Assessment of the Impact of Rapid Point-of-Care CD4 Testing in Primary Healthcare Clinic Settings: A Survey Study of Client and Provider Perspectives.

BACKGROUND: The high burden of disease in South Africa presents challenges to public health services. Point-of-care (POC) technologies have the potential to address these gaps and improve healthcare systems. This study ascertained the acceptability and impact of POC CD4 testing on patients' health and clinical management. METHODS: We conducted a qualitative survey study with patients (n = 642) and healthcare providers (n = 13) at the Lancers Road (experienced POC) and Chesterville (non-experienced POC) primary healthcare (PHC) clinics from September 2015 to June 2016. RESULTS: Patients (99%) at Lancers and Chesterville PHCs were positive about POC CD4 testing, identifying benefits: No loss/delay of test results (6.4%), cost/time saving (19.5%), and no anxiety (5.1%), and 58.2% were ready to initiate treatment. Significantly more patients at Chesterville than Lancers Road PHC felt POC would provide rapid clinical decision making (64.7% vs. 48.1%; p < 0.0001) and better clinic accessibility (40.4% vs. 24.7%; p < 0.0001) respectively. Healthcare providers thought same-day CD4 results would impact: Clinical management (46.2%), patient readiness (46.2%), and adherence (23.0%), and would reduce follow-up visits (7.7%), while 38.5% were concerned that further tests and training (15.4%) were required before antiretroviral therapy (ART) initiation. CONCLUSION: The high acceptability of POC CD4 testing and the immediate health, structural, and clinical management benefits necessitates POC implementation studies.

Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1.

Mutational escape by human immunodeficiency virus (HIV) from cytotoxic T-lymphocyte (CTL) recognition is a major challenge for vaccine design. However, recent studies suggest that CTL escape may carry a sufficient cost to viral replicative capacity to facilitate subsequent immune control of a now attenuated virus. In order to examine how limitations can be imposed on viral escape, the epitope TSTLQEQIGW (TW10 [Gag residues 240 to 249]), presented by two HLA alleles associated with effective control of HIV, HLA-B*57 and -B*5801, was investigated. The in vitro experiments described here demonstrate that the dominant TW10 escape mutation, T242N, reduces viral replicative capacity. Structural analysis reveals that T242 plays a critical role in defining the start point and in stabilizing helix 6 within p24 Gag, ensuring that escape occurs at a significant cost. A very similar role is played by Thr-180, which is also an escape residue, but within a second p24 Gag epitope associated with immune control. Analysis of HIV type 1 gag in 206 B*57/5801-positive subjects reveals three principle alternative TW10-associated variants, and each is strongly linked to concomitant additional variants within p24 Gag, suggesting that functional constraints operate against their occurrence alone. The extreme conservation of p24 Gag and the predictable nature of escape variation resulting from these tight functional constraints indicate that p24 Gag may be a critical immunogen in vaccine design and suggest novel vaccination strategies to limit viral escape options from such epitopes.