Uptake of early infant diagnosis and factors associated with its timely completion among HIV exposed infants at Lira Regional Referral Hospital: a retrospective cohort study

This retrospective cohort study at Lira Regional Referral Hospital found that while early infant diagnosis uptake among HIV-exposed infants was sub-optimal compared to national targets, timely administration of cotrimoxazole was significantly associated with the timely completion of the diagnosis process.

The Gist

Imagine a high-stakes relay race where the goal is to keep a baby healthy. The runners are the mothers, the doctors, and the babies themselves. The baton they are passing is a series of HIV tests.

If the baby is born to a mother living with HIV, there is a risk the baby might have the virus too. To stop this, doctors have a strict schedule: test the baby at 6 weeks, again at 9 months, again 6 weeks after breastfeeding stops, and one last time at 18 months. If the baby tests positive early, they get medicine immediately and can live a long, healthy life. If they miss a test, the baby might get sick without anyone knowing.

This paper is a report card on how well this relay race is being run at Lira Regional Referral Hospital in Uganda.

The Race Track: What They Did

The researchers looked back at the records of 252 babies born in 2021. They acted like detectives, checking the "race logs" (medical files) to see:

1. Did the baby show up for the test?
2. Did they show up on time?

The Results: Who Crossed the Finish Line?

The results were a mix of good news and some serious stumbling blocks:

• The Start (6 Weeks): This was a strong start. About 80% of the babies showed up on time.
  • Why? It's like a "double-header" event. At 6 weeks, babies usually get their first big round of vaccines (for polio, tetanus, etc.). Moms are already there, so it's easy to add the HIV test to the list.
• The Middle (9 Months): Still doing well, with 84% showing up on time.
  • Why? Again, this lines up with the measles vaccine. The "vaccine bus" is making a stop, and the HIV test gets a free ride.
• The Big Drop (6 Weeks after Breastfeeding): This is where the race fell apart. Only 3.7% of babies took this test on time.
  • The Problem: This test doesn't line up with any vaccines. It's like asking a runner to show up to the track on a random Tuesday just to run a lap, with no other reason to be there. Also, many moms were confused about the timing (told to come back 2 months later instead of 6 weeks).
• The Finish Line (18 Months): The numbers bounced back to 79%.
  • Why? This coincides with the second measles shot and deworming medicine. The "vaccine bus" is back in town.

The Bottom Line: While most babies get tested at the start and the end, a huge gap exists in the middle. Because of this, many babies leave the hospital without a final "all-clear" stamp, leaving their health status a mystery.

The Secret Weapon: Cotrimoxazole

The study found one specific factor that acted like a super-connector for the race: Cotrimoxazole.

This is a daily antibiotic pill given to HIV-exposed babies to prevent other infections (like pneumonia). The study found that babies who got this pill were much more likely to complete their HIV tests on time.

• The Analogy: Think of Cotrimoxazole as a "daily check-in" with the clinic. Because the mom has to come in every day or week to pick up the medicine, she is already in the system. It keeps her connected to the healthcare team, so when it's time for the big HIV test, she doesn't get lost.

What Didn't Matter (Surprisingly)

The researchers expected that things like how far the mom lived from the hospital or how old the mom was would be the main reasons for missing tests.

• The Reality: In this specific study, distance and age didn't seem to stop people. The main issue wasn't getting to the hospital; it was remembering to come back for the specific test that didn't have a vaccine attached to it.

The Takeaway

The hospital is doing a good job when the HIV test is "bundled" with vaccines. But when the test stands alone (like the one after breastfeeding stops), the system breaks down.

To fix the race, the authors suggest:

1. Better Signposting: Make sure moms know exactly when to come back for the "orphan" test that doesn't have a vaccine.
2. Keep the Connection: Continue giving Cotrimoxazole, as it seems to keep families engaged with the clinic.
3. Community Helpers: Use local community workers to remind moms, acting like a personal coach for the race.

In short, the hospital has the map, but they need to build better bridges to get the runners across the gaps in the middle of the race.

Technical Summary

1. Problem Statement

Despite the availability of Prevention of Mother-to-Child Transmission (PMTCT) guidelines in Uganda, the uptake of Early Infant Diagnosis (EID) for HIV-exposed infants (HEIs) remains sub-optimal. While global and national targets aim for 90% coverage, previous studies in Uganda indicate significant gaps: only 64% of HEIs receive their first DNA-PCR test, fewer than 55% are tested within two months, and only 28% complete the final rapid test at 18 months.

Specific challenges include high loss to follow-up (51% at Lira Regional Referral Hospital), barriers such as stigma, distance to facilities, and inadequate staffing. Crucially, there is a lack of comprehensive data on the timely completion of the entire EID cascade (1st, 2nd, and 3rd DNA-PCR tests, plus the final rapid test) and the specific factors influencing adherence to these timelines at regional referral hospitals.

2. Methodology

• Study Design: Retrospective cohort study.
• Setting: Lira Regional Referral Hospital (LRRH), Northern Uganda.
• Population: 252 HIV-exposed infants born between January 1, 2021, and December 31, 2021.
• Sampling: Consecutive sampling was used to select eligible mother-baby pairs from EID registers and files. Exclusion criteria included missing infant cards or transfers to other facilities.
• Data Collection: Data was abstracted from mother-baby pair files and EID registers between July 3 and July 17, 2023. Variables included socio-demographics, clinical characteristics (maternal age, marital status, viral load, ART prophylaxis, cotrimoxazole use), and EID testing timelines.
• Outcome Measures:
  • Primary Outcome: Uptake of EID classified as "timely" (tested within the WHO/PMTCT guideline timeframe) or "untimely" (tested late or not tested).
  • Time Points:
    1. 4–6 weeks (1st DNA-PCR)
    2. 9 months (2nd DNA-PCR)
    3. 6 weeks after cessation of breastfeeding (3rd DNA-PCR)
    4. 18 months (Final Rapid Test)
• Statistical Analysis:
  • Descriptive statistics for baseline characteristics.
  • Generalized Estimating Equations (GEE) with a Poisson family, log link, and unstructured correlation structure were used to account for repeated measures over time.
  • Bivariate analysis identified variables with interaction p-values <0.2 for multivariate modeling.
  • Multivariate analysis assessed adjusted relative risks (aRR) for factors associated with timely completion.

3. Key Results

• EID Uptake Rates:

  • 4–6 Weeks: 80.1% (95% CI: 74.5–84.7)
  • 9 Months: 84.2% (95% CI: 79.0–88.3)
  • 6 Weeks Post-Breastfeeding: 3.7% (95% CI: 2.0–7.0) — Critically low.
  • 18 Months: 78.8% (95% CI: 73.2–83.6)
  • Observation: All rates fell below the Ministry of Health's 90% target. The drop at the 6-week post-breastfeeding mark was the most significant failure point.

• Factors Associated with Timely Completion (Multivariate Analysis):

  • Cotrimoxazole Prophylaxis: Infants who did not receive cotrimoxazole were significantly associated with timely completion compared to those who did (aRR = 2.97; 95% CI: 1.45–6.10). The study notes this counter-intuitive finding may be due to confounding factors (e.g., infants receiving cotrimoxazole might have had more complex health issues or different care pathways).
  • Time Point Interaction: The timing of the test significantly influenced outcomes. The 3rd PCR (Time 3) showed the strongest association with delays, likely because it does not coincide with routine immunization schedules.
  • Non-Significant Factors: Contrary to some literature, factors such as distance from the facility, maternal age, feeding status, ART prophylaxis, and time of HIV diagnosis were not statistically significant predictors of timely completion in this specific cohort.

4. Key Contributions

• Granular Temporal Analysis: Unlike studies focusing solely on the first PCR, this research provides a comprehensive breakdown of uptake across all four critical EID time points, highlighting the specific collapse in adherence at the "6 weeks post-breastfeeding" stage.
• Identification of Systemic Gaps: The study identifies that the misalignment of the 3rd PCR test with immunization schedules is a major driver of low uptake, suggesting that integrating EID with routine child health visits is critical.
• Contextual Evidence: It provides specific data from a regional referral hospital in Northern Uganda, a setting often underrepresented in national aggregate data, revealing high retention rates at immunization-linked visits but poor retention for standalone testing.

5. Significance and Implications

• Policy Recommendations: The findings suggest that to meet the 90% target, the Ministry of Health must decouple EID testing from the assumption that mothers will return solely for HIV testing. Interventions should focus on:
  • Scheduling: Aligning the 3rd PCR (post-breastfeeding) with other scheduled child health activities or providing specific reminders.
  • Counseling: Correcting misconceptions about appointment timing (e.g., mothers instructed to return 2 months post-weaning instead of 6 weeks).
  • Supervision: Strengthening mentorship for healthcare workers to ensure adherence to PMTCT guidelines.
• Future Research: The study highlights the need for mixed-methods research to understand why distance and feeding status were not significant in this cohort, and to investigate unmeasured confounders like household income and parental education, which were not captured due to record limitations.
• Public Health Impact: Improving the completion of the EID cascade is vital for reducing infant mortality. Infants who miss the final rapid test at 18 months remain in a state of "unknown status," preventing timely ART initiation and increasing the risk of AIDS-related mortality.

Limitations: The study relied on retrospective record abstraction, leading to missing data on socio-economic variables (income, education). The use of consecutive sampling limits generalizability, and the counter-intuitive finding regarding cotrimoxazole requires further investigation to rule out confounding.