Is laboratory screening prior to antiretroviral treatment useful in Johannesburg, South Africa? Baseline findings of a clinical trial.

BACKGROUND: Screening for renal, hepatic and haematological disorders complicates the initiation of current first-line antiretroviral therapy (ART). Each additional test done adds substantial costs, both through direct laboratory expenses, but also by increasing the burden on health workers and patients. Evaluating the prevalence of clinically relevant abnormalities in different population groups could guide decisions about what tests to recommend in national guidelines, or in local adaptations of these. METHODS: As part of enrolment procedures in a clinical trial, 771 HIV-positive adults, predominantly from inner-city primary health care clinics, underwent laboratory screening prior to ART. Participants had to be eligible for ART, based on the then CD4 eligibility threshold of 350 cells/µL, antiretroviral naïve and have no symptoms of peripheral neuropathy. RESULTS: Participants were mostly female (57%) and a mean 34 years old. Creatinine clearance rates were almost all above 50 mL/min (99%), although 5% had microalbuminuria. Hepatitis B antigenaemia was common (8% of participants), of whom 40% had a raised AST/ALT, though only 2 had transaminase levels above 200 IU/L. Only 2% of participants had severe anaemia (haemoglobin <8 g/dl) and 1% neutropaenia (neutrophils <0.75 × 10^9/L). Costs per case detected of hepatitis B infection was USD135, but more than USD800 for a raised creatinine. CONCLUSIONS: Hepatitis B continues to be a common co-infection in HIV-infected adults, and adds complexity to management of ART switches involving tenofovir. Routine renal and haematological screening prior to ART detected few abnormalities. The use of these screening tests should be assessed among patients with higher CD4 counts, who may even have fewer abnormalities. Formal evaluation of cost-effectiveness of laboratory screening prior to ART is warranted.

Implementation of an mHealth App to Promote Engagement During HIV Care and Viral Load Suppression in Johannesburg, South Africa (iThemba Life): Pilot Technical Feasibility and Acceptability Study.

BACKGROUND: South Africa has the largest HIV treatment program worldwide. Retention in care and medication adherence remain problematic necessitating innovative solutions for improving HIV care. The increasing availability and use of mobile technology can support positive clinical outcomes for persons living with HIV. iThemba Life is a mobile health app designed with input from South African health professionals and patients, promoting engagement with HIV care through access to medical results. OBJECTIVE: This study aimed to test the feasibility and acceptability of receiving HIV viral load (VL) results through the app and compare the time to HIV VL result return for study participants before and after app use. METHODS: Using convenience sampling, adults having routine VL phlebotomy were recruited from 2 Johannesburg health facilities. After signed consent, the app was downloaded on their Android smartphones, phlebotomy was performed, and the sample barcode was scanned through their phone to link the sample and app. Participants received a notification of the result availability and logged into the app to view results, their explanation and recommended action. RESULTS: Overall, 750 people were screened to enroll 500 participants. Of 750, 113 (15.1%) failed eligibility screening. 21.5% (137/637) had smartphone technical limitations preventing enrollment. Results were released to 92.2% (461/500) of participants' phones. App technical issues and laboratory operational issues limited the number of released results. Approximately 78.1% (360/461) results were viewed in the app. Median time from notification of availability to result viewed being 15.5 hours (0.6; range 0-150 days). Turnaround time from phlebotomy to the result being received was 6 (range 1-167) days for users versus 56 days (range 10-430 days; P<.001) before app use. Overall, 4% (20/500) of participants received unsuppressed results (VL>1000 copies/mL). Turnaround time for unsuppressed results was 7 days for participants versus 37.5 days before app use (P<.001). The difference before and after app use in the suppressed and unsuppressed users for time from sample collection to result delivery was statistically significant. Of 20 participants, 12 (60%) returned for a confirmatory VL during the study period. The time from an unsuppressed VL to a confirmatory VL was 106 days for app users versus 203 days before app use (P<.001). Overall, 52.4% (262/500) of participants completed an exit survey; 23.2% (58/250) reported challenges in viewing their VL results. Moreover, 58% (35/60) reported that they overcame challenges with technical assistance from others, and 97.3% (255/262) wanted to continue using the app for VL results. CONCLUSIONS: Using iThemba Life for VL results was well-received despite limited smartphone access for some participants. App users received results 10 times sooner than before the app and 5 times sooner if their VL >1000 copies/mL. This increased notification speed led to participants wanting to continue using iThemba Life.

Low-dose ritonavir-boosted darunavir once daily versus ritonavir-boosted lopinavir for participants with less than 50 HIV RNA copies per mL (WRHI 052): a randomised, open-label, phase 3, non-inferiority trial.

BACKGROUND: Pilot studies suggest that ritonavir-boosted darunavir could show high efficacy at doses below those currently approved. We investigated whether switch to 400 mg of darunavir boosted with 100 mg ritonavir once daily could show equivalent efficacy to continuation of ritonavir-boosted lopinavir (a protease inhibitor commonly used in low-income and middle-income countries) for individuals with HIV RNA suppression. METHODS: In the WRHI 052 study, a randomised, parallel-group, open-label, non-inferiority phase 3 trial, adults who were HIV-1 positive were enrolled in Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa. Eligible participants were 18 years or older, who tolerated ritonavir-boosted lopinavir in combination with two nucleoside analogues (standard of care) for 6 months or more, and had plasma HIV-1 RNA of less than 50 copies per mL within 60 days of enrolment. We randomly assigned participants (1:1), using a computer-generated randomisation plan, to switch to darunavir (400 mg) boosted with ritonavir (100 mg) once daily or remain on ritonavir-boosted lopinavir (800 mg [plus 200 mg ritonavir]), with nucleoside analogues left unchanged. The primary endpoint was the proportion of patients with less than 50 HIV-1 RNA copies per mL at week 48 (US Food and Drug Administration snapshot algorithm; non-inferiority margin -4%). Primary and safety analyses included participants receiving at least one dose of darunavir boosted with ritonavir. This trial is registered with ClinicalTrials.gov, number NCT02671383. FINDINGS: Between June 30, 2016, and June 15, 2017, 148 participants were assigned to ritonavir-boosted darunavir 400 mg and 152 continued on their lopinavir-containing regimen. Four (3%) patients in the darunavir group and three (2%) in the lopinavir group discontinued before week 48. At week 48, darunavir was non-inferior to lopinavir for the primary outcome (142 [96%] of 148 participants on darunavir had <50 HIV-1 RNA copies per mL vs 143 [94%] of 152 participants on lopinavir; difference 1·9% [95% CI -3·4 to 7·3]), with a predefined margin of -4%. More participants taking darunavir (30 [20%] participants) had drug-related adverse events than those on lopinavir (eight [5%]), but the adverse events were generally asymptomatic and resolved when switching back to lopinavir. Elevated liver transaminase in three (1%; one symptomatic) darunavir participants led to study withdrawal; all transaminase elevations resolved on restarting lopinavir. INTERPRETATION: Low-dose ritonavir-boosted darunavir might be a safe and efficacious switch option to maintain HIV suppression for patients on lopinavir. However, an adequately powered and designed study in viraemic participants is needed. FUNDING: South African Medical Research Council, United States Agency for International Development, and US National Institute of Allergy and Infectious Diseases.

CD4 cell count variability with repeat testing in South Africa: Should reporting include both absolute counts and ranges of plausible values?

Although eligibility for antiretroviral treatment is no longer based on CD4 thresholds, CD4 testing remains important. Variation in CD4 cell count complicates initiation of antibiotic prophylaxis, differential diagnoses and assessments of immunological recovery. Five hundred and fifty-three HIV-positive antiretroviral-naïve adults, recruited from inner-city clinics, had three serial CD4 cell count tests. Test 1 was mostly done in a laboratory network supporting primary care clinics, while Tests 2 and 3 were performed in a tertiary-level laboratory. Reproducibility was assessed through Bland-Altman limits of agreement and coefficients of variation. Participants, a mean age of 34 years and mostly female (57%), had a median 203 CD4 cells/µL (Test 1). Seventeen per cent classified as having advanced HIV disease (CD4 cell count < 200 cells/µL) on Test 1 had a CD4 cell count > 200 cells/µL on Tests 2 and 3. Mean differences between tests were <10 cells/µL for all comparisons. Limits of agreement for Tests 1 and 2 were -106.9 to 112.7 and coefficient of variation 15. Corresponding figures for Tests 2 and 3 were -88.2 to 103.4, and 13. Means of tests were similar, suggesting no systematic measurement differences, despite testing being done at different times. Variations were, however, considerable in many instances, though smaller in testing done in the same laboratory. CD4 cut-offs must not be applied rigidly, but rather constitute one amongst many factors used to guide patient care. Moreover, given the difficulties in determining whether CD4 changes are due to HIV disease, or other biological and laboratory factors, CD4 laboratory reports should include a range of plausible values, not only the absolute count.