CROI 2023: Point-of-care testing for mothers and infants: results from the LIFE study
Polly Clayden, HIV i-Base
Point-of-care maternal viral load testing at delivery significantly increased the proportion of infants judged to be at high-risk for HIV. In turn these high-risk infants were more likely to be started on enhanced prophylaxis.
And, among infants with HIV, point-of-care testing at birth plus early ART initiation led to a reduction in early mortality.
These findings from the LIFE study were shown in two oral presentations at CROI 2023. [1, 2]
LIFE was conducted at 28 rural, primary healthcare facilities in Tanzania and Mozambique. This cluster-randomised study looked at the benefits novel point-of-care diagnostic systems that provide fast results.
It evaluated point-of care maternal viral load testing at delivery to identify infants at high risk of vertical transmission – so they could be given enhanced prophylaxis.
It also evaluated infant HIV testing at birth followed by immediate neonatal ART initiation to see if this led to a reduction in morbidity, HIV progression and death compared with the current standard of testing infants six weeks after delivery.
Point-of-care maternal viral load testing
This part of the study aimed to evaluate point-of-care maternal viral load testing at delivery and its role in assessing vertical transmission risk, and whether this was linked to providing enhanced neonatal prophylaxis.
WHO defines high-risk infants as those whose mothers were first diagnosed at delivery or post-partum, acquired HIV during pregnancy or breastfeeding, started ART late in pregnancy (received less than 4 weeks before delivery) or did not achieve viral suppression (<1000 copies mL) by the time of delivery. Enhanced neonatal prophylaxis (AZT plus nevirapine) is recommended for the first six weeks of life plus an extra six weeks during breastfeeding.
Arm A (intervention) included point-of-care maternal viral load testing to infant high-risk assessment, as well as clinical criteria and antenatal care information as available in the control arm B (control).
In Tanzania both arms started enhanced neonatal prophylaxis based on maternal risk factors, including viral load for arm A, and low-risk infants received nevirapine alone. In Mozambique, enhanced neonatal prophylaxis is universal.
The investigators estimated the effect of point-of-care maternal viral load testing on the proportion of infants: identified as high-risk (Tanzania and Mozambique) and high-risk infants receiving enhanced neonatal prophylaxis (Tanzania).
The evaluation enrolled 6512 mothers living with HIV: 28% were diagnosed in the third trimester, 99% were on ART (76.5% dolutegravir-based) for a median of 6.05 months but 21.9% were not virally suppressed (<1000 copies/mL) at delivery.
Of 6568 infants, 19% vs 4% in arm A and B respectively, were classified as high-risk (p<0.001). In arm A, 82.5% of infants were classified using the result from the point-of-care maternal viral load test at delivery. And 96% with multiple high-risk criteria had high viral load at delivery. In arm B, as well as the 4% of infants, identified based on other criteria, a further 22%, had mothers with unsuppressed viral load at delivery.
In Tanzania, high-risk infants in arm A were significantly more likely to receive enhanced neonatal prophylaxis: 59.8% vs 31.4% in arms A and B, respectively, OR 3.75 (95% CI: 1.34 to 10.49). But, 40.2% in arm A and 68.6% in arm B did not receive enhanced neonatal prophylaxis, despite available information for high-risk classification at delivery.
Early infant diagnosis and ART initiation
Point-of-care testing and rapid ART initiation was shown to be feasible in the second presentation from the LIFE study. This resulted in a relative reduction of 67% in mortality during the first six months of life – although this did not reach statistical significance.
Early mortality among infants with HIV is high and peaks at 2–3 months of life. Late diagnosis delays access to ART, often past this high-risk period.
This study assessed the impact of a point-of-care HIV early infant diagnosis and ART initiation at birth on viral suppression and early mortality.
Arm A sites (intervention) provided point-of-care early infant diagnosis and immediate ART initiation for those with HIV at birth, while control arm B sites (control) offered point-of-care early infant diagnosis and linkage to ART from 4–6 weeks of age. ART initiation was nurse-led.
Infant ART at birth was nevirapine plus AZT and 3TC. By 4–6 weeks infants were switched or started on lopinavir/r plus abacavir and 3TC granules.
The study was designed with a 12 week estimated vertical transmission rate of 4%. But, the actual transmission rate was considerably lower. Among 6605 infants enrolled, 124 were diagnosed with HIV by 12 weeks of age: overall transmission rate 1.88% (95% CI 1.56 to 2.23). About 50% of transmissions occurred at delivery.
Transmission was lower in Tanzania than Mozambique: 0.62% vs 2.69% at 12 weeks (p<0.001).
A small proportion (8.9%) of mothers were not on ART at delivery or had unknown status. The majority (90.3%) had viral load >1000 copies/mL at delivery, so were on failing regimens. Most mothers were receiving dolutegravir-based ART. In an interim analysis around 50% had nevirapine resistance.
In Arm A, median infant point-of-care turnaround time was 20.3 hours and time to ART initiation was 23 hours.
Viral suppression was 38% vs 6% at week 4–6 in arm A and B respectively (p=0.001); 59% among infants starting ART at birth. This difference was 66% vs 30% at 18 months (p=0.005).
By month 6 infant mortality was lower in arm A vs arm B: 5.8% vs 14.5%, aHR 0.328 (95% CI 0.099 to 1.093), p=0.07. But numbers were small (4 vs 8) and this difference did not reach statistical significance. The difference was not maintained at months 12 and 18. When mortality was combined with severe clinical events, retention or a combination of outcomes, there was no difference between arms.
In terms of implementation, these results demonstrate that both maternal viral load and infant diagnostic testing are feasible in very rural primary care settings. Nurses performed the tests and turnaround time was impressive.
In the first evaluation, the investigators noted that although point-of-care maternal viral load testing identified more infants at high risk of vertical transmission, use of enhanced neonatal prophylaxis was still suboptimal. Universal enhanced prophylaxis in regions with a large proportion of high-risk infants seems preferable but in regions with a smaller proportion of high-risk infants this would mean unnecessary exposure of many of them to AZT.
In the second evaluation the low vertical transmission rates were also impressive – particularly in Tanzania –and this was despite many mothers being on failing regimens. The low transmission rate meant that the study was underpowered. The target sample size was 224 infants with HIV and this assessment included 124. So the effect of early infant diagnosis and immediate ART might be underestimated.
Viral suppression rates in the infants were also lower than expected during follow up in the intervention arm (around 30% at 3 to 6 months). The investigators suggested that the palatability of the granules might help to explain this, especially as the infants grew and needed more. Lack of disclosure in the mothers and giving the granules secretly to their infants was a challenge. By 18 months there was a difference in suppression rates, favouring the intervention arm, but by this time some of the children had switched to dolutegravir-based ART and this was not integrated into the analysis.
It would be interesting to see the results using dolutegravir-based ART early on.
- Lwilla AF et al. Maternal point-of-care viral load at delivery impacts infant ARV prophylaxis regimen. 30th Conference on Retroviruses and Opportunistic Infections, 19–22 February 2023, Seattle. Oral abstract 129.
- Kroidl A et al. Birth point-of-care test & treat reduces early mortality among HIV-infected infants. . 30th Conference on Retroviruses and Opportunistic Infections, 19–22 February 2023, Seattle. Oral abstract 132.
This report was first published on 7 March 2023.