An overview of tenofovir and renal disease for the HIV-treating clinician

Tenofovir disoproxil fumarate (TDF, commonly termed ‘tenofovir’) is the antiretroviral most commonly implicated in antiretroviral-induced nephrotoxicity. As patients on successful antiretroviral therapy (ART) age, their risk for developing renal disease may increase in part because of ART itself, but more importantly, because of HIV-associated and non-HIVassociated comorbidity. Therefore, clinicians need an approach to managing renal disease in people on TDF. TDF as a cause of acute kidney injury (AKI) or chronic kidney disease (CKD) is uncommon, and clinicians should actively exclude other causes (Box 1). In TDF-associated AKI, TDF should be interrupted in all cases, and replaced, or ART interrupted altogether. Tenofovir disoproxil fumarate toxicity can present as AKI or CKD, and as a full or partial Fanconi’s syndrome. TDF has a small but definite negative impact on kidney function (up to a 10% decrease in glomerular filtration rate [GFR]). This occurs because of altered tubular function in those exposed to TDF for treatment and as pre-exposure prophylaxis. Renal function should be assessed using creatinine-based estimated GFR at the time of initiation of TDF, if ART is changed, at 1–3 months, and then ideally every 6–12 months if stable. Specific tests of tubular function are not routinely recommended; in the case of clinical concern, a spot protein or albumin: creatinine ratio is preferable, but in resource-limited settings, urine dipstick can be used. More frequent monitoring may be required in those with established CKD (estimated glomerular filtration rate [eGFR] < 50 mL/min/1.73 m2) or risk factors for kidney disease. The most common risk factors are comorbid hypertension, diabetes, HIV associated kidney disease, hepatitis B or C co-infection, and TDF in combination with a ritonavir-boosted protease inhibitor. Management of these comorbid conditions must be prioritised in this group. If baseline screening eGFR is < 50 mL/min/1.73 m2, abacavir (the preferred option), and dose-adjusted TDF (useful if concomitant hepatitis B), zidovudine or stavudine (d4T) remain alternatives to full-dose TDF. If there is a rapid decline in kidney function (eGFR drops by more than 25% and decreases to < 50 mL/min/1.73 m2 from of baseline function), or there is new onset or worsening of proteinuria or albuminuria, clinicians should review ART and other potentially nephrotoxic medications and comorbidity and conduct further testing if indicated. If kidney function does not improve after addressing reversible causes of renal failure, then referral to a nephrologist is appropriate. In the case of severe CKD, timeous referral for planning for renal replacement therapy is recommended. Tenofovir alafenamide, a prodrug of tenofovir, appears to have less renal toxicity and is likely to replace TDF in future

Profile of presentation of HIV-positive patients to an emergency department in Johannesburg, South Africa

BACKGROUND: Despite improved availability and better access to antiretroviral therapy (ART), approximately 36% of human immunodeficiency virus (HIV)-positive South Africans are still not virally suppressed. Objective: The aim of this study was to describe the patterns of presentation of HIV-positive patients to a major central hospital emergency department (ED). METHODS: In this prospectively designed study, consecutive HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) adult ED were enrolled between 07 July 2017 and 18 October 2018. RESULTS: A total of 1224 participants were enrolled. Human immunodeficiency virus was newly diagnosed in 212 (17.3%) patients, 761 (75.2%) were on ART, 245 (32.2%) reported ART non-adherence, 276 (22.5%) had bacterial pneumonia, 244 (19.9%) had tuberculosis (TB), 86 (7.0%) had gastroenteritis, 205 (16.7%) required intensive care unit admission, 381 (31.1%) were admitted for ≥ 7 days and 166 (13.6%) died. With regard to laboratory parameters, CD4 cell count was < 100 cell/mm3 in 527 (47.6%) patients, the viral load (VL) was > 1000 copies/mL in 619 (59.0%), haemoglobin was < 11 g/dL in 636 (56.3%), creatinine was > 120 μmol/L in 294 (29.3%), lactate was > 2 mmol/L in 470 (42.0%) and albumin was < 35 g/L in 633 (60.8%). CONCLUSION: Human immunodeficiency virus-positive patients presenting to the CMJAH ED demonstrated a high prevalence of opportunistic infections, required a prolonged hospital stay and had high mortality rates. There is a need to improve the quality of ART services and accessibility to care.http://www.sajhivmed.org.za/index.php/hivmeddm2022Critical Car

Predictors of prolonged hospital stay in HIV-positive patients presenting to the emergency department

BACKGROUND: Prolonged hospitalization places a significant burden on healthcare resources. Compared to the general population, hospital length of stay (LOS) is generally longer in HIV-positive patients. We identified predictors of prolonged hospital length of stay (LOS) in HIV-positive patients presenting to an emergency department (ED). METHODS: In this cross-sectional study, HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED were prospectively enrolled between 07 July 2017 and 18 October 2018. Data was subjected to univariate and multivariate logistic regression to determine parameters associated with a higher likelihood of prolonged hospital LOS, defined as ≥7 days. RESULTS: Among the 1224 participants that were enrolled, the median (IQR) LOS was 4.6 (2.6–8.2) days, while the mean (SD) LOS was 6.9 (8.2) days. On multivariate analysis of the data, hemoglobin 120 μmol/L (OR 1.85, p = 0.000), cryptococcal meningitis (OR 2.45, p = 0.015) and bacterial meningitis (OR 4.83, p = 0.002) were significantly associated with a higher likelihood of LOS ≥7 days, while bacterial pneumonia (OR 0.35, p = 0.000) and acute gastroenteritis (OR 0.40, p = 0.025) were significantly associated with a lower likelihood of LOS ≥7 days. CONCLUSION: Various clinical and laboratory parameters are useful in predicting prolonged hospitalization among HIV-positive patients presenting to the ED. These parameters may be useful in guiding clinical decision making and directing the allocation of resources.http://www.plosone.orgpm2022Critical Car

Predictors of in-hospital mortality among HIV-positive patients presenting with an acute illness to the emergency department

OBJECTIVES : Despite better access to antiretroviral therapy (ART) over recent years, HIV remains a major global cause of mortality. The present study aimed to identify predictors of in-hospital mortality among HIV-positive patients presenting to an emergency department (ED). METHODS : In this cross-sectional study, HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED between 07 July 2017 and 18 October 2018 were prospectively enrolled. Data were compared between participants who survived to hospital discharge and those who died. The data were further subjected to univariate and multivariate logistic regression analyses to determine variables that were associated with in-hospital mortality. RESULTS : Of a total of 1224 participants, the in-hospital mortality was 13.6% (n = 166). On multivariate analysis, respiratory rate > 20 breaths/min [odds ratio (OR) = 1.90, P = 0.012], creatinine > 120 μmol/L (OR = 1.97, P = 0.006), oxygen saturation 2 mmol/L (OR = 4.83, P = 0.000) and cryptococcal meningitis (OR = 6.78, P = 0.000) were significantly associated with in-hospital mortality. CONCLUSIONS : Routine clinical and laboratory parameters are useful predictors of in-hospital mortality in HIV-positive patients presenting to the ED with an acute illness. These parameters may be of value in guiding clinical decision-making, directing the appropriate use of resources and influencing patient disposition, and may also be useful in developing an outcome prediction tool.http://www.wileyonlinelibrary.com/journal/hivhj2022Critical Car

Southern African HIV Clinicians Society guidelines for harm reduction

We support public-health-focused interventions, as opposed to recovery-focused interventions. We support the decriminalisation of drug use as much as we oppose the criminalisation of sex work, mandatory HIV disclosure and policing of sexual preferences.Additional inputs received from Lize Weich, Tanya Venter, Johannes Hugo, Urvisha Bhoora, Magriet Spies, Rafaela Rigoni, Cara O’Conner, Julia Samuelson, Viriginia Macdonald, Michelle Rodolph, Shona Dalal, Nurain Tisaker and Shaheema Allie. Regional harm reduction case studies developed by Kunal Naik (PILS, Mauritius) and Bernice Apondi (VOCAL, Kenya). Inputs from the guideline development workshop held in August 2019 are also included. Participants of the workshop included: Leora Casey, Andrew Gray, Harry Hausler, Signe Rotberga, Muhangwi Mulaudzi, Lauren Jankelowitz, Annette Verster, Busisiwe Msimanga-Radebe, Nontsikelelo Mpulo, Zukiswa Ngobo, Mpho Maraisane, Rogerio Phili, Kgalabi Ngako, Maria Sibanyoni, Yolanda Ndimande, Valencia Malaza, Johannes Hugo, Urvisha Bhoora and Cara O’Conner. We extend our thanks to the external reviewers, including Julie Bruneau, Annette Verster, Kunal Naik, Nkereuwem William Ebiti and Ali Feizzadeh.http://www.sajhivmed.org.za/am2021Family MedicineImmunolog

Intervention strategies to improve adherence to treatment for selected chronic conditions in sub-Saharan Africa: a systematic review

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

Development and internal validation of the HIV In-hospital mortality prediction (HIV-IMP) risk score

BACKGROUND : Despite advances in availability and access to antiretroviral therapy (ART), HIV still ranks as a major cause of global mortality. Hence, the aim of this study was to develop and internally validate a risk score capable of accurately predicting in-hospital mortality in HIV-positive patients requiring hospital admission. METHODS : Consecutive HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult emergency department between 7 July 2017 and 18 October 2018 were prospectively enrolled. Multivariate logistic regression was used to determine parameters for inclusion in the final risk score. Discrimination and calibration were assessed by means of the area under the receiver operating curve (AUROC) and the Hosmer–Lemeshow goodness-of-fit test, respectively. Internal validation was conducted using the regular bootstrap technique. RESULTS : The overall in-hospital mortality rate was 13.6% (n = 166). Eight predictors were included in the final risk score: ART non-adherence or not yet on ART, Glasgow Coma Scale 20 breaths/min, oxygen saturation 120 μmol/L, lactate > 2 mmol/L and albumin < 35 g/L. After internal validation, the risk score maintained good discrimination [AUROC 0.83, 95% confidence interval (CI): 0.78–0.88] and calibration (Hosmer–Lemeshow χ2 = 2.26, p = 0.895). CONCLUSION : The HIV In-hospital Mortality Prediction (HIV-IMP) risk score has overall good discrimination and calibration and is relatively easy to use. Further studies should be aimed at externally validating the score in varying clinical settings.http://www.wileyonlinelibrary.com/journal/hivhj2022Critical Car

Southern African HIV Clinicians Society 2023 Guideline for post-exposure prophylaxis: Updated recommendations

No abstract available

Point-of-Care Tenofovir Urine Testing for the Prediction of Treatment Failure and Drug Resistance During Initial Treatment for Human Immunodeficiency Virus Type 1 (HIV-1) Infection

BACKGROUND: Viral rebound during antiretroviral treatment (ART) is most often driven by suboptimal adherence in the absence of drug resistance. We assessed the diagnostic performance of point-of-care (POC) tenofovir (TFV) detection in urine for the prediction of viral rebound and drug resistance during ART. METHODS: We performed a nested case-control study within the ADVANCE randomized clinical trial (NCT03122262) in Johannesburg, South Africa. Adults with human immunodeficiency virus (HIV) and newly initiating ART were randomized to receive either dolutegravir or efavirenz, tenofovir disoproxil fumarate or alafenamide, and emtricitabine. All participants with rebound ≥200 copies/mL between 24 and 96 weeks of follow-up were selected as cases and matched to controls with virological suppression <50 copies/mL. Rapid POC urine-TFV detection was performed retrospectively. RESULTS: We included 281 samples from 198 participants. Urine-TFV was detectable in 30.7% (70/228) of cases and in 100% (53/53) of controls. Undetectable urine-TFV predicted rebound with a sensitivity of 69% [95% confidence interval {CI}: 63-75] and specificity of 100% [93-100]. In cases with virological failure and sequencing data (n = 42), NRTI drug resistance was detected in 50% (10/20) of cases with detectable urine-TFV versus in 8.3% (2/24) of cases with undetectable urine-TFV. Detectable urine-TFV predicted NRTI resistance (odds ratio [OR] 10.4 [1.8-114.4] P = .005) with a sensitivity of 83% [52-98] and specificity of 69% [50-84]. CONCLUSIONS: POC objective adherence testing using a urine-TFV test predicted viral rebound with high specificity. In participants with rebound, urine-TFV testing predicted the selection of drug resistance. Objective adherence testing may be used to rapidly provide insight into adherence, suppression, and drug resistance during ART

Predictors of impaired pulmonary function in people living with HIV in an urban African setting

Background: Studies have associated HIV with an increased risk of obstructive lung disease (OLD). Objectives: We aimed to identify the predictive factors for impaired lung function in an urban, African, HIV-positive population. Method: A cross-sectional study was performed in Johannesburg, South Africa, from July 2016 to November 2017. A questionnaire was administered and pre- and post-bronchodilator spirometry conducted. The predictors investigated included age, sex, antiretroviral treatment (ART) duration, body mass index, history of tuberculosis (TB) or pneumonia, occupational exposure, environmental exposure, smoking and symptoms of OLD (cough, wheeze, mucus and dyspnoea). Impaired lung function was defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of < 0.70, or below the 20th percentile of normal. Results: The 98 ART-naïve participants (mean age = 34.0, standard deviation [s.d.] = 8.2), 85 participants on first-line ART (mean age = 36.9, s.d. = 6.6) and 189 participants on second-line ART (mean age = 43.5, s.d. = 7.9) were predominantly female (65.6%). Of the participants, 64 (17.2%) had impaired lung function and 308 had normal lung function. Linear regression identified age (β = -0.003, P < 0.01), male sex (β = -0.016, P = 0.03) and history of TB or pneumonia (β = -0.024, P < 0.01) as independent predictors of a lower FEV1/FVC ratio. Following logistic regression, only a history of TB or pneumonia (odds ratio = 2.58, 95% confidence interval = 1.47-4.52) was significantly related to impaired lung function (area under the receiver operating characteristic curve = 0.64). Conclusion: Our data show that a history of TB or pneumonia predicts impaired lung function. In order to improve timely access to spirometry, clinicians should be alert to the possibility of impaired lung function in people with a history of TB or pneumonia