Ingrid V. Bassett

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.

Diagnostic point-of-care tests in resource-limited settings

The aim of diagnostic point-of-care testing is to minimise the time to obtain a test result, thereby allowing clinicians and patients to make a quick clinical decision. Because point-of-care tests are used in resource-limited settings, the benefits need to outweigh the costs. To optimise point-of-care testing in resource-limited settings, diagnostic tests need rigorous assessments focused on relevant clinical outcomes and operational costs, which differ from assessments of conventional diagnostic tests. We reviewed published studies on point-of-care testing in resource-limited settings, and found no clearly defined metric for the clinical usefulness of point-of-care testing. Therefore, we propose a framework for the assessment of point-of-care tests, and suggest and define the term test efficacy to describe the ability of a diagnostic test to support a clinical decision within its operational context. We also propose revised criteria for an ideal diagnostic point-of-care test in resource-limited settings. Through systematic assessments, comparisons between centralised testing and novel point-of-care technologies can be more formalised, and health officials can better establish which point-of-care technologies represent valuable additions to their clinical programmes.

Loss to Care and Death Before Antiretroviral Therapy in Durban, South Africa

Objective:To examine the loss to care and mortality rates before starting antiretroviral therapy (ART) among ART eligible HIV-infected patients in Durban, South Africa. Design:Retrospective cohort study. Methods:We reviewed data from ART eligible adults (≥18 years) at an urban HIV clinic that charges a monthly fee from July to December 2006. ART eligibility was based on CD4 count ≤200 cells per microliter or clinical criteria and a psychosocial assessment. Patients who did not start ART and were lost within 3 months were phoned. Correlates of loss to care were evaluated using logistic regression. Results:During the study period, 501 patients registered for ART training. Mean time from initial CD4 count to first ART training was 3.6 months (interquartile range 2.3-3.9 months). Four hundred eight patients (81.4%) were in care and on ART at 3-month follow-up, and 11 (2.2%) were in care but had not initiated ART. Eighty-two ART eligible patients (16.4%) were lost before ART initiation. Of these, 28 (34.1%) had died; two thirds of deaths occurred before or within 2 months after the first ART training. Despite multiple attempts, 32 patients (39%) were unreachable by phone. Lower baseline CD4 counts (≤100 cells/μL) and unemployment were independently associated with being lost. Conclusions:Loss to care and death occur frequently before starting ART at an HIV clinic in Durban, South Africa. This delay from CD4 count to ART training, even among those with the lowest CD4 counts, highlights the need for interventions that improve linkage to care and prioritize ART initiation for those with low baseline CD4 counts.

Who starts antiretroviral therapy in Durban, South Africa?… not everyone who should

Objective:To evaluate rates of antiretroviral therapy (ART) initiation within 12 months of a new HIV diagnosis in Durban, South Africa. Design:Prospective observational cohort. Methods:Adults (≥18 years) were enrolled before HIV testing at two outpatient clinics into the South African Test, Identify and Link cohort. Both sites offer comprehensive HIV care. HIV test results, CD4 cell counts, dates of ART initiation and dates of death were collected from medical records and 12-month patient/family interviews were conducted. ART eligibility was defined as a CD4 cell count less than 200 cells/μl within 90 days of HIV diagnosis. The primary endpoint was ART initiation within 12 months for ART-eligible subjects. Results:From November 2006 to October 2008, 1474 newly diagnosed HIV-infected outpatients were enrolled, 1012 (69%) of whom underwent CD4 cell count testing within 90 days. The median CD4 cell count was 159 cells/μl (interquartile range 65–299). Of those who underwent CD4 cell count testing, 538 (53%) were ART-eligible. Only 210 (39%) eligible enrollees were known to have initiated ART within 12 months. Among ART-eligible subjects, there were 108 known deaths; 82% occurred before ART initiation or with unknown ART initiation status. Men [rate ratio (RR) 1.3, 95% confidence interval (CI) 1.1–1.5] and subjects without an HIV-infected family member/friend (RR 1.3, 95% CI 1.1–1.7) were more likely not to start ART. Conclusion:Less than half of ART-eligible subjects started ART within 12 months. Substantial attrition and mortality follow HIV diagnosis before ART initiation in Durban, South Africa. Major efforts directed towards earlier HIV diagnosis, effective linkage to care and timely ART initiation are urgently needed.

Trends in CD4 Count at Presentation to Care and Treatment Initiation in Sub-Saharan Africa, 2002–2013: A Meta-analysis

BACKGROUND Both population- and individual-level benefits of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) are contingent on early diagnosis and initiation of therapy. We estimated trends in disease status at presentation to care and at ART initiation in sub-Saharan Africa. METHODS We searched PubMed for studies published January 2002-December 2013 that reported CD4 cell count at presentation or ART initiation among adults in sub-Saharan Africa. We abstracted study sample size, year(s), and mean CD4 count. A random-effects meta-regression model was used to obtain pooled estimates during each year of the observation period. RESULTS We identified 56 articles reporting CD4 count at presentation (N = 295 455) and 71 articles reporting CD4 count at ART initiation (N = 549 702). The mean estimated CD4 count in 2002 was 251 cells/µL at presentation and 152 cells/µL at ART initiation. During 2002-2013, neither CD4 count at presentation (β = 5.8 cells/year; 95% confidence interval [CI], -10.7 to 22.4 cells/year), nor CD4 count at ART initiation (β = -1.1 cells/year; 95% CI, -8.4 to 6.2 cells/year) increased significantly. Excluding studies of opportunistic infections or prevention of mother-to-child transmission did not alter our findings. Among studies conducted in South Africa (N = 14), CD4 count at presentation increased by 39.9 cells/year (95% CI, 9.2-70.2 cells/year; P = .02), but CD4 count at ART initiation did not change. CONCLUSIONS CD4 counts at presentation to care and at ART initiation in sub-Saharan Africa have not increased over the past decade. Barriers to presentation, diagnosis, and linkage to HIV care remain major challenges that require attention to optimize population-level benefits of ART.

Routine voluntary HIV testing in Durban, South Africa : The experience from an outpatient department

Objective:To evaluate the yield of a routine voluntary HIV testing program compared with traditional provider-referred voluntary counseling and testing (VCT) in a hospital-affiliated outpatient department (OPD) in Durban, South Africa. Design and Methods:In a prospective 14-week “standard of care” period, we compared OPD physician logs documenting patient referrals to the hospital VCT site with HIV test registers to measure patient completion of HIV test referral. The standard of care period was followed by a 12-week intervention during which all patients who registered at the OPD were given an educational intervention and offered a rapid HIV test at no charge as part of routine care. Results:During the standard of care period, OPD physicians referred 435 patients aged ≥18 years for HIV testing; 137 (31.5%) of the referred patients completed testing at the VCT site within 4 weeks. Among those tested, 102 (74.5%) were HIV infected. During the intervention period, 1414 adults accepted HIV testing and 1498 declined. Of those tested, 463 (32.7%, 95% confidence interval: 30.3 to 35.3) were HIV infected. Routine HIV testing in the OPD identified 39 new HIV cases per week compared with 8 new cases per week with standard of care testing based on physician referral to a VCT site (P < 0.0001). Conclusions:Routine voluntary HIV testing in an OPD in South Africa leads to significantly higher rates of detection of HIV disease. This strategy should be implemented more widely in high HIV prevalence areas where treatment is available.

Effectiveness of pediatric antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis.

BACKGROUND Responses to antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected children in resource-limited settings have recently been reported, but outcomes vary. We sought to derive pooled estimates of the 12-month rate of virologic suppression (HIV RNA, <400 copies/mL) and gain in CD4 cell percentage (DeltaCD4%) for children initiating ART in resource-limited settings. METHODS We conducted a systematic review and meta-analysis of published reports of HIV RNA and CD4 outcomes for treatment-naive children aged 0-17 years old by means of the Medline, EMBASE (Excerpta Medica Database), and LILACS (Latin American and Caribbean Health Sciences Literature) electronic databases and the Cochrane Clinical Trials Register. Pooled estimates of the reported proportion with HIV RNA <400 copies/mL and DeltaCD4% after 12 months of ART were derived using patient-level estimates and fixed- and random-effects models. To approximate intention-to-treat analyses, in sensitivity analyses children with missing 12-month data were assumed to have HIV RNA>400 copies/mL or DeltaCD4% of zero. RESULTS In patient-level estimates after 12 months of ART, the pooled proportion with virologic suppression was 70% (95% confidence interval [CI], 67%-73%); the pooled DeltaCD4% was 13.7% (95% CI, 11.8%-15.7%). Results from the fixed- and random-effects models were similar. In approximated intention-to-treat analyses, the pooled estimates decreased to 53% with virologic suppression (95% CI, 50%-55%) and to a DeltaCD4% of 8.5% (95% CI, 5.5%-11.4%). CONCLUSIONS Pooled estimates of reported virologic and immunologic benefits after 12 months of ART among HIV-infected children in resource-limited settings are comparable with those observed among children in developed settings. Consistency in reporting on reasons for missing data will aid in the evaluation of ART outcomes in resource-limited settings.

Two Drugs or Three? Balancing Efficacy, Toxicity, and Resistance in Postexposure Prophylaxis for Occupational Exposure to HIV

Thousands of health care workers are potentially exposed to human immunodeficiency virus (HIV) each year via occupationally acquired needlesticks. The Centers for Disease Control and Prevention (Atlanta, GA) advise health care workers who experience a high-risk occupational exposure from an HIV-infected patient to begin receiving multidrug antiretroviral postexposure prophylaxis (PEP) as soon as possible, preferably within 36 h after exposure. Although the need to prescribe antiretroviral postexposure prophylaxis in a timely fashion is common, few data exist regarding the efficacy and optimal regimen for prophylaxis to prevent transmission. Our objectives were to examine the limited human and animal data on postexposure prophylaxis, to elucidate the factors that affect the choice of 2 versus 3 drugs as the optimal prophylactic drug regimen, and to place these findings within a mathematical framework to help guide the prescription of PEP.

Integrating HIV Screening into Routine Health Care in Resource-Limited Settings

The United Nations is committed to achieving universal access to human immunodeficiency virus (HIV) care, treatment, and prevention. Although the gateway to HIV care and secondary prevention is knowledge of serostatus, use of voluntary counseling and testing in resource-limited settings with the highest burden of HIV infection and AIDS has been limited. On the basis of evidence of increased patient uptake and the opportunity to avoid missed HIV testing opportunities in health care facilities, in 2007, the World Health Organization recommended provider-initiated HIV testing as a standard part of medical care in settings with generalized HIV epidemics. Although provider-initiated testing has shown promise, optimal implementation strategies that ensure broad coverage, while preserving human rights, remain an active area of research. We review the benefits of knowledge of HIV serostatus and evidence from multiple countries surrounding the successes and pitfalls of provider-initiated testing in health care and home-based settings.

The clinical impact and cost-effectiveness of routine, voluntary HIV screening in South Africa.

Background:Although 900,000 HIV-infected South Africans receive antiretroviral therapy, the majority of South Africans with HIV remain undiagnosed. Methods:We use a published simulation model of HIV case detection and treatment to examine 3 HIV screening scenarios, in addition to current practice as follows: (1) one-time; (2) every 5 years; and (3) annually. South African model input data include the following: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of