A Cross-Sectional Analysis of the Nicotine Metabolite Ratio and Its Association with Sociodemographic and Smoking Characteristics among People with HIV Who Smoke in South Africa.

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.

Use of Epidemiology Surge Support to Enhance Robustness and Expand Capacity of SARS-CoV-2 Pandemic Response, South Africa.

As COVID-19 cases increased during the first weeks of the pandemic in South Africa, the National Institute of Communicable Diseases requested assistance with epidemiologic and surveillance expertise from the US Centers for Disease Control and Prevention South Africa. By leveraging its existing relationship with the National Institute of Communicable Diseases for >2 months, the US Centers for Disease Control and Prevention South Africa supported data capture and file organization, data quality reviews, data analytics, laboratory strengthening, and the development and review of COVID-19 guidance This case study provides an account of the resources and the technical, logistical, and organizational capacity leveraged to support a rapid response to the COVID-19 pandemic in South Africa.

Cohort profile: A Prospective Household cohort study of Influenza, Respiratory syncytial virus and other respiratory pathogens community burden and Transmission dynamics in South Africa, 2016-2018.

PURPOSE: The PHIRST study (Prospective Household cohort study of Influenza, Respiratory Syncytial virus, and other respiratory pathogens community burden and Transmission dynamics in South Africa) aimed to estimate the community burden of influenza and respiratory syncytial virus (RSV) including the incidence of infection, symptomatic fraction, and to assess household transmission. PARTICIPANTS: We enrolled 1684 individuals in 327 randomly selected households in a rural and an urban site over three consecutive influenza and two RSV seasons. A new cohort of households was enrolled each year. Participants were sampled with nasopharyngeal swabs twice-weekly during the RSV and influenza seasons of the year of enrolment. Serology samples were collected at enrolment and before and after the influenza season annually. FINDINGS TO DATE: There were 122 113 potential individual follow-up visits over the 3 years, and participants were interviewed for 105 783 (87%) of these. Out of 105 683 nasopharyngeal swabs, 1258 (1%) and 1026 (1%) tested positive on polymerase chain reaction (PCR) for influenza viruses and RSV, respectively. Over one third of individuals had PCR-confirmed influenza each year. Overall, there was influenza transmission to 10% of household contacts of an index case. FUTURE PLANS: Future planned analyses include analysis of influenza serology results and RSV burden and transmission. Households enrolled in the PHIRST study during 2016-2018 were eligible for inclusion in a study of SARS-CoV-2 transmission initiated in July 2020. This study uses similar testing frequency to assess the community burden of SARS-CoV-2 infection and the role of asymptomatic infection in virus transmission.

Promoting Tuberculosis Preventive Therapy for People Living with HIV in South Africa: Interventions Hindered by Complicated Clinical Guidelines and Imbalanced Patient-Provider Dynamics.

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.

Formative research for an mHealth program to improve the HIV care continuum in South Africa.

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.

Improving Tuberculosis Preventive Therapy Uptake: A Cluster-randomized Trial of Symptom-based Versus Tuberculin Skin Test-based Screening of Household Tuberculosis Contacts Less Than 5 Years of Age.

BACKGROUND: Tuberculosis preventive therapy (TPT) is highly effective at preventing tuberculosis disease in household child contacts (<5 years), but is poorly implemented worldwide. In 2006, the World Health Organization recommended symptom-based screening as a replacement for tuberculin skin testing (TST) to simplify contact evaluation and improve implementation. We aimed to determine the effectiveness of this recommendation. METHODS: We conducted a pragmatic, cluster-randomized trial to determine whether contact evaluation using symptom screening improved the proportion of identified child contacts who initiated TPT, compared to TST-based screening, in Matlosana, South Africa. We randomized 16 clinics to either symptom-based or TST-based contact evaluations. Outcome data were abstracted from customized child contact management files. RESULTS: Contact tracing identified 550 and 467 child contacts in the symptom and TST arms, respectively (0.39 vs 0.32 per case, respectively; P = .27). There was no significant difference by arm in the adjusted proportion of identified child contacts who were screened (52% in symptom arm vs 60% in TST arm; P = .39). The adjusted proportion of identified child contacts who initiated TPT or tuberculosis treatment was 51.5% in the symptom clinics and 57.1% in the TST clinics (difference -5.6%, 95% confidence interval -23.7 to 12.6; P = .52). Based on the district's historic average of 0.7 child contacts per index case, 14% and 15% of child contacts completed 6 months of TPT in the symptom and TST arms, respectively (P = .89). CONCLUSIONS: Symptom-based screening did not improve the proportion of identified child contacts evaluated or initiated on TPT, compared to TST-based screening. Further research is needed to identify bottlenecks and evaluate interventions to ensure all child contacts receive TPT. CLINICAL TRIALS REGISTRATION: NCT03074799.

Prevalence and Correlates of Snuff Use, and its Association With Tuberculosis, Among Women Living With HIV in South Africa.

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.

Hospitalization and post-discharge care in South Africa: A critical event in the continuum of care.

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.

Value stream mapping to characterize value and waste associated with accessing HIV care in South Africa.

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.

Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen CD4 blood draws for latent TB infection among PLHIV in South Africa: formative qualitative research findings from the TEKO trial.

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).

Prevalence and Correlates of Smoking Among People Living With HIV in South Africa.

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.

Indoor air pollution from secondhand tobacco smoke, solid fuels, and kerosene in homes with active tuberculosis disease in South Africa.

OBJECTIVES: Secondhand tobacco smoke (SHS), use of solid fuels, and kerosene may play an important role in perpetuating the tuberculosis (TB) epidemic. The purpose of this study was to explore the prevalence of household air pollution (HAP) from these sources in homes of someone with TB in a high HIV-prevalence setting. A convenience sample of homes and household members participating in an ongoing active case-finding study in Matlosana district townships surrounding Klerksdorp, South Africa were included. RESULTS: We found a high prevalence of air pollution from SHS, solid fuels, and kerosene among individuals in homes with a case of prevalent active TB disease in Klerksdorp, South Africa. Adults in 40% of homes reported a daily smoker in the home, and 70% of homes had detectable air nicotine. In homes with a history of previous TB (prior to but not including the index case) as compared to those without previous TB, both SHS (83% vs. 65%, respectively) and solid/kerosene fuel use for more than 1 h/day (27% vs. 21%, respectively) were more prevalent. Larger studies are needed to estimate the risk of TB from these types of air pollution in HIV infected individuals and settings with high HIV prevalence.

Acute Kidney Injury, Risk Factors, and Prognosis in Hospitalized HIV-Infected Adults in South Africa, Compared by Tenofovir Exposure.

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/mm3 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.

The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa.

Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB treatment. 863 (53%) participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62-3.78) were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52-2.68). Discussion and Conclusions. Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield.

Knowledge, attitudes, and practices about influenza illness and vaccination: a cross-sectional survey in two South African communities.

BACKGROUND: Understanding knowledge and sentiment toward influenza and vaccination is important for effective health messages and prevention strategies. We aimed to characterize knowledge, attitudes, and practices surrounding influenza illness and vaccination in two South African communities and explore reasons for vaccine hesitancy. METHODS: Household primary caregivers in Soweto and Klerksdorp townships were interviewed about knowledge of influenza and intention to receive an influenza vaccine using a structured questionnaire. Factors associated with unwillingness to receive vaccine were explored using multivariable regression. RESULTS: We interviewed representatives of 973 households in Soweto and 1,442 in Klerksdorp. Most respondents in Soweto (692, 71%) and Klerksdorp (1247, 87%) thought weather or cold caused influenza. While most would get a free influenza vaccine, those unwilling to receive vaccine had concerns about efficacy (Soweto: 19%; Klerksdorp: 19%) and safety (Soweto: 17%; Klerksdorp: 10%). In Soweto, females (aRR 2·0, 95% CI 1·3-3·2) and those with higher household income (aRR 1·8, 95% CI 1·2-2·7) were less willing to receive vaccine. In Klerksdorp, more educated respondents (aRR 1·6, 95% CI 1·1-2·4) were less willing to receive vaccine; households reporting an HIV-positive member were more willing to receive vaccine (aRR 0·3, 95% CI 0·1-0·8). CONCLUSIONS: Although findings suggest most community participants were amenable to influenza vaccination, knowledge gaps were present. Emphasizing the importance of influenza as a health problem and addressing vaccine safety and efficacy concerns may improve uptake. Populations less amenable to vaccination, including those with higher education and income, may benefit from targeted messaging efforts.