Globally, there are approximately 1.57 million (1,200,000-1,900,000) adolescents (10-19 y) living with HIV, most with perinatally acquired HIV (PHIV) and living in low- and middle-income countries (LMICs), with approximately 85% living in sub-Saharan Africa (SSA) [1,2]. Greater access to more effective antiretroviral therapy (ART) has greatly improved their health outcomes [3,4], allowing adolescents with HIV to live well into adulthood [5,6]. Despite this public health success, adolescents with PHIV remain at high risk for a variety of complications, including neurocognitive problems [7,8].

As many as 46% of adolescents with PHIV experience neurocognitive problems [9], despite viral suppression [10,11]. Although both the persistence of HIV and its downstream effects in the central nervous system are thought to play a key role in these complications [12], low socioeconomic status, limited educational opportunities, early life adversity, and other comorbidities are also likely contributing factors [11,13,14]. PHIV typically affects the neurocognitive domains of processing speed and executive functioning [9]. Neurocognitive problems have been associated with poor academic performance, suboptimal ART adherence, increased mental health problems, poor decision-making, and engagement in HIV transmission and other risk behaviors (eg, unprotected sex) [11,15-29].

Early detection of neurocognitive problems can allow for ART regimen adjustments, tailored support approaches, better coping, and earlier intervention [30]. Without timely intervention, these problems may accumulate, limiting adolescents’ future independence, employment potential, and quality of life [31]. However, detection of neurocognitive problems is challenging in LMICs for several reasons [32,33]. First, many LMICs, including those in SSA, have a limited number of psychologists and/or neuropsychologists trained to administer, score, and interpret traditional neuropsychological test batteries to measure and diagnose neurocognitive problems [34]. For example, in Uganda, where the current study took place, there are only 0.04 psychologists per 100,000 people, compared with 31.3 per 100,000 in the United States [35,36]. The precise number of neuropsychologists and/or psychologists with specialized neuropsychology training in Uganda is not known.

Second, access to culturally and linguistically appropriate neurocognitive tests is limited. Most tests to date were designed for use by English speakers in high-income countries and, as such, may only be available in English, which may be inappropriate for other cultures and contexts [37-39]. While English is often considered an official language of government and taught in schools in many LMICs, including Uganda, many communities rely on their indigenous languages and local dialects for everyday activities and may not be fully fluent in the officially recognized languages [37,40]. Administering English-language tests in communities that prefer or rely on other languages not only produces invalid test results but also violates ethical practices for psychologists and standardized testing practices [41,42]. Finally, traditional test batteries often require multiple hours to complete—time and resources that overburdened and resource-constrained health care systems in LMICs do not have.

Computerized neurocognitive tests, particularly those that are tablet-based, show promise for use in LMICs and may help make testing more accessible to LMIC populations [43-45]. Compared with traditional tests, computerized tests are highly automated, and many have been designed for administration by a wide variety of personnel who do not have specialized training. Tablet-based tests are also highly portable, and tablets are considerably more affordable than desktop or laptop computers [46,47].

NeuroScreen is a tablet-based battery of neurocognitive tests designed for resource-limited settings [48-50]. It has been validated for use in adult populations with HIV in South Africa [48] and among patients with first-episode psychosis in Uganda [51], as well as with adolescents and young adults with PHIV in Thailand [49] and the United States [39]. This cross-sectional validation study evaluated the construct validity (ie, convergent validity, known-groups validity, and criterion validity), as well as acceptability, of a Luganda-language–adapted NeuroScreen for use among adolescents in Uganda living with PHIV. We hypothesized that performance on the NeuroScreen battery would be positively correlated with performance on a traditional battery of neurocognitive tests assessing similar domains, that adolescents with PHIV would perform worse than controls on both batteries, and that the 2 batteries would show agreement in the proportion of participants scoring ≤1 SD and ≤2 SD below the global mean.

In this study, we adapted NeuroScreen for use with English- and Luganda-speaking Ugandan adolescents and examined its construct and criterion validity compared with a widely used traditional test battery. Overall, the findings support the use of NeuroScreen as a brief, tablet-based approach for assessing neurocognitive functioning in this population. Global performance on NeuroScreen was strongly correlated with global performance on the traditional battery, and adolescents with PHIV performed more poorly than HIV-negative controls on both batteries. Tests assessing similar domains had small to moderate correlations.

Convergent validity was most clearly supported by the strong, statistically significant correlation between the global z-scores derived from NeuroScreen and the traditional battery (r=0.75). Correlation coefficients between conceptually similar processing speed tests were among the highest (r=0.37-0.48), with conceptually similar tests of attention and working memory having similar correlations (r=0.30-0.47), and a conceptually similar executive functioning test showing a moderate correlation (r=0.34). These findings are encouraging because an exact one-to-one correspondence between computerized and traditional tests is not necessarily expected, even when they are intended to assess similar domains [65,66]. Differences in modality, response demands, timing parameters, and stimulus format may account for the modest, rather than large, test-level correlations [65-67].

Furthermore, the modest test-level correlations are likely a function of the NeuroScreen tests being considerably shorter than the traditional battery tests (eg, coding has a time limit of 120 s vs 45 s for the NeuroScreen visual discrimination 2 test, and thus the latter yields fewer scorable responses). Hence, each NeuroScreen test comprises fewer items than its traditional counterpart and therefore, by classical test theory, carries less measurement information and lower reliability, meaning briefer tests will correlate more weakly with longer traditional tests even when both assess closely related constructs [68-70]. This is the pattern we observed, and for this reason, the global scores, which aggregate scores across many subtests and thus represent greater length and reliability, are a more appropriate index of convergent validity. This also carries an important implication for NeuroScreen. The approximately 25-minute NeuroScreen battery shares approximately 56% of the variance with the traditional battery (r=0.75 or r²=0.56), which requires 120 to 180 minutes to administer (and more time to score and interpret). NeuroScreen captures much of the same signal as the traditional battery at a small fraction of the assessment burden—an efficiency especially valuable in low-resource settings.

NeuroScreen was able to distinguish performance between adolescents with PHIV and controls. Adolescents with PHIV had significantly worse global performance on NeuroScreen compared with controls. This finding was the same for the traditional battery. Adolescents with PHIV performed worse than controls on all but 2 individual tests and significantly worse on 4 tests in the NeuroScreen battery, compared with 6 tests in the traditional battery, and this pattern mostly remained after age adjustment. When adjusting for the FDR on unadjusted comparisons, only 3 of the traditional battery tests remained significant. When adjusting for the FDR on age-adjusted comparisons, only 2 of the traditional battery tests remained significant. Notably, the magnitude of the group differences was similar across batteries, suggesting that NeuroScreen was sensitive to the neurocognitive difficulties associated with PHIV in this sample. These findings are consistent with prior work from Uganda and other settings showing that youth with PHIV remain at risk for neurocognitive difficulties despite access to ART [61,62,71]. They also extend prior NeuroScreen validation work in PHIV-affected youth and Ugandan clinical populations by demonstrating similar performance with a Luganda-adapted version among Ugandan adolescents [39,49,51].

At the domain level, the most consistent differences between participants with PHIV and controls were observed in processing speed and executive functioning. This pattern is broadly in line with the literature on HIV-associated neurocognitive difficulties in youth, for whom slowed processing speed and executive inefficiencies are among the most commonly reported deficits [9,71,72]. In contrast, differences in learning and memory were significant in unadjusted analyses but were attenuated after age adjustment. Working memory differences were in the expected direction but did not reach statistical significance. These findings suggest that NeuroScreen may be especially useful for detecting the domains most consistently affected in PHIV, while also highlighting that not all cognitive domains are equally discriminating in a relatively small sample of virally suppressed youth. Importantly, the absolute differences in mean global z-scores between groups were modest, which may reflect the relatively good clinical status of this cohort, all of whom were virally suppressed. Even so, both batteries detected meaningful between-group differences, indicating that subtle but measurable neurocognitive vulnerability persists in this population.

The classification results provide additional support for criterion validity. Both batteries identified more participants with PHIV than controls at ≤1 SD and ≤2 SD below the sample mean global z-scores. Between-group differences in classification rates were only statistically significant in the traditional battery at ≤1 SD below the mean threshold. There was a moderate level of agreement between the batteries in their classifications. Given the modest sample size and the small number of participants falling below the classification thresholds, these analyses should be interpreted cautiously. Still, the convergence between the 2 batteries suggests that NeuroScreen may have utility not only for continuous assessment of neurocognitive performance but also for identifying youth who may warrant more comprehensive follow-up evaluation.

A major strength of NeuroScreen in this context is its feasibility for scale-up. Neurocognitive assessment in many low-resource settings is constrained by shortages of trained specialists, limited availability of culturally and linguistically appropriate tools, and the time burden of traditional batteries. NeuroScreen addresses several of these barriers by standardizing administration, automating scoring, and reducing administration time. In its current form, NeuroScreen only requires approximately 25 minutes to complete and provides information in line with traditional neuropsychological test batteries, which require considerably more time to complete and score (some batteries can require 2‐6 h just for administration). This is particularly relevant in Uganda and similar LMIC settings, where specialist neuropsychology resources are scarce. The successful Luganda adaptation also underscores the importance of culturally and linguistically grounded test development. Rather than simply translating instructions literally, the adaptation process aimed to preserve meaning and comprehensibility for local users, which is essential for valid assessment [55].

Acceptability findings further support the promise of NeuroScreen for use in Uganda. Although many participants had never previously used a tablet, most reported that the app was easy to use. This is notable because familiarity with digital devices is often raised as a concern when introducing tablet-based assessments in low-resource settings [67,73,74]. In this sample, limited prior tablet experience did not appear to prevent successful completion of, or favorable impressions of, the assessment. These findings suggest that, with appropriate orientation and localized instructions, NeuroScreen can be acceptable even among youth with limited exposure to this specific technology platform.

Several limitations should be acknowledged. First, this was a relatively small cross-sectional study, which limited statistical power, particularly for impairment classification analyses and finer-grained domain comparisons. Second, the traditional battery used as the comparator is not a true gold standard for neurocognitive assessment in this context. As in many LMIC settings, available traditional neuropsychological tests themselves have limitations related to cultural fit, language, and normative data. Accordingly, this study should be understood as evaluating NeuroScreen against a commonly used battery of tests rather than against a definitive reference standard. Relatedly, because no published normative data exist for adolescent populations in Uganda for either battery’s tests, sample-based z-scores were used, which can inflate agreement. Third, because all participants with PHIV were virally suppressed and were recruited from an existing urban research cohort, findings may not generalize to youth with less stable HIV disease, those not engaged in care, or more socioeconomically diverse populations. Fourth, several of the traditional measures were administered to participants who exceeded the tests’ published upper age limits (KABC-II, 18 y; CCTT, 17 y; WISC-IV, 16 y). Because we anticipated that most participants would be near 16 years of age and wanted every participant to complete an identical battery, we selected the younger-age forms for the full sample. Administering tests beyond their normed age ranges can affect the validity of age-referenced interpretation and may compress scores near the top of the range, potentially attenuating between-group differences. To assess this, we inspected scatterplots of raw scores against age for each affected test and found no evidence of ceiling effects among older participants. Because our analyses relied on sample-based z-scores rather than the tests’ published norms, the influence of exceeding the normative age ranges on our findings is likely limited, though it cannot be fully excluded. Fifth, to optimize study workflow, we did not counterbalance the order of battery administration. As such, order, practice, or fatigue effects on the second (traditional) battery cannot be ruled out. Sixth, we note that the data were collected 4 to 5 years ago. Nonetheless, we do not believe this would have much bearing on interpretation of the findings because the study evaluates psychometric properties of the adapted tests, which are not time-sensitive. In addition, the versions of the NeuroScreen and the traditional battery tests have not changed. Furthermore, the clinical profile of the virally suppressed Ugandan adolescents with PHIV has remained largely unchanged. Moreover, the shortage of neuropsychology specialists and valid neuropsychological tests for Luganda-speaking populations also remains. Finally, because this study focused on validity and acceptability, additional work is still needed to establish clinical cut-points, longitudinal sensitivity, and predictive utility for functional outcomes such as school performance, medication adherence, and daily functioning.

Despite these limitations, the present findings have important implications. NeuroScreen offers a brief, scalable, and locally adapted approach to neurocognitive assessment that showed a similar pattern of group differences to a traditional neuropsychological test battery. In settings where the use of traditional neuropsychological test batteries is not feasible or practical, a tool such as NeuroScreen could expand access to screening and help identify youth who may benefit from monitoring, referral, or intervention. Future studies should examine its performance in larger and more diverse samples, assess test-retest reliability and sensitivity to change over time, and determine how best to integrate NeuroScreen into routine HIV care for adolescents in SSA.