Initiating Antiretroviral Therapy for HIV at a Patient's First Clinic Visit: The RapIT Randomized Controlled Trial.

BACKGROUND: High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit. METHODS AND FINDINGS: RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study ("rapid arm") received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study ("standard arm") followed standard clinic procedures (three to five additional clinic visits over 2-4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 d. Three hundred and seventy-seven patients were enrolled in the study between May 8, 2013 and August 29, 2014 (median CD4 count 210 cells/mm3). In the rapid arm, 119/187 patients (64%) initiated treatment and were virally suppressed at 10 mo, compared to 96/190 (51%) in the standard arm (relative risk [RR] 1.26 [1.05-1.50]). In the rapid arm 182/187 (97%) initiated ART ≤90 d, compared to 136/190 (72%) in the standard arm (RR 1.36, 95% confidence interval [CI], 1.24-1.49). Among 318 patients who did initiate ART within 90 d, the hazard of attrition within the first 10 mo did not differ between the treatment arms (hazard ratio [HR] 1.06; 95% CI 0.61-1.84). The study was limited by the small number of sites and small sample size, and the generalizability of the results to other settings and to non-research conditions is uncertain. CONCLUSIONS: Offering single-visit ART initiation to adult patients in South Africa increased uptake of ART by 36% and viral suppression by 26%. This intervention should be considered for adoption in the public sector in Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT01710397, and South African National Clinical Trials Register DOH-27-0213-4177.

Correction: Initiating Antiretroviral Therapy for HIV at a Patient's First Clinic Visit: The RapIT Randomized Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pmed.1002015.].

A case-control study of risk factors for incident hepatitis B virus infection in South African blood donors.

OBJECTIVES: Hepatitis B virus (HBV) infection remains a global health problem. Risk factors for HBV infection are usually assessed in prevalent rather than incident infections. To identify demographic and behavioral risks associated with incident HBV among South African blood donors. METHODS: A case-control study was performed between November 2014 and January 2018. Cases were blood donors testing positive for HBV DNA with or without hepatitis B surface antigen but negative for antibody to hepatitis B core antigen. Participants completed an audio computer-assisted structured interview on exposures during the previous 6 months. Sex-specific multivariable logistic regression yielded independent associations between risks and HBV infection. RESULTS: 56 females and 37 males with incident HBV were compared to 438 female and 439 male controls, respectively. For females, risk factors were accepting money or goods for sex, using agents to prepare one's anus prior to anal sex, penetrating injury, non-Black race, and lower educational status. Men reporting homosexual or bisexual orientation or sex with other men, previous injury, referral for HBV testing, or lack of medical insurance were at increased risk. For both sexes, having more than two male sexual partners increased risk. CONCLUSIONS: Sexual behaviors predominated over parenteral exposures as risks for incident HBV in both female and male blood donors.

Blood Center Testing Allows the Detection and Rapid Treatment of Acute and Recent HIV Infection.

Blood donations in South Africa are tested for HIV RNA using individual donation NAT (ID-NAT), allowing detection and rapid antiretroviral therapy (ART) of acute HIV infections. We enrolled a cohort of acute and recent HIV-infected blood donation candidates in South Africa in 2015-2018, measured HIV antibody, ID-NAT, and recency of infection <195 days (Sedia LAg) at enrollment and initiated early ART. A small cohort of HIV elite controllers was followed without treatment. HIV reservoir measurements included ultrasensitive plasma RNA, cell-associated HIV RNA, and total DNA. Enrollment of 18 Fiebig I-III and 45 Fiebig IV-VI HIV clade C subjects occurred a median of 18 days after index blood donation. ART was administered successfully and compliance with follow-up visits was excellent. There were only minimal differences in HIV reservoir between ART initiation in Fiebig stages I-III vs. IV-VI, but ART noncompliance increased HIV reservoir. In 11 untreated HIV elite controllers, HIV reservoir levels were similar to or higher than those seen in our early treated cohort. National blood services can identify acute HIV cohorts for subsequent HIV cure research studies. Among HIV clade C-infected donors, HIV reservoir differed little by Fiebig stage at treatment initiation, but was smaller than in chronically treated HIV and those with ART noncompliance.

Estimates of prevalence of anti-SARS-CoV-2 antibodies among blood donors in eight provinces of South Africa in November 2021.

In line with previous instalments of analysis from this ongoing study to monitor 'Covid Seroprevalence' among blood donors in South Africa, we report on analysis of 3395 samples obtained from 8 to 12 November 2021 in all provinces of South Africa except the Western Cape. As in our previous analyses, we see no evidence of age and sex dependence of prevalence, but substantial variation by province, and by race within each province, from which we generated provincial total point estimates (EC-74%; FS-75%; GP-68%; ZN-73%; LP-66; MP-73%; NC-63%; NW-81% ) and a 'South Africa minus Western Cape' national prevalence estimate of 71% (95%CI 69-74%). We note that sample collection occurred just before the omicron variant driven wave in South Africa, but otherwise present these results without significant interpretation.

Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial).

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.

Rapid and Successful Implementation of a COVID-19 Convalescent Plasma Programme-The South African Experience.

BACKGROUND: COVID-19 convalescent plasma (CCP) has been considered internationally as a treatment option for COVID-19. CCP refers to plasma collected from donors who have recovered from and made antibodies to SARS-CoV-2. To date, convalescent plasma has not been collected in South Africa. As other investigational therapies and vaccination were not widely accessible, there was an urgent need to implement a CCP manufacture programme to service South Africans. METHODS: The South African National Blood Service and the Western Cape Blood Service implemented a CCP programme that included CCP collection, processing, testing and storage. CCP units were tested for SARS-CoV-2 Spike ELISA and neutralising antibodies and routine blood transfusion parameters. CCP units from previously pregnant females were tested for anti-HLA and anti-HNA antibodies. RESULTS: A total of 987 CCP units were collected from 243 donors, with a median of three donations per donor. Half of the CCP units had neutralising antibody titres of >1:160. One CCP unit was positive on the TPHA serology. All CCP units tested for anti-HLA antibodies were positive. CONCLUSION: Within three months of the first COVID-19 diagnosis in South Africa, a fully operational CCP programme was set up across South Africa. The infrastructure and skills implemented will likely benefit South Africans in this and future pandemics.

Implementation of Option B and a fixed-dose combination antiretroviral regimen for prevention of mother-to-child transmission of HIV in South Africa: A model of uptake and adherence to care.

INTRODUCTION: Initiating and retaining pregnant women on antiretroviral therapy (ART) to prevent mother-to-child HIV transmission (PMTCT) remains a major challenge facing African HIV programs, particularly during the critical final months prior to delivery. In 2013, South Africa implemented its "Option B" PMTCT regimen (three-drug ART throughout pregnancy and breastfeeding, regardless of maternal CD4 count) and introduced once-daily fixed-dose combinations and lifelong ART. Currently, the uptake of Option B and its possible impact on adherence to PMTCT during the critical final months of pregnancy is unclear. MATERIALS AND METHODS: We prospectively collected visit data from a cohort of adult, HIV-infected, pregnant women between July 2013-August 2014 to estimate three models of adherence to PMTCT during the final 16 weeks immediately preceding delivery. Adherence was defined according to possession of antiretroviral drugs, which was inferred from clinic visit records under varying assumptions in each model. We describe uptake of the PMTCT regimen, gestational age at initiation, and model possible scenarios of adherence through delivery after the implementation of Option B. RESULTS: Among 138 women enrolled (median (IQR) age 28 years (24-32), median CD4 count 378 cells/mm3), median (IQR) gestational age at initiation was 22 weeks (16-26). Estimates of adherence during the final 16 weeks of pregnancy prior to delivery ranged from 75% (52-89%) under the best case scenario assumptions to 52% (30-75%) under the worst case scenario assumptions. Estimates of the proportion of women who would achieve 80% adherence to PMTCT were <50% across all models. CONCLUSIONS: Despite the switch to Option B and once-daily dosing, South African women continue to initiate PMTCT late in pregnancy, and estimations of regimen adherence, as modelled using PMTCT visit attendance data, is poor, with <50% of women reaching 80% adherence during final months of pregnancy across all models. Further guideline changes and interventions are needed to achieve vertical transmission goals. TRIAL REGISTRATION: ClinicalTrials.gov NCT01710397 South African National Clinical Trials Register DOH-27-0213-4177.

Initiating antiretroviral therapy for HIV at a patient's first clinic visit: a cost-effectiveness analysis of the rapid initiation of treatment randomized controlled trial.

OBJECTIVE: Determine the cost and cost-effectiveness of single-visit (same-day) antiretroviral treatment (ART) initiation compared to standard of care initiation. DESIGN: Cost-effectiveness analysis of individually randomized (1 : 1) pragmatic trial of single-visit initiation, which increased viral suppression at 10 months by 26% [relative risk (95% confidence interval) 1.26 (1.05-1.50)]. SETTING: Primary health clinic in Johannesburg, South Africa. STUDY PARTICIPANTS: HIV positive, adult, nonpregnant patients not yet on ART or known to be eligible who presented at the clinic 8 May 2013 to 29 August 2014. INTERVENTION: Same-day ART initiation using point-of-care laboratory instruments and accelerated clinic procedures to allow treatment-eligible patients to receive antiretroviral medications at the same visit as testing HIV positive or having an eligible CD4 cell count. Comparison was to standard of care ART initiation, which typically required three to five additional clinic visits. MAIN OUTCOME MEASURE(S): Average cost per patient enrolled and per patient achieving the primary outcome of initiated 90 days or less and suppressed 10 months or less, and production cost per patient achieving primary outcome (all costs per primary outcome patients). RESULTS: The average cost per patient enrolled, per patient achieving the primary outcome, and production cost were $319, $487, and $738 in the standard arm and $451, $505, and $707 in the rapid arm. CONCLUSION: Same-day treatment initiation was more effective than standard initiation, more expensive per patient enrolled, and less expensive to produce a patient achieving the primary outcome. Omitting point-of-care laboratory tests at initiation and focusing on high-volume clinics have the potential to reduce costs substantially and should be evaluated in routine settings.