The clinical effect of point-of-care HIV diagnosis in infants: a systematic review and meta-analysis.

Background: Timely diagnosis and treatment of HIV is crucial in HIV-exposed infants to prevent the high rates of mortality seen during the first 2 years of life if HIV is untreated. However, challenges with sample transportation, testing, and result delivery to caregivers have led to long delays in treatment initiation. We aimed to compare the clinical effect of point-of-care HIV testing versus laboratory-based testing (standard of care) in HIV-exposed infants.

Methods: We did a systematic review and meta-analysis and searched PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Conference Proceedings Citation Index-Science, and WHO Global Index Medicus, from Jan 1, 2014, to Aug 31, 2020. Studies were included if they pertained to the use of point-of-care nucleic acid testing for infant HIV diagnosis, had a laboratory-based nucleic acid test as the comparator or standard of care against the index test (same-day point-of-care testing), evaluated clinical outcomes when point-of-care testing was used, and included HIV-exposed infants aged younger than 2 years. Studies were excluded if they did not use a laboratory-based comparator, a nucleic acid test that had been approved by a stringent regulatory authority, or diagnostic-accuracy or performance evaluations (eg, no clinical outcomes included). Reviews, non-research letters, commentaries, and editorials were also excluded. The risk of bias was evaluated using the ROBINS-I framework. Data were extracted from published reports. Data from all studies were analysed using frequency statistics to describe the overall populations evaluated and their results. Key outcomes were time to result delivery and antiretroviral therapy initiation, and proportion of HIV-positive infants initiated on antiretroviral therapy within 60 days after sample collection.

Findings: 164 studies were identified by the search and seven were included in the analysis, comprising 37 377 infants in total across 15 countries, including 25 170 (67%) who had point-of-care HIV testing and 12 207 (33%) who had standard-of-care testing. The certainty of evidence was high. Same-day point-of-care testing led to a significantly shorter time between sample collection and result delivery to caregivers compared with standard-of-care testing (median 0 days [95% CI 0-0] vs 35 days [35-37]). Time from sample collection to antiretroviral therapy initiation in infants found to be HIV-positive was significantly lower with point-of-care testing compared with standard of care (median 0 days [95% CI 0-1] vs 40 days [36-44]). When each study's result was weighted equally, 90·3% (95% CI 76·7-96·5) of HIV-positive infants diagnosed using point-of-care testing had started antiretroviral therapy within 60 days of sample collection, compared with only 51·6% (27·1-75·7) who had standard-of-care testing (odds ratio 8·74 [95% CI 6·6-11·6]; p<0·0001).

Interpretation: Overall, the certainty of the evidence in this analysis was rated as high for the primary outcomes related to result delivery and treatment initiation, with no serious risk of bias, inconsistency, indirectness, or imprecision. In HIV-exposed infants, same-day point-of-care HIV testing was associated with significantly improved time to result delivery, time to antiretroviral therapy initiation, and proportion of HIV-positive infants starting antiretroviral therapy within 60 days compared with standard of care.

Funding: The Bill & Melinda Gates Foundation.