Search

: Introduction: People living with HIV (PLWH) have higher rates of non‐infectious comorbid diseases (NCDs) than individuals without HIV. We characterized the risk of NCDs among PLWH with undetectable viral load and persistent low‐level viraemia (pLLV) in the African Cohort Study (AFRICOS). We secondarily quantified the role of immune activation in the association between LLV and NCDs. Methods: AFRICOS enrols participants in 12 clinics in Uganda, Kenya, Tanzania and Nigeria. Participants on antiretroviral therapy ≥ 6 months without an NCD at enrolment were included. PLLV was defined as at least two consecutive visits with a detectable viral load Results: From 23 January 2013 to 1 December 2022, 1755 participants met the inclusion criteria for these analyses. At the first eligible visit, the majority of participants had an undetectable viral load (n = 1375, 78.35%). Participants with pLLV had an increased rate of developing any NCD (aHR: 1.22, 95% CI: 1.02−1.47) compared to participants with an undetectable viral load. There was a statistically significant interaction between LLV and TNF‐α, CCL2/MCP‐1 and TNF‐RII in the association with any NCD. Conclusions: PLLV was significantly associated with NCDs and immune inflammation in this population. Aggressive management of LLV may positively impact NCDs in PLWH., INTRODUCTION Despite improved life expectancy with antiretroviral therapy (ART), people living with HIV (PLWH) have higher rates of non‐infectious comorbid diseases (NCDs) than do people living without HIV [1–5]. The [...]

: Introduction: Social network strategies, in which social networks are utilized to influence individuals or communities, are increasingly being used to deliver human immunodeficiency virus (HIV) interventions to key populations. We summarized and critically assessed existing research on the effectiveness of social network strategies in promoting HIV self‐testing (HIVST). Methods: Using search terms related to social network interventions and HIVST, we searched five databases for trials published between 1st January 2010 and 30th June 2023. Outcomes included uptake of HIV testing, HIV prevalence and linkage to antiretroviral therapy (ART) or HIV care. We used network meta‐analysis to assess the uptake of HIV testing through social network strategies compared with control methods. A pairwise meta‐analysis of studies with a comparison arm that reported outcomes was performed to assess relative risks (RR) and their corresponding 95% confidence intervals (CI). Results: Among the 4496 manuscripts identified, 39 studies fulfilled the inclusion criteria, including one quasi‐experimental study, 22 randomized controlled trials and 16 observational studies. Networks HIVST testing was organized by peers (distributed to known peers, 15 studies), partners (distributed to their sexual partners, 16 studies) and peer educators (distributed to unknown peers, 8 studies). Among social networks, simulating the possibilities of ranking position, peer distribution had the highest uptake of HIV testing (84% probability), followed by partner distribution (80% probability) and peer educator distribution (74% probability). Pairwise meta‐analysis showed that peer distribution (RR 2.29, 95% CI 1.54−3.39, 5 studies) and partner distribution (RR 1.76, 95% CI 1.50−2.07, 10 studies) also increased the probability of detecting HIV reactivity during testing within the key population when compared to the control. Discussion: All of the three social network distribution strategies enhanced the uptake of HIV testing compared to standard facility‐based testing. Linkage to ART or HIV care remained comparable to facility‐based testing across the three HIVST distribution strategies. Conclusions: Network‐based HIVST distribution is considered effective in augmenting HIV testing rates and reaching marginalized populations compared to facility‐based testing. These strategies can be integrated with the existing HIV care services, to fill the testing gap among key populations globally. PROSPERO Number: CRD42022361782, INTRODUCTION Human immunodeficiency virus (HIV) testing is considered as a significant stage of the HIV care continuum and prevention services [1]. Knowledge of HIV status contributes to timely treatment and [...]

: Introduction: Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP). Methods: We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase‐3 trial clinical trial in South Africa (study dates: January 2017–February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment‐emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment‐emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI). Results: Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0−3.4), −0.5 mmHg (95% CI: −2.2 to 1.7) and −2.1 mmHg (95% CI: −3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4–22.9), 15.4% (95% CI: 11.0–19.9) and 13.3% (95% CI: 8.9–17.6) of participants developed treatment‐emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment‐emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present. Conclusions: In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment‐emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care. Clinical Trial Number: NCT03122262, INTRODUCTION The evolution of antiretroviral therapy in the last decade has seen the introduction of integrase‐strand transfer inhibitors (INSTIs) in fixed‐dose combinations with tenofovir prodrugs, either tenofovir disoproxil fumarate (TDF) [...]

: Introduction: Evidence‐based intervention strategies to improve adherence among individuals living with chronic conditions are critical in ensuring better outcomes. In this systematic review, we assessed the impact of interventions that aimed to promote adherence to treatment for chronic conditions. Methods: We systematically searched PubMed, Web of Science, Scopus, Google Scholar and CINAHL databases to identify relevant studies published between the years 2000 and 2023 and used the QUIPS assessment tool to assess the quality and risk of bias of each study. We extracted data from eligible studies for study characteristics and description of interventions for the study populations of interest. Results: Of the 32,698 total studies/records screened, 2814 were eligible for abstract screening and of those, 497 were eligible for full‐text screening. A total of 82 studies were subsequently included, describing a total of 58,043 patients. Of the total included studies, 58 (70.7%) were related to antiretroviral therapy for HIV, 6 (7.3%) were anti‐hypertensive medication‐related, 12 (14.6%) were anti‐diabetic medication‐related and 6 (7.3%) focused on medication for more than one condition. A total of 54/82 (65.9%) reported improved adherence based on the described study outcomes, 13/82 (15.9%) did not have clear results or defined outcomes, while 15/82 (18.3%) reported no significant difference between studied groups. The 82 publications described 98 unique interventions (some studies described more than one intervention). Among these intervention strategies, 13 (13.3%) were multifaceted (4/13 [30.8%] multi‐component health services‐ and community‐based programmes, 6/13 [46.2%] included individual plus group counselling and 3/13 [23.1%] included SMS or alarm reminders plus individual counselling). Discussion: The interventions described in this review ranged from adherence counselling to more complex interventions such as mobile health (mhealth) interventions. Combined interventions comprised of different components may be more effective than using a single component in isolation. However, the complexity involved in designing and implementing combined interventions often complicates the practicalities of such interventions. Conclusions: There is substantial evidence that community‐ and home‐based interventions, digital health interventions and adherence counselling interventions can improve adherence to medication for chronic conditions. Future research should answer if existing interventions can be used to develop less complicated multifaceted adherence intervention strategies., INTRODUCTION Patients on treatment for chronic conditions face multiple barriers to adherence, and no single intervention is deemed sufficient to ensure that high levels of adherence to treatment are maintained [...]

: Introduction: To achieve epidemic control of infectious diseases, engaging higher‐burden populations with accessible diagnostic services is critical. HIV self‐testing (HIVST) is a promising option. Methods: We implemented an online HIVST programme for key populations across India. Eligible clients were 18 years or older, self‐reported a negative or unknown HIV status and reported not taking antiretroviral therapy. Clients who reported a prior HIV diagnosis were not eligible to receive an HIVST kit. HIVST clients received kits via courier or in person at pre‐determined pick‐up points supported by trained counselling staff. Virtual counsellors engaged clients online and by phone and offered support to register, access, and complete HIVST free of cost. Virtual counsellors supported clients to report results and engage with follow‐up services. Follow‐up included linking clients with a positive result to confirmatory testing and HIV care services. We assessed programmatic data across HIV continuum outcomes and conducted a qualitative evaluation through interviews with purposively sampled clients. Results: Between 30 June 2021 and 30 September 2022, 5324 clients ordered an HIVST kit (76% men, 13% women, 7% transgender people, 4% unknown gender). Of the 4282 clients reporting results (94% of those who received a kit), 6% screened positive, among whom 72% (n = 184) completed confirmatory testing. Themes from 41 client interviews included satisfaction about the convenience and privacy of services and the discreet nature of kit delivery. Respondents were drawn to the convenience of HIVST and appreciated gaining courage and comfort throughout the process from virtual counsellor support. For respondents who screened positive, challenges to care linkage included fearing judgemental questions from public providers and wanting more time before starting treatment. Clients shared concerns about kit accuracy and suggested that instructional materials be provided with more diverse language options. Conclusions: Web‐based HIVST services with tailored support appeared to facilitate HIV service access and engagement of harder‐to‐reach populations across India. Assistance from a community‐oriented counsellor proved important to overcome literacy barriers and mistrust in order to support the HIVST process and service linkage. Learnings can inform global efforts to improve the critical step of diagnosis in achieving epidemic control for HIV and other infectious diseases., INTRODUCTION Globally, infectious disease programmes have ambitious targets to achieve epidemic control or elimination. UNAIDS has established 95‐95‐95 targets for HIV wherein 95% of people living with HIV (PLHIV) are [...]

: Introduction: South African men face a substantial burden of HIV and are less likely to test for HIV and initiate antiretroviral therapy if tested positive and more likely to die from AIDS‐related causes than women. In addition to condoms and circumcision, guidelines provide for the use of daily oral pre‐exposure prophylaxis (PrEP) as an HIV prevention intervention for any men who recognize their need and request PrEP. However, heterosexual men have not been a focus of PrEP programmes, and since its introduction, there is limited literature on PrEP use among men in South Africa. This study explores the experiences, motivators and barriers to oral PrEP use among heterosexual men accessing primary healthcare services in South Africa. Methods: This study forms part of a mixed‐methods implementation science study aimed at generating evidence for oral PrEP introduction and conducted in primary healthcare clinics in South Africa since 2018. Men aged ≥15 years who initiated oral PrEP and enrolled in a parent cohort study were purposefully invited to participate in an in‐depth interview (IDI). Between March 2020 and May 2022, 30 men participated in IDIs exploring their motivators for PrEP use, and experiences with accessing health services. Interviews were audio recorded, transcribed and analysed thematically. Results: The final analysis included 28 heterosexual men (18–56 years old). Motivations to initiate PrEP included fear of acquiring HIV, self‐perceived vulnerability to HIV and mistrust in relationships; health systems factors which motivated PrEP use included the influence of healthcare providers, educational materials and mobile services. Perceived reduction in HIV vulnerability and changing proximity to partners were reasons for PrEP discontinuation. Side effects, daily‐pill burden and stigma were noted as challenges to PrEP use. Health system barriers to PrEP use included limited PrEP availability, school and work demands, and inconsistent mobile clinic schedules. Conclusions: Our study reports on the experiences of heterosexual men accessing oral PrEP in real‐world settings and contributes to the limited literature among this population. We highlight multiple levels which could be strengthened to improve men's PrEP use, including individual support, education among partners and communities, and addressing health system barriers to access., INTRODUCTION South Africa had an estimated 7.6 million people living with HIV in 2022, of whom 2.6 million (34%) are men aged ≥15 years [1]. Despite the implementation of the [...]

: Introduction: Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low‐ and middle‐income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. Methods: We conducted a cross‐sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA‐Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration‐controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. Results: Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45−56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1−8.4) and 28.4% (95% CI 26.5−30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10−2.40), overweight/obesity (OR = 2.50, 95% CI 1.69−3.75), T2DM (OR 2.26, 95% CI 1.46−3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46−6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti‐HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29−5.51), T2DM (OR 2.06, 95% CI 1.47−2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27−2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31−2.16). Conclusions: Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings., INTRODUCTION With the expanded coverage of antiretroviral treatment (ART), AIDS‐related mortality among persons living with HIV (PLHIV) has substantially decreased, resulting in a growing burden of non‐AIDS comorbidities, including liver [...]

: Introduction: In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception. Methods: We analysed data from people living with HIV (aged 15–49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan–Meier curves and proportional‐hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum. Results: Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25–27%) had disengaged from care by 1 year and 34% (95% CI 33–36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70–2.60), restarted (C: aHR 3.32, 95% CI 2.70–4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12–2.74) had increased hazards of postpartum disengagement compared to those on ART (A). Conclusions: There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care., INTRODUCTION Although antiretroviral therapy (ART) is recommended for all people living with HIV (PLHIV), major challenges persist with engagement in care [1, 2]. For pregnant PLHIV, the benefits of lifelong [...]

Background While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. Methods and findings For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged [greater than or equal to]15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with [greater than or equal to]12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. Conclusions In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality., Author(s): Ellen Brazier 1,2,*, Olga Tymejczyk 1, Kara Wools-Kaloustian 3, Awachana Jiamsakul 4, Marco Tulio Luque Torres 5, Jennifer S. Lee 6, Lisa Abuogi 7, Vohith Khol 8, Fernando Mejía [...]

HIV-1 persists in a latent reservoir in resting [CD4.sup.+] T cells despite antiretroviral therapy (ART). The reservoir decays slowly over the first 7 years of ART ([t.sub.1/2] = 44 months). However, whether decay continues with long-term ART is unclear. Recent integration site studies indicate gradual selection against inducible, intact proviruses, raising speculation that decades of ART might allow treatment interruption without viral rebound. Therefore, we measured the reservoir in 42 people on long-term ART (mean 22 years) using a quantitative viral outgrowth assay. After 7 years of ART, there was no long-term decrease in the frequency of inducible, replication-competent provi ruses but rather an increase with an estimated doubling time of 23 years. Another reservoir assay, the intact proviral DNA assay, confirmed that reservoir decay with [t.sub.1/2] of 44 months did not continue with long-term ART. The lack of decay reflected proliferation of infected cells. Most inducible, replication-competent viruses (79.8%) had env sequences identical to those of other isolates from the same sample. Thus, although integration site analysis indicates changes in reservoir composition, the proliferation of CD4* T cells counteracts decay, maintaining the frequency of inducible, replication-competent proviruses at roughly constant levels over the long term. These results reinforce the need for lifelong ART., Introduction Antiretroviral therapy (ART) blocks HIV-1 replication, reducing plasma virus levels to below the detection limit of clinical assays (1-3). ART prevents disease progression but does not eliminate the latent [...]

The use of antiretroviral therapy (ART) has shown markedly decreased sickness and death rates in persons living with HIV (PLWH) (1-3). Meanwhile, the emergence of antimicrobial drug resistance in HIV-1 [...]

Introduction: We conducted a cohort study to understand patterns of anti-retroviral therapy (ART) adherence during pregnancy postpartum and non-pregnancy follow-up among women initiating ART in public clinics offering Option B+ in rura Uganda and urban South Africa. Methods: We collected survey data, continuously monitored ART adherence (Wisepill), HIV-RNA and pregnancy tests at zero, six and twelve months from women initiating ART in Uganda and South Africa, 2015 to 2017. The primary predictor of interest was follow-up time categorized as pregnant (pregnancy diagnosis to pregnancy end), postpartum (pregnancy end to study exit) or non-pregnancy-related (neither pregnant nor postpartum). Fractional regression models included demographics and socio-behavioural factors informed by the Behavioral Model for Vulnerable Populations. We evaluated HIV-RNA at 12 months by ever- versus never-pregnant status. Results: In Uganda, 247 women contributed 676, 900 and 1274 months of pregnancy, postpartum and non-pregnancy-related follow-up. Median ART adherence was consistently [greater than or equal to]90%: pregnancy, 94% (interquartile range [IQR] 78,98); postpartum, 90% (IQR 70,97) and non-pregnancy 90% (IQR 80,98). Poorer adherence was associated with younger age (0.98% [95% CI 0.33%, 1.62%] average increase per year of age) and higher CD4 cell count (1.01% [0.08%, 1.94%] average decrease per 50 cells/[mm.sup.3]). HIV-RNA was suppressed among 91% (N = 135) ever-pregnant and 86% (N = 85) never-pregnant women. In South Africa, 190 women contributed 259, 624 and 1247 months of pregnancy, postpartum and non-pregnancy-related follow-up. Median adherence was low during pregnancy, 74% (IQR 31,96); postpartum, 40% (IQR 4,65) and non-pregnancy 77% (IQR 47,92). Poorer adherence was associated with postpartum status (22.3% [95%CI 8.6%, 35.4%] average decrease compared to non-pregnancy-related follow-up) and less emotional support (1.4% [0.22%, 2.58%] average increase per unit increase). HIV-RNA was suppressed among 57% (N = 47) ever-pregnant and 86% (N = 93) never-pregnant women. Conclusions: Women in rural Uganda maintained high adherence with 91% of ever-pregnant and 86% of never-pregnant women suppressing HIV-RNA at 12 months. Women in urban South Africa struggled with adherence, particularly during postpartum follow-up with median adherence of 40% and 57% of women with HIV-RNA suppression at one year, suggesting a crisis for postpartum women with HIV in South Africa. Findings suggest that effective interventions should promote emotiona support. Keywords: adherence; ARV; Cohort studies; gender; Africa < Region; women; HIV; adherence; ARV; cohort studies; gender; Africa < Region; women; HIV, 1 | INTRODUCTION In 2013, the WHO updated guidelines for prevention of mother to child transmission of HIV (PMTCT) to recommend antiretroviral treatment (ART) for pregnant or breastfeeding women living [...]

Introduction: The World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults ([greater than or equal to]15 years of age) starting ART in Southern Africa. Methods: We analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count 1000 HIV-RNA copies/mL) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex. Results: Among 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01). Conclusions: CD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa. Keywords: CD4 lymphocyte count; viral load; Africa; Southern; antiretroviral therapy; highly active; Cohort studies; HIV infections, 1 | INTRODUCTION The World Health Organization (WHO) has recommended immediate initiation of antiretroviral therapy (ART) for all people living with HIV since 2015, regardless of CD4 cell count or [...]

Introduction: Efficacious antiretroviral treatment (ART) enables people to live long and healthy lives with HIV but young people are dying from AIDS-related causes more than ever before. Qualitative evidence suggest that various forms of HIV-related discrimination and resulting shame act as profound barriers to young people's engagement with HIV services. However, the impact of these risks on adolescent retention in HIV care has not been quantified. This study has two aims: (1) to examine whether and how different types of discrimination compromise retention in care among adolescents living with HIV in South Africa; and (2) to test whether internalized stigma mediates these relationships. Methods: Between 2014 and 2017, adolescents living with HIV (aged 10 to 19) from 53 health facilities in the Eastern Cape, South Africa, were interviewed at baseline (n = 1059) and 18-month follow-up (n = 979, 92.4%), with responses linked to medical records. Data were analysed through multiple regression and mediation models. Results: About 37.9% of adolescents reported full retention in care over the 2-year period, which was associated with reduced odds of viral failure (OR: 0.371; 95% CI: .224, .614). At baseline, 6.9% of adolescents reported discrimination due to their HIV status; 14.9% reported discrimination due to HIV in their families and 19.1% reported discrimination in healthcare settings. Healthcare discrimination was associated with reduced retention in care both directly (effect: -0.120; CI: -0.190, -0.049) and indirectly through heightened internalized stigma (effect: 0.329; 95% CI: 0.129, 0.531). Discrimination due to family HIV was associated with reduced retention in care both directly (effect: -0.074, CI: -0.146, -0.002) and indirectly through heightened internalized stigma (effect: 0.816, CI: 0.494, 1.140). Discrimination due to adolescent HIV was associated with reduced retention in care only indirectly, through increased internalized stigma (effect: 0.408; CI: 0.102, 0.715). Conclusions: Less than half of adolescents reported 2-year retention in HIV care. Multiple forms of discrimination and the resultant internalized stigma contributed to this problem. More intervention research is urgently needed to design and test adolescent-centred interventions so that young people living with HIV can live long and healthy lives in the era of efficacious anti-retroviral treatment. Keywords: HIV; stigma; discrimination; adolescent; retention; adherence, 1 | INTRODUCTION There are 1.8 million adolescents living with HIV globally, of whom 1.5 million (85%) are in Sub-Saharan Africa [1]. At a time when efficacious antiretroviral treatment (ART) [...]

Introduction: In South Africa, an estimated 4.6 million people were accessing antiretroviral therapy (ART) in 2018. As universal Test and Treat is implemented, these numbers will continue to increase. Given the need for lifelong care for millions of individuals, differentiated service delivery models for ART services such as adherence clubs (ACs) for stable patients are required. In this study we describe long-term virologic outcomes of patients who have ever entered ACs in Khayelitsha, Cape Town. Methods: We included adult patients enrolled in ACs in Khayelitsha between January 2011 and December 2016 with a recorded viral load (VL) before enrolment. Risk factors for an elevated VL (VL >1000 copies/mL) and confirmed virologic failure (two consecutive VLs >1000 copies/mL one year apart) were estimated using Cox proportional hazards models. VL completeness over time was assessed. Results: Overall, 8058 patients were included in the analysis, contributing 16,047 person-years of follow-up from AC entry (median follow-up time 1.7 years, interquartile range [IQR]:0.9 to 2.9). At AC entry 74% were female, 46% were aged between 35 and 44 years, and the median duration on ART was 4.8 years (IQR: 3.0 to 7.2). Among patients virologically suppressed at AC entry (n = 8058), 7136 (89%) had a subsequent VL test, of which 441 (6%) experienced an elevated VL (median time from AC entry 363 days, IQR: 170 to 728). Older age (adjusted hazard ratio [aHR] 0.64, 95% confidence interva [CI] 0.46 to 0.88), more recent year of AC entry (aHR 0.76, 95% CI 0.68 to 0.84) and higher CD4 count (aHR 0.67, 95% CI 0.54 to 0.84) were protective against experiencing an elevated VL. Among patients with an elevated VL, 52% (150/291) with a repeat VL test subsequently experienced confirmed virologic failure in a median time of 112 days (IQR: 56 to 168). Frequency of VL testing was constant over time (82 to 85%), with over 90% of patients remaining virologically suppressed. Conclusions: This study demonstrates low prevalence of elevated VLs and confirmed virologic failure among patients who entered ACs. Although ACs were expanded rapidly most patients were well monitored and remained stable, supporting the continued rollout of this model. Keywords: HIV; antiretroviral therapy; antiretroviral treatment; adherence clubs; virologic failure; elevated viral load; virologic responses; Sub-Saharan Africa; differentiated service delivery models; viral load monitoring, 1 | INTRODUCTION In 2018, there were approximately 37.9 million people living with HIV (PLHIV), with nearly 23.3 million PLHIV accessing antiretroviral therapy (ART) [1]. HIV prevalence in South Africa [...]

Introduction: Despite improved treatment and access to care, adolescent AIDS deaths are decreasing more slowly than in any other age group. There is lack of longitudinal data around adolescent adherence and the dynamics of viraemia over time. We aimed to describe patterns of detectable viral load (VL) in a cohort of adolescents attending an ARV clinic in Cape Town, South Africa. Methods: We conducted a retrospective cohort study of all patients on antiretroviral therapy aged 10 to 19 years. Participants were included if they underwent at least two VL measurements and remained in care at the Groote Schuur Hospita HIV Clinic for at least 24 months between 2002 and 2016. The primary outcome was two consecutive HIV VL >100 copies/mL, in line with the lower limit of detection of assays in use over the follow-up period. Results and discussion: Of the 482 screened participants, 327 met inclusion criteria. Most participants had perinatally acquired HIV (n = 314; 96%), and 170 (52%) were males. Overall, there were 203 episodes of confirmed detectable VL involving 159 (49% (95% CI 43% to 54%)) participants during the follow-up period. Six participants had genotyped resistance to protease inhibitors. Four of these never suppressed, while two suppressed on salvage regimens. Total follow-up time was 1723 person years (PY), of which 880 (51%) were contributed by the 159 participants who experienced detectable VL. Overal time with detectable VL was 370 PY. This comprised 22% of total follow-up time, and 42% of the follow-up time contributed by those who experienced detectable VL. The rate of detectable VL was 11.8 (95% CI 10.3 to 13.5) episodes per 100 PY. The risk increased by 24% for each year of increasing age (Relative Risk 1.24 (95% CI 1.17 to 1.31); p < 0.0001). There was no sex difference with respect to duration (p = 0.4), prevalence (p = 0.46) and rate (p = 0.608) of detectable VL. Conclusions: Clinicians need to be alert to the high prevalence of detectable VL during adolescence so as to pre-empt it and act swiftly once it is diagnosed. This study helps to highlight the risk of detectable VL that is associated with increase in age as well the high proportion of time that poorly adherent adolescents spend in this state. Keywords: adolescents; adherence; viral suppression; ARV; Sub-Saharan Africa, 1 | INTRODUCTION AIDS-related deaths in adolescents are decreasing much slower than in all other age groups despite improved treatment and access to care [1,2]. HIV/AIDS is one of the [...]

Introduction: Real-time electronic adherence monitoring (EAM) systems could inform on-going risk assessment for HIV viraemia and be used to personalize viral load testing schedules. We evaluated the potential of real-time EAM (transferred via cellular signal) and standard EAM (downloaded via USB cable) in rural Uganda to inform individually differentiated viral load testing strategies by applying machine learning approaches. Methods: We evaluated an observational cohort of persons living with HIV and treated with antiretroviral therapy (ART) who were monitored longitudinally with standard EAM from 2005 to 2011 and real-time EAM from 2011 to 2015. Super learner, an ensemble machine learning method, was used to develop a tool for targeting viral load testing to detect viraemia (>1000 copies/ml) based on clinical (CD4 count, ART regimen), viral load and demographic data, together with EAM-based adherence. Using sample-splitting (cross-validation), we evaluated area under the receiver operating characteristic curve (cvAUC), potential for EAM data to selectively defer viral load tests while minimizing delays in viraemia detection, and performance compared to WHO-recommended testing schedules. Results: In total, 443 persons (1801 person-years) and 485 persons (930 person-years) contributed to standard and real-time EAM analyses respectively. In the 2011 to 2015 dataset, addition of real-time EAM (cvAUC: 0.88; 95% CI: 0.83, 0.93) significantly improved prediction compared to clinical/demographic data alone (cvAUC: 0.78; 95% CI: 0.72, 0.86; p = 0.03). In the 2005 to 2011 dataset, addition of standard EAM (cvAUC: 0.77; 95% CI: 0.72, 0.81) did not significantly improve prediction compared to clinical/demographic data alone (cvAUC: 0.70; 95% CI: 0.64, 0.76; p = 0.08). A hypothetical testing strategy using real-time EAM to guide deferral of viral load tests would have reduced the number of tests by 32% while detecting 87% of viraemia cases without delay. By comparison, the WHO-recommended testing schedule would have reduced the number of tests by 69%, but resulted in delayed detection of viraemia a mean of 74 days for 84% of individuals with viraemia. Similar rules derived from standard EAM also resulted in potential testing frequency reductions. Conclusions: Our machine learning approach demonstrates potential for combining EAM data with other clinical measures to develop a selective testing rule that reduces number of viral load tests ordered, while still identifying those at highest risk for viraemia. Keywords: adherence; machine learning; real-time adherence monitoring; viral load monitoring; virologic failure; viraemia, 1 | INTRODUCTION World Health Organization (WHO) guidelines now recommend antiretroviral treatment (ART) for all persons living with HIV, the majority of whom live in resource-limited settings [1,2]. International consensus [...]

Introduction: Lifelong antiretroviral therapy (ART) improves health outcomes for HIV-positive individuals, but is jeopardized by irregular clinic attendance and hence poor adherence. Loss to follow-up (LTFU) is typically defined retrospectively but this may lead to biased inferences. We assessed incidence of and factors associated with LTFU, prospectively and accounting for recurrent LTFU episodes, in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) of HIV-positive persons in rura Tanzania. Methods: We included adults ([greater than or equal to]15 years) enrolled in 2005 to 2016, regardless of ART status, with follow-up through Apri 2017. LTFU was defined as >60 days late for a scheduled appointment. Participants could experience multiple LTFU episodes. We performed analyses based on the first (prospective) and last (retrospective) events observed during follow-up, and accounting for recurrent LTFU episodes. Time to LTFU was estimated using cumulative incidence functions. We assessed factors associated with LTFU using cause-specific proportional hazards, marginal means/rates, and Prentice, Williams and Peterson models. Results: Among 8087 participants (65% female, 60% aged [greater than or equal to]35 years, 42% WHO stage 3/4, and 47% CD4 count Conclusions: LTFU episodes were common and prompt tracing efforts are urgently needed. We identified socio-demographic and clinical characteristics associated with LTFU that can be used to target tracing efforts and to help inform the design of appropriate interventions. Incidence of and risk factors for LTFU differed based on the LTFU definition applied, highlighting the importance of appropriately accounting for recurrent LTFU episodes. We recommend using a prospective definition of LTFU combined with recurrent event analyses in cohorts where repeated interruptions in care are common. Keywords: lost to follow-up; recurrent events; HIV infections; Tanzania; cohort; proportional hazards models, 1 | INTRODUCTION Lifelong antiretroviral therapy (ART) is crucial to optimize health outcomes for people living with HIV [1]. Retention in care is a critical component to reaching the second [...]

Introduction: The Treat-All policy--antiretroviral therapy (ART) initiation irrespective of CD4 cell criteria--increases access to treatment. Many ART programmes, however, reported increasing attrition and viral failure during treatment expansion, questioning the programmatic feasibility of Treat-All in resource-limited settings. We aimed to describe and compare programmatic outcomes between Treat-All and standard of care (SOC) in the public sectors of Eswatini. Methods: This is a prospective cohort study of [greater than or equal to]16-year-old HIV-positive patients initiated on first-line ART under Treat-Al and SOC in 18 health facilities of the Shiselweni region, from October 2014 to March 2016. SOC followed the CD4 350 and 500 cells/[mm.sup.3] treatment eligibility thresholds. Kaplan-Meier estimates were used to describe crude programmatic outcomes. Multivariate flexible parametric survival models were built to assess associations of time from ART initiation with the composite unfavourable outcome of all-cause attrition and viral failure. Results: Of the 3170 patients, 1888 (59.6%) initiated ART under Treat-All at a median CD4 cell count of 329 (IQR 168 to 488) cells/[mm.sup.3] compared with 292 (IQR 161 to 430) (p < 0.001) under SOC. Although crude programme retention at 36 months tended to be lower under Treat-All (71%) than SOC (75%) (p = 0.002), it was similar in covariate-adjusted analysis (adjusted hazard ratio [aHR] 1.06, 95% CI 0.91 to 1.23). The hazard of viral suppression was higher for Treat-All (aHR 1.12, 95% CI 1.01 to 1.23), while the hazard of viral failure was comparable (Treat-All: aHR 0.89, 95% CI 0.53 to 1.49). Among patients with advanced HIV disease (n = 1080), those under Treat-All (aHR 1.13, 95% CI 0.88 to 1.44) had a similar risk of an composite unfavourable outcome to SOC. Factors increasing the risk of the composite unfavourable outcome under both interventions were aged 16 to 24 years, being unmarried, anaemia, ART initiation on the same day as HIV care enrolment and CD4 [less than or equal to] 100 cells/[mm.sup.3]. Under Treat-All only, the risk of the unfavourable outcome was higher for pregnant women, WHO III/IV clinical stage and elevated creatinine. Conclusions: Compared to SOC, Treat-All resulted in comparable retention, improved viral suppression and comparable composite outcomes of retention without viral failure. Keywords: treat all; retention; viral failure; Swaziland; Eswatini; HIV, 1 | INTRODUCTION The World Health Organization (WHO) recommends antiretroviral therapy (ART) initiation at the time of HIV diagnosis irrespective of clinical and immunological criteria, aiming at improving patient-level outcomes [...]

Introduction: Online, supervised, HIV self-testing has potential to reach men who have sex with men (MSM) and transgender women (TGW) who never tested before and who had high HIV-positive yield. We studied linkages to HIV confirmatory test and antiretroviral therapy (ART) initiation among Thai MSM and TGW who chose online and/or offline platforms for HIV testing and factors associated with unsuccessful linkages. Methods: MSM and TGW were enrolled from Bangkok Metropolitan Region and Pattaya during December 2015 to June 2017 and followed for 12 months. Participants could choose between: 1) offline HIV counselling and testing (Offline group), 2) online pre-test counselling and offline HIV testing (Mixed group) and 3) online counselling and online, supervised, HIV self-testing (Online group). Sociodemographic data, risk behaviour and social network use characteristics were collected by self-administered questionnaires. Linkages to HIV confirmatory testing and/or ART initiation were collected from participants who tested reactive/positive at baseline and during study follow-up. Modified Poisson regression models identified covariates for poor retention and unsuccessful ART initiation. Results: Of 465 MSM and 99 TGW, 200 self-selected the Offline group, 156 the Mixed group and 208 the Online group. The Online group demonstrated highest HIV prevalence (15.0% vs. 13.0% vs. 3.4%) and high HIV incidence (5.1 vs. 8.3 vs. 3.2 per 100 person-years), compared to the Offline and Mixed groups. Among 60 baseline HIV positive and 18 seroconversion participants, successful ART initiation in the Online group (52.8%) was lower than the Offline (84.8%) and Mixed groups (77.8%). Factors associated with unsuccessful ART initiation included choosing to be in the Online group (aRR 3.94, 95% CI 1.07 to 14.52), Conclusions: Online, supervised, HIV self-testing allowed more MSM and TGW to know their HIV status. However, linkages to confirmatory test and ART initiation once tested HIV-reactive are key challenges. Alternative options to bring HIV test confirmation, prevention and ART services to these individuals after HIV self-testing are needed. Keywords: online; HIV self-testing; link to care; men who have sex with men; transgender women, 1 | INTRODUCTION HIV testing uptake among key populations (KPs), in particularly men who have sex with men (MSM) and transgender women (TGW) in Thailand, has been low over the [...]