Search

BackgroundLong-term retention of research participants in studies is challenging. In research in sub-Saharan Africa, phone calls are the most frequently used method to distantly engage with participants. ObjectiveWe aimed to get insight into the effectiveness of phone calls to retain contact with participants and evaluated determinants of reachability. MethodsA cross-sectional study was performed using the databases of two randomized controlled trials investigating different kinds of antiretroviral therapy in HIV-positive patients. One trial finished in 2018 (study 1), and the other finished in 2015 (study 2). A random sample size of 200 participants per study was obtained. There were up to 3 phone numbers available per participant collected during the studies. Participants received a maximum of 3 phone calls on every available number on different days and at different times. Voicemails were left, and emails sent wherever possible. We documented how many calls were answered, who answered, as well as after how many attempts participants were reached. To further increase our understanding of reachability, we conducted a short questionnaire assessing factors contributing to reachability. The study was approved by the Research Ethics Committee of the University of Witwatersrand, Johannesburg, South Africa (reference number M1811107). ResultsIn our sample size of n=200 per study, study 1, with a median time of 11 months since the last visit at the research site, had a response rate of 70.5% (141/200) participants while study 2, with a median duration of 55 months since the last visit, had a response rate of 50.0% (100/200; P

BackgroundSouth Africa provides free antiretroviral therapy for almost 5 million people living with HIV, but only 71% of the eligible people are on treatment, representing a shortfall in the care cascade, especially among men and youth. Many developing countries have expanded access to smartphones; success in health apps raises the possibility of improving this cascade. ObjectiveSmartLink is a health app for Android smartphones providing HIV-related laboratory results, information, support, and appointment reminders to engage and link patients to care. This study aimed to evaluate the ability of SmartLink to improve linkage to care for HIV-positive smartphone owners. MethodsThis study was a multisite randomized controlled trial in Johannesburg. The intervention arm received the app (along with referral to a treatment site) and the control arm received the standard of care (referral alone). Linkage to care was confirmed by an HIV-related blood test reported on the National Health Laboratory Service database between 2 weeks and 8 months after initiation. ResultsA total of 345 participants were recruited into the study; 64.9% (224/345) of the participants were female and 44.1% (152/345) were aged less than 30 years. In addition, 46.7% (161/345) were employed full time, 95.9% (331/345) had at least secondary school education, and 35.9% (124/345) were from Zimbabwe. Linkage to care between 2 weeks and 8 months was 48.6% (88/181) in the intervention arm versus 45.1% (74/164) in the control (P=.52) and increased to 64.1% (116/181) and 61.0% (100/164) (P=.55), respectively, after the initial 8-month period. Moreover, youth aged 18 to 30-years showed a statistically significant 20% increase in linkage to care for the intervention group. ConclusionsYouth aged less than 30 years have been historically difficult to reach with traditional interventions, and the SmartLink app provides a proof of concept that this population reacts to mobile health interventions that engage patients in HIV care. Trial RegistrationClinicalTrials.gov NCT02756949; https://clinicaltrials.gov/ct2/show/NCT02756949 (Archived by WebCite at http://www.webcitation.org/6z1GTJCNW)

: 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) [...]

Purpose of Review: This review assesses recent developments in community access to pre-exposure prophylaxis (PrEP) for HIV prevention in low-and middle-income countries (LMICs). It examines literature on differentiated service delivery (DSD) and alternative delivery modes for PrEP, focusing on the role of community pharmacies and novel pick-up points. Key considerations include barriers to access, potential benefits, and strategies for implementation. Recent Findings: Challenges to optimal HIV healthcare delivery persist globally, with LMICs facing greater barriers due to resource constraints and structural obstacles. Community pharmacies and novel pick-up points offer promising avenues to expand access to HIV medication, especially in hard-to-reach populations. However, operational complexities and regulatory frameworks present significant challenges. Recent initiatives, such as collaborative practice agreements and programmes by global health agencies, highlight efforts to integrate community pharmacies into HIV prevention and care delivery. Mobile health clinics and home delivery services have also shown promise in improving treatment coverage. Summary: Community pharmacies and novel pick-up points play a crucial role in enhancing access to HIV PrEP in LMICs. Despite challenges related to infrastructure, funding, and regulatory oversight, innovative strategies like DSD and mobile outreach offer opportunities to reach marginalized populations. Real-life examples from LMICs demonstrate the feasibility and effectiveness of leveraging community pharmacies for HIV treatment. However, addressing policy gaps, strengthening pharmacist training, and promoting patient-centred approaches are essential for scaling up access to PrEP. Collaboration between governments, health agencies, and local communities is key to realizing the full potential of community pharmacies in HIV prevention and care. [ABSTRACT FROM AUTHOR]

Aims: Dolutegravir increases serum creatinine by inhibiting its renal tubular secretion and elimination. We investigated determinants of early changes in serum creatinine in a southern African cohort starting first‐line dolutegravir‐based antiretroviral therapy (ART). Methods: We conducted a secondary analysis of data from participants in a randomized controlled trial of dolutegravir, emtricitabine and tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide fumarate (TAF) (ADVANCE, NCT03122262). We assessed clinical, pharmacokinetic and genetic factors associated with change in serum creatinine from baseline to Week 4 using linear regression models adjusted for age, sex, baseline serum creatinine, HIV‐1 RNA concentration, CD4 T‐cell count, total body weight and co‐trimoxazole use. Results: We included 689 participants, of whom 470 had pharmacokinetic data and 315 had genetic data. Mean change in serum creatinine was 11.3 (SD 9.9) μmol.L−1. Factors that were positively associated with change in serum creatinine at Week 4 were increased log dolutegravir area under the 24‐h concentration–time curve (change in creatinine coefficient [β] = 2.78 μmol.L−1 [95% confidence interval (CI) 0.54, 5.01]), TDF use (β = 2.30 [0.53, 4.06]), male sex (β = 5.20 [2.92, 7.48]), baseline serum creatinine (β = −0.22 [−0.31, −0.12]) and UGT1A1 rs929596 A→G polymorphism with a dominant model (β = −2.33 [−4.49, −0.17]). The latter did not withstand correction for multiple testing. Conclusions: Multiple clinical and pharmacokinetic factors were associated with early change in serum creatinine in individuals initiating dolutegravir‐based ART. UGT1A1 polymorphisms may play a role, but further research on genetic determinants is needed. [ABSTRACT FROM AUTHOR]

Rapid advances in the potency, safety, and availability of modern HIV antiretroviral therapy (ART) have yielded a near-normal life expectancy for most people living with HIV (PLWH). Ironically, considering the history of HIV/AIDS (initially called "slim disease" because of associated weight loss), the latest dilemma faced by many people starting HIV therapy is weight gain and obesity, particularly Black people, women, and those who commenced treatment with advanced immunodeficiency. We review the pathophysiology and implications of weight gain among PLWH on ART and discuss why this phenomenon was recognized only recently, despite the availability of effective therapy for nearly 30 years. We comprehensively explore the theories of the causes, from initial speculation that weight gain was simply a return to health for people recovering from wasting to comparative effects of newer regimens vs prior toxic agents, to direct effects of agents on mitochondrial function. We then discuss the implications of weight gain on modern ART, particularly concomitant effects on lipids, glucose metabolism, and inflammatory markers. Finally, we discuss intervention options for PLWH and obesity, from the limitations of switching ART regimens or specific agents within regimens, weight-gain mitigation strategies, and potential hope in access to emerging antiobesity agents, which are yet to be evaluated in this population. [ABSTRACT FROM AUTHOR]

Participants randomized to first-line tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG), tenofovir disoproxil fumarate (TDF)/FTC + DTG, or TDF/FTC/efavirenz (EFV) for 192 weeks were then switched to TDF/lamivudine (3TC)/DTG for 52 weeks. Participants switching either TAF/FTC + DTG or TDF/FTC/EFV to TDF/3TC/DTG showed statistically significant reductions in weight, low-density lipoprotein, triglycerides, glucose and glycated hemoglobin. [ABSTRACT FROM AUTHOR]

Introduction: Southern and Eastern Africa bear the brunt of the AIDS epidemic, and current prevention interventions remain inadequate. Antiretroviral-based pre-exposure prophylaxis (PrEP) is gaining momentum as an effective prevention intervention. Discussion: Discussions have been started on how this strategy could be employed in Africa such that the populations most in need can be reached urgently for the greatest impact. This requires the selection of specific risk groups and service environments in which PrEP can be distributed safely and cost effectively while being mindful of any ethical issues. Conclusions: Given the need for an integrated public health approach to this, a number of potential populations and opportunities for PrEP distribution exist and are discussed in this commentary. Keywords: PrEP; HIV; AIDS; South Africa., Introduction Southern and Eastern Africa bear the brunt of the AIDS epidemic. Three out of every four people in the world commenced on antiviral therapy live in this region. South [...]

Purpose of Review: The introduction of dolutegravir, an oral integrase inhibitor, within public health HIV programs has been a success, with excellent sustained viral load suppression, persistence, and safety. Initial concerns around integrase-inhibitors being implicated in safety concerns around immune reconstitution inflammatory syndromes (IRIS), neural tube defects, and weight gain, have been largely laid to rest, but new concerns about cardiovascular risk have arisen, including a link between hypertension and this antiretroviral class., Recent Findings: We review the pertinent studies here, and while we find both observational and randomized controlled study associations in some but not all studies, these are often confounded by associated weight gain and aging. In addition, definitions of hypertension, as well as measurement within the studies (such as cuff size), were not consistent within studies., Summary: Careful analysis will be needed, as with the weight-gain signal, before assigning causation, especially as plausible physiological mechanisms for this rise in blood pressure are unclear., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reducing doses of antiretroviral drugs, including stavudine (d4T), may lower toxicity, while preserving efficacy. There are substantial concerns about renal and bone toxicities of tenofovir disoproxil fumarate (TDF)., Setting: HIV-1-infected treatment-naive adults in India, South Africa, and Uganda., Methods: A phase-4, 96-week, randomized, double-blind, noninferiority trial compared d4T 20 mg twice daily and TDF, taken in combination with lamivudine (3TC) and efavirenz (EFV). The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies per milliliter at 48 weeks. Adverse events assessments included measures of bone density and body fat. The trial is registered on Clinicaltrials.gov (NCT02670772)., Results: Between 2012 and 2014, 536 participants were recruited per arm. At week 96, trial completion rates were 75.7% with d4T/3TC/EFV (n = 406) and 82.1% with TDF/3TC/EFV (n = 440, P = 0.011). Noncompletion was largely due to virological failure [6.2% (33) with d4T/3TC/EFV versus 5.4% (29) with TDF/3TC/EFV; P = 0.60]. For the primary endpoint, d4T/3TC/EFV was noninferior to TDF/3TC/EFV (79.3%, 425/536 versus 80.8% 433/536; difference = -1.49%, 95% CI: -6.3 to 3.3; P < 0.001). Drug-related adverse event discontinuations were higher with d4T (6.7%, 36), than TDF (1.1%, 6; P < 0.001). Lipodystrophy was more common with d4T (5.6%, 30) than TDF (0.2%, 1; P < 0.001). Creatinine clearance increased in both arms, by 18.1 mL/min in the d4T arm and 14.2 mL/min with TDF (P = 0.03). Hip bone density measures, however, showed greater loss with TDF., Conclusions: Low-dose d4T combined with 3TC/EFV demonstrated noninferior virological efficacy compared with TDF/3TC/EFV, but mitochondrial toxicity remained high. Little renal toxicity occurred in either arm. Implications of bone mineral density changes with TDF warrant investigation.

Background: The World Health Organization recommends that antiretroviral therapy (ART) programs in resource-limited settings develop third-line ART policies. South Africa developed a national third-line ART program for patients who have failed both first-line non-nucleoside reverse transcriptase inhibitor-based ART and second-line protease inhibitor (PI)-based ART. We report on this program., Methods: Third-line ART in South Africa is accessed through a national committee that assesses eligibility and makes individual regimen recommendations. Criteria for third-line include the following: ≥1 year on PI-based ART with virologic failure, despite adherence optimization, and genotypic antiretroviral resistance test showing PI resistance. We describe baseline characteristics and resistance patterns of this cohort and present longitudinal data on virological suppression rates., Results: Between August 2013 and July 2014, 144 patients were approved for third-line ART. Median age was 41 years [interquartile range (IQR): 19-47]; 60% were women (N = 85). Median CD4 count and viral load were 172 (IQR: 128-351) and 14,759 (IQR: 314-90,378), respectively. About 2.8% started PI-based ART before 2004; 11.1% from 2004 to 2007; 31.3% from 2008 to 2011; and 6.3% from 2012 to 2014 (48.6% unknown start date). Of the 144 patients, 97% and 98% had resistance to lopinavir and atazanavir, respectively; 57% had resistance to darunavir. All were initiated on a regimen containing darunavir, with raltegravir in 101, and etravirine in 33. Among those with at least 1 viral load at least 6 months after third-line approval (n = 118), a large proportion (83%, n = 98) suppressed to <1000 copies per milliliter, and 79% (n = 93) to <400 copies per milliliter., Conclusion: A high proportion of third-line patients with follow-up viral loads are virologically suppressed.