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Background: Tuberculosis (TB) preventive therapy (TPT) reduces the risk of TB disease in people with human immunodeficiency virus (HIV), yet uptake has been suboptimal in many countries. We assessed whether QuantiFERON Gold In-Tube (QGIT) during routine HIV care increased TB infection (TBI) testing and TPT prescriptions., Methods: This parallel-arm, 1:1 cluster-randomized controlled trial compared the standard-of-care tuberculin skin test to QGIT in South Africa. We enrolled consenting, TPT-eligible adults diagnosed with HIV ≤30 days prior and used intention-to-treat analyses for the outcomes: proportion of patients with documented TBI results, proportion with documented TPT, and time from enrollment to outcomes., Findings: We enrolled 2232 patients across 14 clinics from November 2014 to May 2017 (58% in intervention clinics). At 24 months of follow-up, more participants in intervention clinics had TBI results (69% vs 2%, P < .001) and TPT prescriptions (45% vs 30%, P = .13) than control clinics. Controlling for baseline covariates, intervention clinics had 60% (95% confidence interval, 51-68; P < .001) more participants with TBI results and 12% (95% confidence interval, -6 to 31; P = .18) more with TPT prescriptions. Among participants with results, those in intervention clinics received results and TPT faster (intervention: median of 6 and 29 days after enrollment vs control: 21 and 54 days, respectively)., Interpretation: In this setting, QGIT in routine HIV care resulted in more patients with TBI results. Clinicians also initiated more people with HIV on TPT in QGIT intervention clinics, and did so more quickly, than the control arm., Clinical Trials Registration: NCT02119130., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Tuberculosis (TB) remains a global public health concern. The 2014 South African (SA) national TB management guidelines were developed to decrease the burden of TB, but implementation remains a challenge., Objectives: To estimate healthcare workers' level of knowledge about the national TB management guidelines and to assess the implementation of these guidelines., Methods: A cross-sectional descriptive study was conducted in four randomly selected health facilities in Dr Kenneth Kaunda district, North West Province, SA. We administered a TB knowledge questionnaire and reviewed TB registers and 204 patient files., Results: A total of 38 participants completed the TB knowledge questionnaire. The majority were professional nurses (89%). The participants' mean (standard deviation) age was 46 (8) years, and the median (interquartile range) career length was 10 (8 - 17) years. Inadequate knowledge of the national TB management guidelines was revealed in 12 participants (32%). The review of the TB register showed that 163 153 patients were screened for TB. Of these, 9 308 (6%) had presumptive TB, 8 116 (87%) had an Xpert test and 1 292 (16%) had positive Xpert results. Overall, 1 150 (12%) of the patients with presumptive TB were diagnosed with drug-sensitive TB and started treatment based on laboratory results and a clinical diagnosis. Of this sample, 999 patients (87%) were treated successfully. The patient file review showed that a total of 197 patients (97%) received the correct treatment dose according to body weight and treatment phase. Smear microscopy was consistently done throughout the intensive and continuation phases of TB treatment. Body weight was monitored in 199 patients (98%). Contact investigation was conducted for 133 patients (65%), and there was evidence that child contacts aged <5 years were started on isoniazid preventive therapy. Only 110 patients (54%) had documented HIV status. Of these, 66 (60%) were HIV positive, and 39 (59%) of them received antiretroviral therapy. Body mass index was monitored in 55 patients (27%). Eighty (39%) of the patients with TB were women of childbearing potential, and only 8 (10%) of them had their pregnancy test results recorded. Treatment side-effects were reported in 17 patient files (8%); 13 (76%) were managed and 8 (62%) had resolved side-effects., Conclusion: Most participants had adequate knowledge of the national TB management guidelines. A high TB treatment success rate was noted, along with some good practices. The study also highlights several knowledge and practice gaps that can be overcome by measures such as quality audits to improve record keeping. Adequate training of healthcare workers, sustaining and updating knowledge through continuous training, and strengthened supervision mechanisms to ensure compliance with the guidelines are recommended.

The nicotine metabolite ratio (NMR) is associated with race/ethnicity but has not been evaluated among smokers in the African region. We conducted a cross-sectional analysis of baseline data from a large randomized, controlled trial for smoking cessation among people with HIV (PWH) in South Africa. Urine samples were analyzed for the NMR and evaluated as a binary variable using a cutoff value of the fourth quartile to determine the fastest metabolizers. The median NMR was 0.31 (IQR: 0.31, 0.32; range: 0.29, 0.57); the cut-point for fast metabolizers was ≥0.3174 ng/mL. A high NMR was not associated with the number of cigarettes per day (OR = 1.10, 95% CI: 0.71, 1.70, p = 0.66) but was associated with 40% lower odds of a quit attempt in the past year (OR = 0.69; 95% CI: 0.44, 1.07, p = 0.09) and alcohol use (OR = 0.59, 95% CI: 0.32, 1.06, p = 0.07). No association was seen with marijuana or HIV clinical characteristics. As we found only minimal variability in the NMR and minimal associations with intensity of smoking, NMR may be of limited clinical value in this population, although it may inform which individuals are less likely to make a quit attempt.

In South Africa, high attrition rates throughout the care continuum present major barriers to controlling the HIV epidemic. Mobile health (mHealth) interventions may provide innovative opportunities for efficient healthcare delivery and improving retention in care. In this formative research, we interviewed 11 patients and 28 healthcare providers in North West Province, South Africa, to identify perceived benefits, concerns and suggestions for a future mHealth program to deliver HIV Viral Load and CD4 Count test results directly to patients via mobile phone. Thematic analysis found that reduced workload for providers, reduced wait times for patients, potential expanded uses and patient empowerment were the main perceived benefits of an mHealth program. Perceived concerns included privacy, disseminating distressing results through text messages and patients' inability to interpret results. Participants felt that an mHealth program should complement face-to-face interactions and educational information to interpret results is needed. Providers identified logistical considerations and suggested protocols be developed. An mHealth program to deliver HIV test results directly to patients could mitigate multiple barriers to care but needs to be tested for efficacy. Concerns identified by patients and providers must be addressed in designing the program to successfully integrate with health facility workflow and ensure its sustainability.

Isoniazid preventive therapy (IPT) reduces the risk of active tuberculosis among people living with HIV, but implementation of IPT in South Africa and elsewhere remains slow. The objective of this study was to examine both nurse perceptions of clinical mentorship and patient perceptions of in-queue health education for promoting IPT uptake in Potchefstroom, South Africa. We measured adoption, fidelity, acceptability, and sustainability of the interventions using both quantitative and qualitative methods. Adoption, fidelity, and acceptability of the interventions were moderately high. However, nurses believed they could not sustain their increased prescriptions of IPT, and though many patients intended to ask nurses about IPT, few did. Most patients attributed their behavior to an imbalance of patient-provider power. National IPT guidelines should be unambiguous and easily implemented after minimal training on patient eligibility and appropriate medication durations, nurse-patient dynamics should empower the patient, and district-level support and monitoring should be implemented.

Introduction: A higher proportion of people living with HIV (PLWH) smoke compared to the general population, but little information exists about the prevalence and correlates of smokeless tobacco use among PLWH. In South Africa, dry powdered tobacco is inhaled nasally as snuff., Methods: A cross-sectional survey among PLWH attending three HIV clinics was conducted. Snuff use was assessed via self-report and urine cotinine., Results: Given the low (3%) prevalence of snuff use among men, analysis was restricted to n = 606 nonsmoking women living with HIV. Half (n = 298, 49%) were snuff users, the majority of whom (n = 244, 84%) had a positive urine cotinine test. In adjusted analysis, snuff use was negatively associated with higher education (relative risk [RR] 0.55; 95% confidence interval [CI]: 0.39, 0.77) and mobile phone ownership (RR 0.83; 95% CI: 0.71, 0.98), and positively associated with ever having tuberculosis (TB) (RR 1.22; 95% CI: 1.03, 1.45). In adjusted analysis, with current TB as the outcome, snuff use was marginally statistically significantly associated with a twofold increase in odds of a current TB diagnosis (odds ratio [OR] 1.99; 95% CI: 0.98, 4.15)., Discussion: A high proportion of nonsmoking South African women living with HIV use snuff, which was a risk factor for TB. Additional research is needed to understand the relationship between snuff, TB, and other potential health risks., Implications: PLWH have a higher prevalence of smoking than their seronegative peers, but there is a paucity of research on smokeless tobacco use in this population, especially in low-resource settings. TB is the leading cause of death among PLWH, and with improvements to HIV treatment and care, PLWH are at greater risk of tobacco-related diseases. We report an extremely high prevalence of snuff use among women living with HIV in South Africa. Further, in this population snuff use is positively associated with ever having a TB diagnosis, as well as currently having TB., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The purpose of this prospective cohort study is to characterize the event of acute hospitalization for people living with and without HIV and describe its impact on the care continuum. This study describes care-seeking behavior prior to an index hospitalization, inpatient HIV testing and diagnosis, discharge instructions, and follow-up care for patients for patients being discharged from a single hospital in South Africa., Methods: A convenience sample of adult patients was recruited from the medical wards of a tertiary care facility. Baseline information at the time of hospital admission, subsequent diagnoses, and discharge instructions were recorded. Participants were prospectively followed with phone calls for six months after hospital discharge. Descriptive analyses were performed., Results: A total of 293 participants were enrolled in the study. Just under half (46%) of the participants were known to be living with HIV at the time of hospital admission. Most participants (97%) were given a referral for follow-up care; often that appointment was scheduled within two weeks of discharge (64%). Only 36% of participants returned to care within the first month, 50% returned after at least one month had elapsed, and 14% of participants did not return for any follow up., Conclusions: Large discrepancies were found between the type of post-discharge follow-up care recommended by providers and what patients were able to achieve. The period of time following hospital discharge represents a key transition in care. Additional research is needed to characterize patients' risk following hospitalization and to develop patient-centered interventions., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Smoking likely exacerbates comorbidities which people living with HIV (PLWH) are predisposed. We assessed prevalence and correlates of smoking among PLWH in South Africa, which has 7 million PLWH but inadequate reporting of smoking., Methods: A cross-sectional survey was conducted among randomly selected adults with HIV infection in Klerksdorp, South Africa. Current smoking was assessed by questionnaire, exhaled carbon monoxide (eCO), and urine cotinine., Results: Of 1210 enrolled adults, 753 (62%) were women. In total, 409 (34%) self-reported ever smoking: 301 (74%) were current and 108 (26%) were former smokers. Using eCO and urine cotinine tests, 239 (52%) men and 100 (13%) women were defined as current smokers. Nearly all smokers (99%) were receiving ART, and had a median (IQR) CD4 count of 333 cells/μL (181-534), viral load of 31 IU/mL (25-4750), and BMI of 21 kg/m2 (19-24). Adjusted analysis among men showed higher odds of smoking with marijuana use (OR = 7.5, 95% CI = 4.1 to 14.6). Among women, 304 (43%) reported using snuff, compared to only 11 (3%) of men, and snuff use was inversely associated with smoking (OR = 0.1; 95% CI = 0.05 to 0.2). A subset of participants (n = 336) was asked about alcohol use, which was positively associated with smoking for men (OR = 8.1, 95% CI = 2.8 to 25.9) and women (OR = 8.5, 95% CI = 2.9 to 26.8)., Conclusion: Smoking prevalence among PLWH in South Africa is alarmingly high. Prevention and cessation strategies that consider marijuana and alcohol use are needed., Implications: As long-term HIV care continues to improve, more people living with HIV (PLWH) will die of diseases, including tuberculosis, for which smoking plays an important causal role. The prevalence of smoking is markedly higher among PLWH in high-resource settings, but data for Africa and other low-resource settings that shoulder the brunt of the HIV epidemic has previously not been well documented. We report an alarmingly high prevalence of smoking among PLWH in South Africa, particularly among men, and a strong association between current smoking and use of other substances.

Introduction: Inefficient clinic-level delivery of HIV services is a barrier to linkage and engagement in care. We used value stream mapping to quantify time spent on each component of a clinic visit while receiving care following a hospital admission in South Africa., Methods: We described time for each clinic service ("process time") and time spent waiting for that service ("lead time"). We also determined time and patient costs associated with travel to the clinic and expenditures during the clinic visits for 15 clinic visits in South Africa. Participants were selected consecutively based on timing of scheduled clinic visit from a cohort of HIV-positive patients recently discharged from inpatient hospital care. During the mapping we asked the participants to assess challenges faced at the clinic visit. We subsequently conducted in depth interviews and included themes from the care experience in this analysis., Results: The 15 clinic visits occurred at five clinics; four primary care and one hospital-based specialty clinic. Nine (64%) of the participants were women, the median age was 44 years (IQR: 32-49), three of the participants had one or more clinic visit in the prior 14 days, all but one participant was on antiretroviral therapy (ART) at the time of the clinic visit (ART was stopped following the hospital visit for that participant). The median time since hospital discharge was 131 days (interquartile range; IQR: 121-183) for the observed visits. The median travel time to and from the clinic to a place of residence was 60 minutes. The median time spent at the clinic was 3.5 hours (IQR: 2.5-5.3) of which 2.9 hours was lead time and 25 minutes was process time (registration, vital signs, clinician assessment, laboratory, and check-out). The median patient cost for transport and food while at the clinic was ZAR43/USD2.8 (median monthly household income in the district was ZAR2450/USD157). Participants highlighted long queues, repeat clinic visits, and multiple queues during the visit (median of 5 queues) as challenges., Conclusions: Accessing HIV care in South Africa is time consuming, complicated by multiple queues and frequent visits. A more patient-centered approach to care may decrease the burden of receiving care and improve outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Tuberculosis (TB) is the leading cause of mortality among people living with HIV (PLHIV), despite the availability of effective preventive therapy. The TEKO trial is assessing the impact of using a blood test, Quantiferon-TB Gold In-Tube Test (QGIT), to screen for latent TB compared to the Tuberculin Screening Test (TST) among PLHIV in South Africa., Methods: Fifty-six qualitative interviews were conducted with PLHIV and clinical providers participating in the TEKO trial. We explored TB screening, diagnosis, and treatment guidelines and processes and the use of the QGIT to screen for latent TB infection at the time of CD4 blood draw. Thematic content analysis was conducted., Results: Considerable variability in TB screening procedures was documented due to lack of personnel and clarity regarding current national TB guidelines for PLHIV. Few clinics had started using the TST per national guidelines and many patients had never heard of isoniazid preventive therapy (IPT). Nearly all participants supported the idea of latent TB screening using routine blood drawn for CD4 counts., Conclusions: Findings indicate that screening for latent TB infection using QGIT from blood drawn for CD4 counts among PLHIV is an acceptable approach to increase latent TB detection given the challenges associated with ensuring systematic latent TB screening in overburdened public clinics., Trial Registration: The results presented here were from formative research related to the TEKO trial (Identifier NCT02119130 , registered 10 April 2014).

There are limited data describing acute kidney injury (AKI) in HIV-infected adult patients in resource-limited settings where tenofovir disoproxil fumarate (TDF), which is potentially nephrotoxic, is increasingly prescribed. We describe risk factors for and prognosis of AKI in HIV-infected individuals, stratified by those receiving and those naive to TDF. A prospective case cohort study of hospitalized HIV-infected adults with AKI stratified by TDF exposure. Adults (≥18 years) were recruited: clinical and biochemical data were collected at admission; their renal recovery, discharge, or mortality was ascertained as an in-patient and, subsequently, to a scheduled 3-month follow-up. Among this predominantly female (61%), almost exclusively black African cohort of 175 patients with AKI, 93 (53%) were TDF exposed; median age was 41 years (interquartile range 35-50). Median CD4 count and viral load and creatinine at baseline were 116 cells/mm 3 and 110,159 copies/ml, respectively. A greater proportion of the TDF group had severe AKI on admission (61% vs. 43%, p = .014); however, both groups had similar rates of newly diagnosed tuberculosis (TB; 52%) and nonsteroidal anti-inflammatory drug (NSAID; 32%) use. Intravenous fluid was the therapeutic mainstay; only seven were dialyzed. Discharge median serum creatinine (SCr) was higher in the TDF group (p = .032) and fewer in the TDF group recovered renal function after 3 months (p = .043). Three-month mortality was 27% in both groups, but 55% of deaths occurred in hospital. Those that died had a higher SCr and more severe AKI than survivors; TB was diagnosed in 33 (70%) of those who died. AKI was more severe and renal recovery slower in the TDF group; comorbidities, risk factors, and prognosis were similar regardless of TDF exposure. Because TB is linked to higher mortality, TB coinfection in HIV-infected patients with AKI warrants more intensive monitoring. In all those with poor renal recovery, our data suggest that a lower threshold for dialysis is needed., Competing Interests: Author Disclosure Statement No competing financial interests exist.