaccine, host genomic and drug resistance studies. Besides databases from cohort studies, most of the online databases contain limited curated data and are thus sequence repositories. HIV drug resistance has been shown to have a great potential to derail the progress made thus far through antiretroviral therapy. Thus, a lot of resources have been invested in generating drug resistance data for patient management and surveillance purposes. Unfortunately, most of the data currently available relate to subtype B even though >60% of the epidemic is caused by HIV-1 subtype C. A consortium of clinicians, scientists, public health experts and policy markers working in southern Africa came together and formed a network, the Southern African Treatment and Resistance Network (SATuRN), with the aim of increasing curated HIV-1 subtype C and tuberculosis drug resistance data. This article describes the HIV-1 data curation process using the SATuRN Rega database. The data curation is a manual and time-consuming process done by clinical, laboratory and data curation specialists. Access to the highly curated data sets is through applications that are reviewed by the SATuRN executive committee. Examples of research outputs from the analysis of the curated data include trends in the level of transmitted drug resistance in South Africa, analysis of the levels of acquired resistance among patients failing therapy and factors associated with the absence of genotypic evidence of drug resistance among patients failing therapy. All these studies have been important for informing first- and second-line therapy. This database is a free password-protected open source database available on www.bioafrica.net

Clinical outcomes after Viremia among people receiving dolutegravir vs efavirenz-based first-line antiretroviral therapy in South Africa

Background We aimed to compare clinical outcomes after viremia between dolutegravir vs efavirenz-based first-line antiretroviral therapy (ART) as evidence is lacking outside clinical trials in resource-limited settings. Methods We conducted a retrospective cohort analysis with routine data from 59 South African clinics. We included people with HIV aged ≥15 years receiving first-line tenofovir disoproxil fumarate, lamivudine, dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, efavirenz (TEE) and with first viremia (≥50 copies/mL) between June and November 2020. We used multivariable modified Poisson regression models to compare retention in care and viral suppression (<50 copies/mL) after 12 months between participants on TLD vs TEE. Results At first viremia, among 9657 participants, 6457 (66.9%) were female, and the median age (interquartile range [IQR]) was 37 (31–44) years; 7598 (78.7%) were receiving TEE and 2059 (21.3%) TLD. Retention in care was slightly higher in the TLD group (84.9%) than TEE (80.8%; adjusted risk ratio [aRR], 1.03; 95% CI, 1.00–1.06). Of 6569 participants retained in care with a 12-month viral load, viral suppression was similar between the TLD (78.9%) and TEE (78.8%) groups (aRR, 1.02; 95% CI, 0.98–1.05). However, 3368 participants changed ART during follow-up: the majority from TEE to first-line TLD (89.1%) or second-line (TLD 3.4%, zidovudine/emtricitabine/lopinavir-ritonavir 2.1%). In a sensitivity analysis among the remaining 3980 participants who did not change ART during follow-up and had a 12-month viral load, viral suppression was higher in the TLD (78.9%) than TEE (74.9%) group (aRR, 1.07; 95% CI, 1.03–1.12). Conclusions Among people with viremia on first-line ART, dolutegravir was associated with slightly better retention in care and similar or better viral suppression than efavirenz