Same-day antiretroviral therapy initiation for HIV-infected adults in South Africa: Analysis of routine data.

Same-day initiation (SDI) of antiretroviral therapy (ART) has been recommended to improve ART programme outcomes in South Africa since August 2017. This study assessed implementation of SDI over time in two South African districts, describing the characteristics of same-day initiators and evaluating the impact of SDI on retention in ART care. Routine data were analysed for HIV-infected adults who were newly initiating ART in Johannesburg or Mopani Districts between October 2017 and June 2018. Characteristics of same-day ART initiators were compared to later initiators, and losses to follow-up (LTFU) to six months were assessed using Kaplan Meier survival analysis and multivariate logistic regression. The dataset comprised 32 290 records (29 964 from Johannesburg and 2 326 from Mopani). The overall rate of SDI was 40.4% (n = 13 038), increasing from 30.3% in October 2017 to 54.2% in June 2018. Same-day ART initiators were younger, more likely to be female and presented with less advanced clinical disease than those initiating treatment at later times following diagnosis (p<0.001 for all). SDI was associated with disengagement from care: LTFU was 30.1% in the SDI group compared to 22.4%, 19.8% and 21.9% among clients initiating ART 1-7 days, 8-21 days and ≥22 days after HIV diagnosis, respectively (p<0.001). LTFU was significantly more likely among clients in Johannesburg versus Mopani (adjusted odds ratio (aOR) = 1.43, p<0.001) and among same-day versus later initiators (aOR = 1.45, p<0.001), while increasing age reduced LTFU (aOR = 0.97, p<0.001). In conclusion, SDI has increased over time as per national guidelines, but there is serious concern regarding the reduced rate of retention among same-day initiators. Nevertheless, SDI may result in a net programmatic benefit provided that interventions are implemented to support client readiness for treatment and ongoing engagement in ART care, particularly among younger adults in large ART programmes such as Johannesburg.

CD4 testing after initiation of antiretroviral therapy: Analysis of routine data from the South African HIV programme.

BACKGROUND: People living with HIV (PLHIV) who have low CD4 counts require advanced clinical care (ACC) to minimise morbidity and mortality risk. These patients include immunological non-responders (INRs) with low CD4 counts despite a suppressed viral load. OBJECTIVES: To determine the proportion of patients with low CD4 counts after antiretroviral therapy (ART) initiation and to describe INRs within that group. METHODS: Routine Three Interlinked Electronic Registers.Net (TIER.Net) data from four South African districts were analysed for adult PLHIV on ART > 12 months. Immunological non-responders were defined as patients on ART > 4 years who were virally suppressed (viral load < 1000 copies/mL) with a CD4 count ≤ 350 cell/mm3. RESULTS: Baseline CD4 was recorded for 80.9% of the 869 571 patients newly initiating ART, with 37.2% of those starting ART since 2017 having baseline counts ≤ 200 cells/mm3. Amongst all 1 178 190 patients on ART, only 46.5% had a CD4 test after ART initiation and of these, 14.3% had CD4 ≤ 200 cells/mm3. This proportion was highest amongst patients on ART ≤ 2 years (19.7%) (p < 0.001). Amongst virally suppressed patients, 20.0% were INRs. Immunological non-response was significantly more likely amongst patients on second-line ART (adjusted odds ratio [aOR] 1.79), those aged 35-45 and ≥ 45 years (aOR 1.15 and 1.50, respectively), males (aOR 2.28) and patients with confirmed TB (aOR 2.49), and was significantly less likely in cases with higher baseline CD4 count (aOR 0.35). CONCLUSION: CD4 testing subsequent to ART initiation is poorly implemented and there is a notable proportion of patients with low CD4 counts. Guidelines regarding CD4 testing and ACC need to be more widely implemented to identify patients with low CD4 counts and improve their outcomes.

Baseline CD4 and mortality trends in the South African human immunodeficiency virus programme: Analysis of routine data.

BACKGROUND: Despite widespread availability of antiretroviral therapy (ART) in South Africa, there remains a considerable burden of human immunodeficiency virus (HIV)-related morbidity and mortality. OBJECTIVES: To describe ART initiation and outcome trends over time, with a focus on clients presenting with advanced HIV-infection, so as to identify interventions to reduce morbidity and mortality. METHODS: Routine TIER.Net data from HIV-infected adults who had a documented baseline CD4 count and were newly initiating ART in Johannesburg or Mopani districts from 2004 to 2017 were analysed. Trends in baseline CD4 count and 5-year mortality were investigated and the population initiating ART with CD4 < 200 cells/mm3 was described. RESULTS: The Johannesburg and Mopani data sets comprised 203 131 and 101 814 records, respectively. Although median CD4 count increased over time, the proportion of initiations at CD4 < 200 cells/mm3 in 2017 remained high (Johannesburg 39%, Mopani 35%). Mortality was significantly increased among clients with CD4 < 200 compared to those with higher baseline counts (p < 0.001). Even though mortality among clients with low CD4 declined over time, likely because of improved drug regimens, in 2016-2017 mortality was still significantly increased among these clients (p < 0.001). Delivery of cotrimoxazole prophylaxis to clients with low CD4 declined over time to < 30% in 2017 and was associated with clinical stage. Presentation with CD4 < 200 cells/mm3 was associated with older age, male gender and hospitalisation. CONCLUSION: A concerningly large proportion of South Africans still initiate ART at low CD4 counts. This is associated with increased mortality and requires targeted interventions to improve delivery of prophylactic regimens and early engagement in care.

Strengthening primary eye care in South Africa: An assessment of services and prospective evaluation of a health systems support package.

Visual impairment is a significant public health concern, particularly in low- and middle-income countries where eye care is predominantly provided at the primary healthcare (PHC) level, known as primary eye care. This study aimed to perform an evaluation of primary eye care services in three districts of South Africa and to assess whether an ophthalmic health system strengthening (HSS) package could improve these services. Baseline surveys were conducted in Cape Winelands District, Johannesburg Health District and Mopani District at 14, 25 and 36 PHC facilities, respectively. Thereafter, the HSS package, comprising group training, individual mentoring, stakeholder engagement and resource provision, was implemented in 20 intervention sites in Mopani District, with the remaining 16 Mopani facilities serving as control sites. At baseline, less than half the facilities in Johannesburg and Mopani had dedicated eye care personnel or sufficient space to measure visual acuity. Although visual acuity charts were available in most facilities, <50% assessed patients at the correct distance. Median score for availability of nine essential drugs was <70%. Referral criteria knowledge was highest in Cape Winelands and Johannesburg, with poor clinical knowledge across all districts. Several HSS interventions produced successful outcomes: compared to control sites there was a significant increase in the proportion of intervention sites with eye care personnel and resources such as visual acuity charts (p = 0.02 and <0.01, respectively). However, engaging with district pharmacists did not improve availability of essential drugs (p = 0.47). Referral criteria knowledge improved significantly in intervention sites (p<0.01) but there was no improvement in clinical knowledge (p = 0.76). Primary eye care in South Africa faces multiple challenges with regard to organisation of care, resource availability and clinical competence. The HSS package successfully improved some aspects of this care, but further development is warranted together with debate regarding the positioning of eye services at PHC level.

A mathematical model evaluating the timing of early diagnostic testing in HIV-exposed infants in South Africa.

BACKGROUND: Antiretroviral therapy is often initiated too late to impact early HIV-related infant mortality. Earlier treatment requires an earlier diagnosis, and the currently recommended 6-week HIV polymerase chain reaction (PCR) test needs reconsideration. This study aims to identify (1) optimal testing intervals to maximize the number of perinatal HIV infections diagnosed and (2) programmatic issues that impact diagnosis. METHODS: A mathematical model was developed to simulate antiretroviral prophylaxis uptake and health outcomes in 240,000 HIV-exposed South African infants. The model considered routine early testing with 1 PCR (at birth, 6, 10, or 14 weeks of age) and with 2 PCR tests (at birth and at 6, 10, or 14 weeks of age). RESULTS: A single 6-week test would diagnose the same number of perinatal HIV infections as birth testing (P = 0.92) but fewer infections than a 10-week test (P < 0.01). Ten-week testing identifies the highest number of perinatally infected infants (P < 0.01 compared with a single test at all other ages) but does not save additional life years compared with birth testing (P = 0.27). Performing 2 PCR tests (at birth and 10 weeks) would identify the highest number of perinatal infections (P < 0.01 versus a second 6- or 14-week test). However, 25% of perinatal HIV infections would remain undiagnosed, largely because of failure to return PCR test results to caregivers. CONCLUSIONS: Six weeks may no longer be the optimal age to diagnose perinatal HIV infections. Two early PCR tests (at birth and 10 weeks) would likely be the ideal diagnostic algorithm, but must be coupled with improved program coverage.

Birth diagnosis of HIV infection in infants to reduce infant mortality and monitor for elimination of mother-to-child transmission.

BACKGROUND: Early initiation of antiretroviral therapy depends on an early infant diagnosis and is critical to reduce HIV-related infant mortality. We describe the implementation of a routine prevention of mother-to-child transmission program and focus on early infant diagnosis to identify opportunities to improve outcomes. METHODS: HIV-exposed infants and their mothers were enrolled in a prospective, observational cohort study at a routine, hospital-based prevention of mother-to-child transmission and HIV treatment service in Johannesburg, South Africa. Infant HIV status was determined by testing samples collected between birth and 6 weeks and searching the national laboratory information system for polymerase chain reaction results of defaulting infants who accessed testing elsewhere. RESULTS: Of 838 enrolled infants, HIV status was determined for 606 (72.3%) by testing at the study site, 85 (10.1%) by accessing test results from other facilities, 19 (2.3%) by testing stored samples and remained unknown in 128 (15.3%) infants. In total, 38 perinatally HIV-infected infants were identified. Thirty (79%) HIV-infected infants accessed 6-week testing and initiated antiretroviral therapy at a median age of 16.0 weeks, but only 14 were in care a median of 68 weeks later and 4 had died. Eight (21%) HIV-infected infants, 2 of whom died, escaped identification by routine testing. Their mothers were younger, more likely to be foreign and accessed less optimal antenatal care. CONCLUSIONS: Six-week testing delayed antiretroviral therapy initiation beyond the time of early HIV-related infant mortality and missed one-fifth of perinatally HIV-infected infants. Earlier diagnosis and improved retention in care are required to reduce infant mortality and accurately measure elimination of mother-to-child transmission.

Early diagnosis of in utero and intrapartum HIV infection in infants prior to 6 weeks of age.

Early initiation of antiretroviral therapy reduces HIV-related infant mortality. The early peak of pediatric HIV-related deaths in South Africa occurs at 3 months of age, coinciding with the earliest age at which treatment is initiated following PCR testing at 6 weeks of age. Earlier diagnosis is necessary to reduce infant mortality. The performances of the Amplicor DNA PCR, COBAS AmpliPrep/COBAS TaqMan (CAP/CTM), and Aptima assays for detecting early HIV infection (acquired in utero and intrapartum) up to 6 weeks of age were compared. Dried blood spots (DBS) were collected at birth and at 2, 4, and 6 weeks from HIV-exposed infants enrolled in an observational cohort study in Johannesburg, South Africa. HIV status was determined at 6 weeks by DNA PCR on whole blood. Serial DBS samples from all HIV-infected infants and two HIV-uninfected, age-matched controls were tested with the 3 assays. Of 710 infants of known HIV status, 38 (5.4%) had in utero (n = 29) or intrapartum (n = 9) infections. By 14 weeks, when treatment should have been initiated, 13 (45%) in utero-infected and 2 (22%) intrapartum-infected infants had died or were lost to follow-up. The CAP/CTM and Aptima assays identified 76.3% of all infants with early HIV infections at birth and by 4 weeks were 96% sensitive. DNA PCR demonstrated lower sensitivities at birth and 4 weeks of 68.4% and 87.5%, respectively. All assays had the lowest sensitivity at 2 weeks of age. CAP/CTM was the only assay with 100% specificity at all ages. Testing at birth versus 6 weeks of age identifies a higher total number of HIV-infected infants, irrespective of the assay.

The performance of 5 rapid HIV tests using whole blood in infants and children: selecting a test to achieve the clinical objective.

BACKGROUND: Rapid tests have the potential to improve the identification of HIV-infected children in resource-limited settings. However, they remain underutilized because of a lack of data on their performance in the field using whole blood specimens. This study aimed to assess the accuracy of rapid tests for detecting HIV exposure, excluding HIV infection in HIV-exposed infants, and diagnosing HIV infection in children older than 18 months of age. METHODS: Five rapid tests (First Response, Pareekshak, Determine, Smart Check, and Insti) were performed using whole blood from children enrolled in a multisite, cross-sectional study in South Africa. HIV enzyme-linked immunosorbent assay and DNA polymerase chain reaction results defined HIV exposure and infection, respectively, and were the standards used for comparison. RESULTS: Of the 851 children enrolled, 186 (21.9%) were infected with HIV. For detecting HIV exposure, Determine demonstrated the highest sensitivity of 99.3% (95% confidence interval, 98.0-99.8) in early infancy, but sensitivity declined with age as seroreversion occurred. After 8 months of age, all tests except First Response excluded HIV infection in 82% to 100% of HIV-uninfected infants and, in conjunction with a clinical assessment, did not miss any HIV-infected children. Insti was the only test that detected all HIV-infected infants, albeit on the smallest number of samples. The performance of all rapid tests in children older than 18 months of age was similar to that in adults. CONCLUSIONS: Determine was the only rapid test that had a high enough sensitivity for detecting HIV exposure in early infancy, but it identified seroreversion later in life than the other tests. Insti warrants further investigation for both indications.

Oral fluid tests for screening of human immunodeficiency virus-exposed infants.

In high human immunodeficiency virus (HIV) prevalence settings, routine screening of infants attending immunization visits could improve identification of HIV-exposed infants to receive an early diagnosis and appropriate interventions. This first assessment of 2 rapid oral fluid HIV tests in early infancy demonstrates a sensitivity of <90% for detection of HIV-exposure resulting in failure to detect at least 1 in 10 HIV-infected infants.