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In areas of limited resources, point-of-care diagnostic testing is being increasingly used to identify disease, determine prognosis, and monitor treatment. Investments in new diagnostics are starting to improve care. Health systems need to evolve to reap benefits for global health. The investment in health services in low- and middle-income countries has increased substantially in recent years. 1 Such investment has been led by unprecedented efforts to combat major diseases, enabled by the availability of lower-cost and effective drug regimens for treatment and prophylaxis, along with improved vector control. As health services have expanded, so has the demand for diagnostic tests that are essential in identifying patients, determining prognosis, monitoring treatment, and assessing the efficacy of prevention. 2 Classic diagnostic technologies are not well suited to meeting the expanded testing needs. Laboratory tests require complex infrastructure, skilled technicians, and a stable supply of . . .

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. 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. 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). 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. The Bill & Melinda Gates Foundation.

Loss to follow-up of HIV-positive patients before initiation of antiretroviral therapy can exceed 50% in low-income settings and is a challenge to the scale-up of treatment. We implemented point-of-care counting of CD4 cells in Mozambique and assessed the effect on loss to follow-up before immunological staging and treatment initiation. In this observational cohort study, data for enrolment into HIV management and initiation of antiretroviral therapy were extracted retrospectively from patients' records at four primary health clinics providing HIV treatment and point-of-care CD4 services. Loss to follow-up and the duration of each preparatory step before treatment initiation were measured and compared with baseline data from before the introduction of point-of-care CD4 testing. After the introduction of point-of-care CD4 the proportion of patients lost to follow-up before completion of CD4 staging dropped from 57% (278 of 492) to 21% (92 of 437) (adjusted odds ratio [OR] 0·2, 95% CI 0·15–0·27). Total loss to follow-up before initiation of antiretroviral treatment fell from 64% (314 of 492) to 33% (142 of 437) (OR 0·27, 95% CI 0·21–0·36) and the proportion of enrolled patients initiating antiretroviral therapy increased from 12% (57 of 492) to 22% (94 of 437) (OR 2·05, 95% CI 1·42–2·96). The median time from enrolment to antiretroviral therapy initiation reduced from 48 days to 20 days (p<0·0001), primarily because of a reduction in the median time taken to complete CD4 staging, which decreased from 32 days to 3 days (p<0·0001). Loss to follow-up between staging and antiretroviral therapy initiation did not change significantly (OR 0·84, 95% CI 0·49–1·45). Point-of-care CD4 testing enabled clinics to stage patients rapidly on-site after enrolment, which reduced opportunities for pretreatment loss to follow-up. As a result, more patients were identified as eligible for and initiated antiretroviral treatment. Point-of-care testing might therefore be an effective intervention to reduce pretreatment loss to follow-up. Absolute Return for Kids and UNITAID.

Failure to timely diagnose HIV in infants is a major barrier for scaling-up paediatric antiretroviral treatment (ART). WHO recommends birth testing for earlier diagnosis and to improve test coverage, but current diagnosis takes 2-3 weeks to complete, thereby limiting the ability of care givers to provide follow-on care, especially in low-resource settings. We evaluated the benefit of implementing rapid diagnosis of HIV at birth in primary health care maternity wards in Mozambique. Infants born to HIV-infected mothers delivering consecutively at eight primary health care clinics were tested within 24 hours of delivery using on-site POC (Alere q HIV1/2 Detect) and standard laboratory (Roche COBAS AmpliPrep/TaqMan HIV-1 qualitative assay v2.0) testing. Infants were also tested at 4-6 weeks of age with both assays. Of 2,350 HIV-exposed infants enrolled in this implementation research study, 33 tested HIV-positive at birth on both assays. Sensitivity and specificity of POC testing compared with laboratory testing at birth were 100% (95% CI 89·4-100·0) and 100% (95% CI 99·8-100·0), respectively. At 4-6 weeks of age, 61 infants were identified as HIV-positive; of these 29 (47·5%) had a positive test at birth. Testing at both birth and 4-6 weeks identified 71 HIV-positive infants compared with 61 infants by testing at 4-6 weeks alone, a 16% increase. Two infants tested positive at birth but tested HIV-negative during follow-up. Adding POC birth testing to the 4-6 week screen may increase access to HIV diagnosis and expedite ART initiation in primary health care settings within low resource settings. Guidance on appropriate confirmatory HIV testing algorithms for birth testing is needed.

The long delay in returning test results during early infant diagnosis of HIV (EID) often causes loss-to-follow-up prior to antiretroviral treatment (ART) initiation in resource-limited settings. A point-of-care (POC) test may help overcome these challenges. We evaluated the performance of the LYNX p24 Antigen POC test in Mozambique. 879 HIV-exposed infants under 18 months of age were enrolled consecutively at three primary healthcare clinics (PHC). Lancet heel-drawn blood was tested on-site by nurses using a prototype POC test for HIV Gag p24 antigen detection. Results of POC testing were compared to laboratory-based nucleic acid testing on dried blood spots. A comparison of the effect of sensitivity and timely test results return on successful diagnosis by POC and laboratory-based platforms was also calculated. The sensitivity and specificity of the LYNX p24 Ag test were 71.9%; (95% confidence interval [CI]: 58.5-83.0%) and 99.6% (95% CI: 98.9-99.9%), respectively. The predictive value of positive and negative tests were 93.2% (95% CI: 81.3-98.6%) and 97.9% (95% CI: 96.8-98.8%), respectively. Overall agreement was high (Cohen Kappa = 0.80; 95% CI: 0.71-0.89). Despite its lower sensitivity, the POC test had the potential to provide test results to up to 81% more patients compared to the laboratory-based test. This prototype POC p24 assay was feasible for use in PHCs but demonstrated low sensitivity for HIV detection. POC EID technologies that perform below standard recommendations may still be valuable diagnostic tools in settings with inefficient EID networks.

Vaccine efficacy testing requires engagement of willing volunteers with high disease incidence. We evaluated factors associated with willingness to participate in potential future HIV vaccine trials in Maputo, Mozambique. Adults aged 18-35 years without HIV and who reported at least two sexual partners in the 3 months prior to screening were enrolled into a 24-month observational study. They were asked at screening and exit if they would be willing to participate in a theoretical HIV vaccine study. Bivariate and multivariate logistic regression analyses were done between willingness to participate, demographic, sexual behavior, and motivational factors for screening visit data. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors potentially associated with willingness to participate for data from both visits. A total of 577 participants without HIV were eligible, including 275 (48%) women. The mean age was 22.2 (SD ± 3.9) years. At screening 529 (92%) expressed willingness to participate and the proportion remained stable at 378 (88%) of the 430 participants retained through the exit visit (p = 0.209). Helping the country (n = 556) and fear of needles (n = 26) were the top motive and barrier for willingness to participate, respectively. Results from the GEE binary logistic regression (screening visit and exit visit) showed that wanting to learn how to avoid risk behaviors (aOR 3.33, 95% CI: 1.61-6.86) and feeling protected against HIV infection (aOR 2.24, 95% CI: 1.07-4.7) were associated with willingness to participate in HIV vaccine studies. The majority of our study population in Mozambique expressed willingness to participate in a theoretical HIV vaccine trial. Participation in a HIV vaccine trial was seen as a way to contribute to the fight against HIV but was associated with some unrealistic expectations such as protection against HIV. This reinforces the need for continuous mobilization and awareness of potential participants to HIV vaccine trial.

In this comparative biomarker study, we analysed 1768 serial sputum samples from 178 patients at 4 sites in Southeast Africa. We show that tuberculosis Molecular Bacterial Load Assay (TB-MBLA) reduces time-to-TB-bacillary-load-result from days/weeks by culture to hours and detects early patient treatment response. By day 14 of treatment, 5% of patients had cleared bacillary load to zero, rising to 58% by 12th week of treatment. Fall in bacillary load correlated with mycobacterial growth indicator tube culture time-to-positivity (Spearmans r=−0.51, 95% CI (−0.56 to −0.46), p<0.0001). Patients with high pretreatment bacillary burdens (above the cohort bacillary load average of 5.5log10eCFU/ml) were less likely to convert-to-negative by 8th week of treatment than those with a low burden (below cohort bacillary load average), p=0.0005, HR 3.1, 95% CI (1.6 to 5.6) irrespective of treatment regimen. TB-MBLA distinguished the bactericidal effect of regimens revealing the moxifloxacin—20 mg rifampicin regimen produced a shorter time to bacillary clearance compared with standard-of-care regimen, p=0.008, HR 2.9, 95% CI (1.3 to 6.7). Our data show that the TB-MBLA could inform clinical decision making in real-time and expedite drug TB clinical trials.

Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique. We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%-61.0%), increasing to 65.0% (95% CI, 64.9%-65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6-9.6 y) and US$2,440 (95% CI, US$2,440-US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3-10.3 y) and US$2,800 (95% CI, US$2,790-US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480-US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4. POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors' Summary.

Scaling up access to HIV viral load testing for individuals undergoing antiretroviral therapy in low-resource settings is a global health priority, as emphasised by research showing the benefits of suppressed viral load for the individual and the whole population. Historically, large-scale diagnostic test implementation has been slow and incomplete because of service delivery and other challenges. Building on lessons from the past, in this Personal View we propose a new framework to accelerate viral load scale-up and ensure equitable access to this essential test. The framework includes the following steps: (1) ensuring adequate financial investment in scaling up this test; (2) achieving pricing agreements and consolidating procurement to lower prices of the test; (3) strengthening functional tiered laboratory networks and systems to expand access to reliable, high-quality testing across countries; (4) strengthening national leadership, with prioritisation of laboratory services; and (5) demand creation and uptake of test results by clinicians, nurses, and patients, which will be vital in ensuring viral load tests are appropriately used to improve the quality of care. The use of dried blood spots to stabilise and ship samples from clinics to laboratories, and the use of point-of-care diagnostic tests, will also be important for ensuring access, especially in settings with reduced laboratory capacity. For countries that have just started to scale up viral load testing, lessons can be learnt from countries such as Botswana, Brazil, South Africa, and Thailand, which have already established viral load programmes. This framework might be useful for guiding the implementation of viral load with the aim of achieving the new global HIV 90-90-90 goals by 2020.

[...]same-day results were returned to caregivers 97% of the time, while 51% of infants living with HIV initiated ART on the same day as sample collection versus 0% for both metrics when tested using laboratory-based testing. [...]maximizing the impact of point-of-care testing will require strengthening of treatment and care services for children, including expanding efforts to identify mothers with HIV infection and infants at risk, same-day linkage of infants to treatment and care, reliable procurement of appropriate paediatric antiretroviral formulations and high-quality health services addressing the needs of families with HIV infection. Indicating that modest procurement and focused placement of point-of-care technologies would affect a considerable proportion of at-risk infants [ 13, 15]. [...]point-of-care technologies may not need to be procured for every healthcare facility to reach most HIV-exposed infants.