The "ART" of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban, South Africa

BACKGROUND. Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa. METHODOLOGY/PRINCIPAL FINDINGS. We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived =10 kilometers from the testing center (RR=1.37; 95% CI: 1.11-1.71), had a history of tuberculosis treatment (RR=1.26; 95% CI: 1.00-1.58), or were referred for testing by a health care provider rather than self-referred (RR=1.61; 95% CI: 1.22-2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors. CONCLUSIONS/SIGNIFICANCE. Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.US National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, K23 AI068458); the Harvard University Center for AIDS Research (P30 AI42851); National Institutes of Health (K24 AR 02123); the Doris Duke Charitable Foundation (Clinical Scientist Development Award); the Harvard University Program on AID

HIV Self-testing and the Missing Linkage

Rochelle Walensky and Ingrid Bassett discuss new research in <I>PLoS Medicine</I> that assessed the feasibility of home-based oral HIV self-testing in Malawi, and suggest that linkage to care must be demonstrated before the success of oral self-testing can be determined

Linkage to HIV, TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town, South Africa

Background: HIV counseling and testing may serve as an entry point for non-communicable disease screening. Objectives: To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. Methods: A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. Results: Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. Conclusion: Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care

Urine lipoarabinomannan to monitor antituberculosis therapy response and predict mortality in an HIV-endemic region: a prospective cohort study.

CAPRISA, 2015.Abstract available in pdf

Effect of perceived HIV risk on initiation of antiretroviral therapy during the universal test and treat era in South Africa

BACKGROUND : South Africa has not achieved the 90–90–90 goals, in part due to low rates of antiretroviral therapy (ART) initiation among those aware of their HIV status. Perceived risk of HIV at the time of testing may affect likelihood of rapid ART initiation. The purpose of this study was to evaluate factors associated with perceived risk of HIV and the relationship between perceived HIV risk and rapid ART initiation during the universal test and treat era which was adapted in October 2016. METHODS : We conducted a prospective study of adults undergoing HIV testing from October 2016–February 2019 at Ithembalabantu Clinic in Durban. Eligible participants reported not previously being diagnosed with HIV. Before HIV testing, participants were asked to assess their perceived HIV risk on a four-level scale. We categorized “definitely not” and “probably not going to acquire HIV” as a low perceived risk, and “probably will” and “definitely will become HIVinfected” as a high perceived risk of HIV infection. Participants were followed for up to 14 months following HIV testing to assess ART initiation. RESULTS : Among 1519 people newly diagnosed with HIV, 55% were female and mean age was 33 years. Among those, 1382 (90.9%) had a high HIV risk perception and 137 (9.1%) reported low HIV risk perception. In the low risk group individuals were more likely to be female (58% vs 55%), unemployed (62% vs 59%), have a partner with unknown HIV status (61% vs 55%) compared to the high risk group. 83.2% of those with low HIV risk perception reported previously HIV testing compared 91.5% of those with high HIV risk perception. In the multivariate model, males were associated with a higher chances of initiating ART compared to females (adjusted hazard ratio (aHR): 1.187, CI 1.187 (1.060–1.329) and being unemployed (aHR 0.767 CI (0.650–0.905). Those with a low HIV risk perception were less likely to initiate ART 125 (91%) vs 1310 (95%) p = 0.022), and took longer to initiate on ART after HIV diagnosis (11 days’ vs 4 days, p = 0.042). CONCLUSION : Factors associated with high HIV risk perception included being unemployed, single, and having a partner of unknown HIV status. People living with HIV (PLHIV) in South Africa who had a low self-perceived risk to HIV infection were less likely to initiate ART. Assessing self-perceived risk of HIV infection may help direct counselling and improve ART initiation to achieve universal 90–90–90 goal.The Infectious Disease Society of America Education & Research Foundation and National Foundation for Infectious Diseases; Massachusetts General Hospital Executive Committee on Research; the Harvard University Centre for AIDS Research; and the National Institute of Allergy and Infectious Diseases.https://bmcinfectdis.biomedcentral.comam2022School of Health Systems and Public Health (SHSPH

The Clinical and Economic Impact of Point-of-Care CD4 Testing in Mozambique and Other Resource-Limited Settings: A Cost-Effectiveness Analysis

Background: Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique. Methods and Findings: We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9$2,440 (95% CI, US$2,440–US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3–10.3 y) and US$2,800 (95$2,790–US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480–US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4. Conclusions: POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors' Summar

A randomized trial to optimize HIV/TB care in South Africa: design of the Sizanani trial

Background: Despite increases in HIV testing, only a fraction of people newly diagnosed with HIV infection enter the care system and initiate antiretroviral therapy (ART) in South Africa. We report on the design and initial enrollment of a randomized trial of a health system navigator intervention to improve linkage to HIV care and TB treatment completion in Durban, South Africa. Methods/Design We employed a multi-site randomized controlled trial design. Patients at 4 outpatient sites were enrolled prior to HIV testing. For all HIV-infected participants, routine TB screening with sputum for mycobacterial smear and culture were collected. HIV-infected participants were randomized to receive the health system navigator intervention or usual care. Participants in the navigator arm underwent a baseline interview using a strengths-based case management approach to assist in identifying barriers to entering care and devising solutions to best cope with perceived barriers. Over 4 months, participants in the navigator arm received scheduled phone and text messages. The primary outcome of the study is linkage and retention in care, assessed 9 months after enrollment. For ART-eligible participants without TB, the primary outcome is 3 months on ART as documented in the medical record; participants co-infected with TB are also eligible to meet the primary outcome of completion of 6 months of TB treatment, as documented by the TB clinic. Secondary outcomes include mortality, receipt of CD4 count and TB test results, and repeat CD4 counts for those not ART-eligible at baseline. We hypothesize that a health system navigator can help identify and positively affect modifiable patient factors, including self-efficacy and social support, that in turn can improve linkage to and retention in HIV and TB care. Discussion We are currently evaluating the clinical impact of a novel health system navigator intervention to promote entry to and retention in HIV and TB care for people newly diagnosed with HIV. The details of this study protocol will inform clinicians, investigators, and policy makers of strategies to best support HIV-infected patients in resource-limited settings. Trial registration Clinicaltrials.gov. unique identifier: NCT01188941

Assessing rates and contextual predictors of 5-year mortality among HIV-infected and HIV-uninfected individuals following HIV testing in Durban, South Africa

Abstract Background Little is known about contextual factors that predict long-term mortality following HIV testing in resource-limited settings. We evaluated the impact of contextual factors on 5-year mortality among HIV-infected and HIV-uninfected individuals in Durban, South Africa. Methods We used data from the Sizanani trial (NCT01188941) in which adults (≥18y) were enrolled prior to HIV testing at 4 outpatient sites. We ascertained vital status via the South African National Population Register. We used random survival forests to identify the most influential predictors of time to death and incorporated these into a Cox model that included age, gender, HIV status, CD4 count, healthcare usage, health facility type, mental health, and self-identified barriers to care (i.e., service delivery, financial, logistical, structural and perceived health). Results Among 4816 participants, 39% were HIV-infected. Median age was 31y and 49% were female. 380 of 2508 with survival information (15%) died during median follow-up of 5.8y. For both HIV-infected and HIV-uninfected participants, each additional barrier domain increased the HR of dying by 11% (HR 1.11, 95% CI 1.05–1.18). Every 10-point increase in mental health score decreased the HR by 7% (HR 0.93, 95% CI 0.89–0.97). The hazard ratio (HR) for death of HIV-infected versus HIV-uninfected varied by age: HR of 6.59 (95% CI: 4.79–9.06) at age 20 dropping to a HR of 1.13 (95% CI: 0.86–1.48) at age 60. Conclusions Independent of serostatus, more self-identified barrier domains and poorer mental health increased mortality risk. Additionally, the impact of HIV on mortality was most pronounced in younger persons. These factors may be used to identify high-risk individuals requiring intensive follow up, regardless of serostatus. Trial registration Clinical Trials.gov Identifier NCT01188941. Registered 26 August 2010

Incidence of Postpartum Infection, Outcomes and Associated Risk Factors at Mbarara Regional Referral Hospital in Uganda

Background: There is a paucity of recent prospective data on the incidence of postpartum infections and associated risk factors in sub-Saharan Africa. Retrospective studies estimate that puerperal sepsis causes approximately 10% of maternal deaths in Africa. Methods: We enrolled 4231 women presenting to a Ugandan regional referral hospital for delivery or postpartum care into a prospective cohort and measured vital signs postpartum. Women developing fever (\u3e 38.0 °C) or hypothermia (\u3c 36.0 °C) underwent symptom questionnaire, structured physical exam, malaria testing, blood, and urine cultures. Demographic, treatment, and post-discharge outcomes data were collected from febrile/hypothermic women and a random sample of 1708 normothermic women. The primary outcome was in-hospital postpartum infection. Multivariable logistic regression was used to determine factors independently associated with postpartum fever/ hypothermia and with confirmed infection. Results: Overall, 4176/4231 (99%) had ≥1 temperature measured and 205/4231 (5%) were febrile or hypothermic. An additional 1708 normothermic women were randomly selected for additional data collection, for a total sample size of 1913 participants, 1730 (90%) of whom had complete data. The mean age was 25 years, 214 (12%) were HIV-infected, 874 (51%) delivered by cesarean and 662 (38%) were primigravidae. Among febrile/hypothermic participants, 174/205 (85%) underwent full clinical and microbiological evaluation for infection, and an additional 24 (12%) had a partial evaluation. Overall, 84/4231 (2%) of participants met criteria for one or more in-hospital postpartum infections. Endometritis was the most common, identified in 76/193 (39%) of women evaluated clinically. Twenty-five of 175 (14%) participants with urinalysis and urine culture results met criteria for urinary tract infection. Bloodstream infection was diagnosed in 5/185 (3%) participants with blood culture results. Another 5/186 (3%) tested positive for malaria. Cesarean delivery was independently associated with incident, in-hospital postpartum infection (aOR 3.9, 95% CI 1.5– 10.3, P = 0.006), while antenatal clinic attendance was associated with reduced odds (aOR 0.4, 95% CI 0.2–0.9, P = 0.02). There was no difference in in-hospital maternal deaths between the febrile/hypothermic (1, 0.5%) and normothermic groups (0, P = 0.11)

High rates of unplanned interruptions from HIV care early after antiretroviral therapy initiation in Nigeria

Background: Unplanned care interruption (UCI) challenges effective HIV treatment. We determined the frequency and risk factors for UCI in Nigeria. Methods: We conducted a retrospective-cohort study of adults initiating antiretroviral therapy (ART) between January 2009 and December 2011. At censor, patients were defined as in care, UCI, or inactive. Associations between baseline factors and UCI rates were quantified using Poisson regression. Results: Among 2,496 patients, 44 % remained in care, 35 % had ≥1 UCI, and 21 % became inactive. UCI rates were higher in the first year on ART (39/100PY), than the second (19/100PY), third (16/100PY), and fourth (14/100PY) years (p 350/uL (IRR 3.21, p 1,000 copies/ml upon return to care. Discussion UCI were observed in over one-third of patients treated, and were most common in the first year on ART. High baseline CD4 count at ART initiation was the greatest predictor of subsequent UCI. Conclusions: Interventions focused on the first year on ART are needed to improve continuity of HIV care