Experiences of participants in a decentralized antiretroviral therapy program in South Africa during the COVID-19 pandemic.

The COVID-19 pandemic and associated restrictions could adversely affect long-term HIV care. We evaluated the experiences of people receiving antiretroviral therapy (ART) through a decentralized delivery program in South Africa during the COVID-19 pandemic. We telephoned a random subsample of participants enrolled in a prospective cohort study in KwaZulu-Natal in April and May 2020 and administered a semi-structured telephone interview to consenting participants. We completed interviews with 303 of 638 contacted participants (47%); 66% were female, with median age 36y. The most common concerns regarding the COVID-19 pandemic were food running out (121, 40%), fear of becoming infected with COVID-19 (103, 34%), and being unable to work/losing employment or income (102, 34%). Twenty-five (8%) participants had delayed ART pick-up due to the pandemic, while 212 (70%) had new concerns about ART access going forward. Mental health scores were worse during the pandemic compared to baseline (median score 65.0 vs 80.0, p < 0.001). Decentralized ART distribution systems have the potential to support patients outside of health facilities during the COVID-19 pandemic, but economic concerns and mental health impacts related to the pandemic must also be recognized and addressed.

Medical Mistrust and Stigma Associated with COVID-19 Among People Living with HIV in South Africa.

We evaluated COVID-19 stigma and medical mistrust among people living with HIV in South Africa. We conducted telephone interviews with participants in a prospective study of a decentralized antiretroviral therapy program. Scales assessing medical mistrust, conspiracy beliefs, anticipated and internalized stigma, and stereotypes specific to COVID-19 were adapted primarily from the HIV literature, with higher scores indicating more stigma or mistrust. Among 303 participants, the median stigma summary score was 4 [interquartile range (IQR) 0-8; possible range 0-24] and 6 (IQR 2-9) for mistrust (possible range 0-28). A substantial proportion of participants agreed or strongly agreed with at least one item assessing stigma (54%) or mistrust (43%). Higher COVID-19 stigma was associated with female gender and antecedent HIV stigma, and lower stigma with reporting television as a source of information on COVID-19. Further efforts should focus on effects of stigma and mistrust on protective health behaviors and vaccine hesitancy.

Laboratory Reflex and Clinic-Based Point-of-Care Cryptococcal Antigen Screening for Preventing Meningitis and Mortality Among People Living With HIV.

INTRODUCTION: Cryptococcosis remains a leading cause of meningitis and mortality among people living with HIV (PLHIV) worldwide. We sought to evaluate laboratory-based cryptococcal antigen (CrAg) reflex testing and a clinic-based point-of-care (POC) CrAg screening intervention for preventing meningitis and mortality among PLHIV in South Africa. METHODS: We conducted a prospective pre-post intervention study of adults presenting for HIV testing in Umlazi township, South Africa, over a 6-year period (2013-2019). Participants were enrolled during 3 phases of CrAg testing: CrAg testing ordered by a clinician (clinician-directed testing, 2013-2015); routine laboratory-based CrAg reflex testing for blood samples with CD4 ≤100 cells/mm3 (laboratory reflex testing, 2015-2017); and a clinic-based intervention with POC CD4 testing and POC CrAg testing for PLHIV with CD4 ≤200 cells/mm3 with continued standard-of-care routine laboratory reflex testing among those with CD4 ≤100 cells/mm3 (clinic-based testing, 2017-2019). The laboratory and clinical teams performed serum CrAg by enzyme immunoassay and lateral flow assay (Immy Diagnostics, Norman, OK). We followed up participants for up to 14 months to compare associations between baseline CrAg positivity, antiretroviral therapy and fluconazole treatment initiation, and outcomes of cryptococcal meningitis, hospitalization, and mortality. RESULTS: Three thousand one hundred five (39.4%) of 7877 people screened were HIV-positive, of whom 908 had CD4 ≤200 cells/mm3 and were included in the analyses. Laboratory reflex and clinic-based testing increased CrAg screening (P < 0.001) and diagnosis of CrAg-positive PLHIV (P = 0.011). When compared with clinician-directed testing, clinic-based CrAg testing showed an increase in the number of PLHIV diagnosed with cryptococcal meningitis (4.5% vs. 1.5%; P = 0.059), initiation of fluconazole preemptive therapy (7.2% vs. 2.5%; P = 0.010), and initiation of antiretroviral therapy (96.8% vs. 91.3%; P = 0.012). Comparing clinic-based testing with laboratory reflex testing, there was no significant difference in the cumulative incidence of cryptococcal meningitis (4.5% vs. 4.1%; P = 0.836) or mortality (8.1% vs. 9.9%; P = 0.557). CONCLUSIONS: Laboratory reflex and clinic-based CrAg testing facilitated the diagnosis of HIV-associated cryptococcosis and fluconazole initiation but did not reduce cryptococcal meningitis or mortality. In this nonrandomized cohort, clinical outcomes were similar between laboratory reflex testing and clinic-based POC CrAg testing.

Tuberculosis-related stigma among adults presenting for HIV testing in KwaZulu-Natal, South Africa.

BACKGROUND: Tuberculosis (TB)-related stigma presents a major barrier to care of persons with TB through its impact on treatment initiation and retention in care. This is particularly challenging in settings with high prevalence of both TB and HIV where fear of HIV/AIDS can amplify stigma surrounding TB. The purpose of this study was to validate a TB stigma scale for use among persons presenting for outpatient HIV screening in the Umlazi township of South Africa and evaluate factors associated with TB-related stigma in this high HIV burden setting. METHODS: In this cross-sectional study, we measured TB-related stigma in adults prior to HIV testing using a 12-item scale designed to assess experienced and felt TB-related stigma. RESULTS: Among 848 adults, mean age was 32 years, 54% were male, and the median TB stigma score was 19 of 36 (interquartile range 15-23). We identified two factors in the stigma scale which had excellent reliability (Cronbach's alpha 0.85, 0.89). Persons with high TB stigma were more likely to be male (adjusted relative risk ratio [aRRR] 1.56, 95% confidence interval [CI] 1.11-2.28) and have accurate knowledge of TB transmission (aRRR 1.90, 95% CI 1.16-3.10) as compared to those with low stigma. Variables not significantly associated with stigma in the multivariate model included education, income, prior TB or HIV diagnoses, and depression. CONCLUSIONS: Male sex and TB knowledge were associated with higher TB stigma in an outpatient HIV clinic in a South African township. Identifying risk factors associated with stigma will be important to guide stigma reduction interventions.

Contraception, HIV Services, and PrEP in South African Hair Salons: A Qualitative Study of Owner, Stylist, and Client Perspectives.

Women experience challenges engaging with the healthcare system, but frequently utilize hair salons; these are promising venues for family planning and HIV prevention services. Our objective was to assess the acceptability of nurse-offered contraceptive and PrEP services at hair salons in Durban, South Africa. We interviewed salon owners (N = 10) and clients (N = 42) and conducted focus groups with hair stylists (N = 43 stylists; 6 focus groups across five hair salons) to explore barriers and facilitators to providing contraception and PrEP in salons. After developing a codebook, we performed content analysis to identify themes within each conceptual area; 10% of transcripts were coded by two coders to ensure reliability. Content was analyzed according to the following categories: (1) facilitators of and (2) barriers to utilizing these services, and (3) factors to consider for program implementation. Participants identified convenience and female-oriented, supportive atmosphere as facilitators to offering HIV and contraceptive services in salons. Owners and stylists noted that establishing legitimacy was important for program success, including providing promotional pamphlets and employing nurses. Clients cited privacy concerns surrounding HIV testing in a public space as a significant barrier to using these services. Overall, participants were enthusiastic about the program. Convenience and a conducive environment were noted as facilitators to receiving health services in the hair salon; attention will have to be directed to establishing privacy and program legitimacy. Hair salons represent an innovative venue for reaching young women at high-risk for unintended pregnancy and HIV infection.

Validation of clinic-based cryptococcal antigen lateral flow assay screening in HIV-infected adults in South Africa.

Since rapid cryptococcal antigen lateral flow assays (CrAg LFA) may expedite treatment of HIV-associated cryptococcal infections, we sought to validate clinic-based CrAg LFA testing. Among newly-diagnosed HIV-infected adults in South Africa, a trained nurse performed clinic-based testing of urine, fingerprick capillary and venous whole blood with rapid CrAg LFA (Immy Diagnostics, Norman, USA). We performed matched laboratory-based serum cryptococcal antigen testing with an enzyme immunoassay (EIA). We assessed diagnostic accuracy using EIA as the gold-standard, and performed additional validation testing on serum and among hospitalized adults with cryptococcal meningitis. Among 5,618 participants enrolled, 1,296 were HIV-infected and screened for cryptococcal antigenemia. Overall CrAg prevalence by serum EIA was 3.6% (95% CI 2.0-6.0%) for adults with CD4 < 200 cells/mm3, and 5.7% (95% CI 2.8-10.2%) for adults with CD4 < 100 cells/mm3. Using expanded screening guidelines (CD4 < 200 cells/mm3), CrAg LFA testing of venous whole blood, fingerprick capillary blood, and urine had diagnostic sensitivities of 46% (95% CI 19-75%), 38% (95% CI 14-68%), and 54% (95% CI 25-81%), and specificities of 97%, 97%, and 86%, respectively. When tested on serum samples, CrAg LFA had sensitivity of 93% (95% CI 66-100%) and specificity of 100% (95% CI 88-100%). All venous and fingerprick whole blood CrAg LFA tests were positive among 30 hospitalized adults with cryptococcal meningitis. Two independent readers had strong agreement for all LFA results (p < 0.0001). When performed at the point-of-care by trained nurses, CrAg LFA testing was feasible, had the highest accuracy on serum specimens, and may accelerate treatment of HIV-associated cryptococcal infections.

Integrating hypertension screening at the time of voluntary HIV testing among adults in South Africa.

BACKGROUND: Guidelines recommend integrating hypertension screening for HIV-infected adults, but blood pressure measurements may be dynamic around the time of HIV testing. METHODS: We measured a seated resting blood pressure in adults (≥18 years) prior to HIV testing, and again after receiving HIV test results, in an ambulatory HIV clinic in KwaZulu-Natal, South Africa. We assessed sociodemographics, smoking, body mass index, diabetes, substance abuse, and anxiety/depression. We used blood pressure categories defined by the Seventh Joint National Committee (JNC 7) classifications, which includes normal, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. RESULTS: Among 5,428 adults, mean age was 31 years, 51% were male, and 35% tested HIV-positive. Before HIV testing, 47% (2,634) had a normal blood pressure, 40% (2,225) had prehypertension, and 10% (569) had stage 1 or 2 hypertension. HIV-infected adults had significantly lower blood pressure measurements and less hypertension, as compared to HIV-negative adults before HIV testing; while also having significantly elevated blood pressures after HIV testing. In a multivariable model, HIV-infected adults had a 30% lower odds of hypertension, compared to HIV-uninfected adults (aOR = 0.70, 95% CI: 0.57-0.85). In a separate multivariable model, HIV-infected adults with CD4 ≤200 cells/mm3 had a 44% lower odds of hypertension (aOR = 0.56, 95% CI: 0.38-0.83), as compared to adults with CD4 >200 cells/mm3. The mean arterial blood pressure was 6.5 mmHg higher among HIV-infected adults after HIV testing (p <0.001). CONCLUSIONS: HIV-infected adults experienced a transient blood pressure increase after receiving HIV results. Blood pressure measurements may be more accurate before HIV testing and repeated blood pressure measurements are recommended after ART initiation before formally diagnosing hypertension in HIV-infected adults.

Test and Treat TB: a pilot trial of GeneXpert MTB/RIF screening on a mobile HIV testing unit in South Africa.

BACKGROUND: Community-based GeneXpert MTB/RIF testing may increase detection of prevalent TB in the community and improve rates of TB treatment completion. METHODS: We conducted a pilot randomized trial to evaluate the impact of GeneXpert screening on a mobile HIV testing unit. Adults (≥18y) underwent rapid HIV testing and TB symptom screening and were randomized to usual mobile unit care (providing sputum on the mobile unit sent out for GeneXpert testing) or the "Test & Treat TB" intervention with immediate GeneXpert testing. Symptomatic participants in usual care produced sputum that was sent for hospital-based GeneXpert testing; participants were contacted ~ 7 days later with results. In the "Test & Treat TB" intervention, HIV-infected or HIV-uninfected/TB symptomatic participants underwent GeneXpert testing on the mobile unit. GeneXpert+ participants received expedited TB treatment initiation, monthly SMS reminders and non-cash incentives. We assessed 6-month TB treatment outcomes. RESULTS: 4815 were eligible and enrolled; median age was 27 years (IQR 22 to 35). TB symptoms included cough (5%), weight loss (4%), night sweats (4%), and fever (3%). 42% of eligible participants produced sputum (intervention: 56%; usual care: 26%). Seven participants tested GeneXpert+, six in the intervention (3%, 95% CI 1%, 5%) and one in usual care (1%, 95% CI 0%, 6%). 5 of 6 intervention participants completed TB treatment; the GeneXpert+ participant in usual care did not. CONCLUSION: GeneXpert MTB/RIF screening on a mobile HIV testing unit is feasible. Yield for GeneXpert+ TB was low, however, the "Test & Treat TB" strategy led to high rates of TB treatment completion. TRIAL REGISTRATION: This study was registered on November 21, 2014 at ClinicalTrials.gov ( NCT02298309 ).

C-reactive protein as a screening test for HIV-associated pulmonary tuberculosis prior to antiretroviral therapy in South Africa.

BACKGROUND: There is an urgent need for more accurate screening tests for tuberculosis(TB). We assessed the diagnostic accuracy of C-reactive protein (CRP) as a screening test for active TB in HIV-infected ambulatory adults. METHODS: CRP levels were measured in blood collected at the time of HIV testing.Diagnostic accuracy of CRP for pulmonary TB was calculated (reference standard: TB culture), compared to the WHO 4-symptom screen, consisting of cough, fever, night sweats, and weight loss. Diagnostic accuracy was also calculated for CRP in a larger cohort of HIV-infected adults with a positive symptom screen (reference standard: clinical or microbiological TB). RESULTS: Among 425 HIV-infected outpatients systematically tested for pulmonary TB, TB culture was positive in 42 (10%), 279 (66%) had at least one TB-related symptom and 197 (46%) had a CRP more than 5 mg/l. The sensitivity of CRP and the TB symptom screen to detect TB was the same [90.5%; 95% confidence interval 77.4-97.3] but specificity of CRP was higher than for the TB symptom screen (58.5% vs. 37.1%, P < 0.001). Of persons with no symptoms and normal CRP, 99 (98%) had no TB. In another cohort of 749 patients presenting with at least one TB-related symptom and clinically evaluated, CRP had a sensitivity of 98.7% and specificity of 48.3%. CONCLUSION: In HIV-infected outpatients, CRP was as sensitive but substantially more specific than TB symptom screening. Use of CRP as a screening tool to exclude active TB could identify the same number of HIV-associated TB cases, but reduce the use of diagnostic sputum testing in TB-endemic regions.

Depression and Anxiety as Risk Factors for Delayed Care-Seeking Behavior in Human Immunodeficiency Virus-Infected Individuals in South Africa.

Background: Facility- and community-based efforts to improve human immunodeficiency virus (HIV) testing in sub-Saharan Africa may benefit from understanding how mental health influences HIV care-seeking behavior. Methods: We conducted a study among adults presenting for HIV testing in the Umlazi township of South Africa. Prior to testing, we measured depression using the 9-item Patient Health Questionnaire and anxiety using the 7-item Generalized Anxiety Disorder scale. We categorized patients as delayed presenters (presenting to clinic >3 months after first HIV-positive test), late testers (presenting within 3 months of diagnosis with a CD4 count ≤200 cells per µL), or neither. We used multinomial logistic regression adjusting for sociodemographic and behavioral characteristics to determine the effects of depression and anxiety on HIV care-seeking behavior. Results: Among 1482 HIV-infected adults, 59% were female and mean age was 33 years. The prevalence of depression in the cohort was 33% and anxiety was 9%. In adjusted models, mild to moderate depression was not associated with delayed presentation or late testing. HIV-infected adults with severe depression had 3.6 greater odds (95% confidence interval [CI], 1.2-10.2) of delayed presentation and 2.2 greater odds (95% CI, 1.01-4.8) of late testing compared with those without depression. Individuals with generalized anxiety had 2.3 greater odds (95% CI, 1.3-4.2) of delayed presentation compared with those without anxiety. Conclusions: Severe depression was associated with delayed presentation and late testing, while anxiety was associated only with delayed presentation. Screening for mental health services may improve antiretroviral therapy initiation and linkage to care following HIV testing.

Finding HIV in hard to reach populations: mobile HIV testing and geospatial mapping in Umlazi township, Durban, South Africa.

Mobile, community-based HIV testing may help achieve universal HIV testing in South Africa. We compared the yield, geographic distribution, and demographic characteristics of populations tested by mobile- and clinic-based HIV testing programs deployed by iThembalabantu Clinic in Durban, South Africa. From July to November 2011, 4,701 subjects were tested; HIV prevalence was 35 % among IPHC testers and 10 % among mobile testers (p < 0.001). Mobile testers varied in mean age (22-37 years) and % males (26-67 %). HIV prevalence at mobile sites ranged from 0 to 26 %. Testers traveled further than the clinic closest to their home; mobile testers were more likely to test ≥5 km away from home. Mobile HIV testing can improve testing access and identify testing sites with high HIV prevalence. Individuals often access mobile testing sites farther from home than their nearest clinic. Geospatial techniques can help optimize deployment of mobile units to maximize yield in hard-to-reach populations.

Starting a home and mobile HIV testing service in a rural area of South Africa.

OBJECTIVE: To compare users of a home and mobile HIV counseling and testing service implemented in rural KwaZulu-Natal, South Africa. METHODS: Communities of similar population size and density were allocated HIV counseling and testing provision be either home or mobile services. Uptake of services was compared, including results from a brief questionnaire. RESULTS: Majority of individuals proceeded to test. Mobile services reported a higher proportion of clients who were male (41% vs. 31%; P < 0.001), younger than 25 years (53% vs. 28%; P < 0.001), single (66% vs. 40%; P < 0.001), and never previously tested (62% vs. 56%; P = 0.003). Home services reported a higher proportion of clients older than of 35 years (56% vs. 35%; P < 0.001) and married/partner (43% vs. 30%; P < 0.001). HIV prevalence amongst clients of the 2 services was comparable, with both services testing more clients daily than the local primary health care clinics, but similar to the local hospital. CONCLUSIONS: The numbers tested, different populations reached, and high detection rates suggest both modalities have an important role to play, especially in rural communities where cost of transport may be a deterrent.

Need for timely paediatric HIV treatment within primary health care in rural South Africa.

BACKGROUND: In areas where adult HIV prevalence has reached hyperendemic levels, many infants remain at risk of acquiring HIV infection. Timely access to care and treatment for HIV-infected infants and young children remains an important challenge. We explore the extent to which public sector roll-out has met the estimated need for paediatric treatment in a rural South African setting. METHODS: Local facility and population-based data were used to compare the number of HIV infected children accessing HAART before 2008, with estimates of those in need of treatment from a deterministic modeling approach. The impact of programmatic improvements on estimated numbers of children in need of treatment was assessed in sensitivity analyses. FINDINGS: In the primary health care programme of HIV treatment 346 children <16 years of age initiated HAART by 2008; 245(70.8%) were aged 10 years or younger, and only 2(<1%) under one year of age. Deterministic modeling predicted 2,561 HIV infected children aged 10 or younger to be alive within the area, of whom at least 521(20.3%) would have required immediate treatment. Were extended PMTCT uptake to reach 100% coverage, the annual number of infected infants could be reduced by 49.2%. CONCLUSION: Despite progress in delivering decentralized HIV services to a rural sub-district in South Africa, substantial unmet need for treatment remains. In a local setting, very few children were initiated on treatment under 1 year of age and steps have now been taken to successfully improve early diagnosis and referral of infected infants.