High genetic load without purging in caribou, a diverse species at risk.

High intra-specific genetic diversity is associated with adaptive potential, which is key for resilience to global change. However, high variation may also support deleterious alleles through genetic load, thereby increasing the risk of inbreeding depression if population sizes decrease. Purging of deleterious variation has been demonstrated in some threatened species. However, less is known about the costs of declines and inbreeding in species with large population sizes and high genetic diversity even though this encompasses many species globally that are expected to undergo population declines. Caribou is a species of ecological and cultural significance in North America with a wide distribution supporting extensive phenotypic variation but with some populations undergoing significant declines resulting in their at-risk status in Canada. We assessed intra-specific genetic variation, adaptive divergence, inbreeding, and genetic load across populations with different demographic histories using an annotated chromosome-scale reference genome and 66 whole-genome sequences. We found high genetic diversity and nine phylogenomic lineages across the continent with adaptive diversification of genes, but also high genetic load among lineages. We found highly divergent levels of inbreeding across individuals, including the loss of alleles by drift but not increased purging in inbred individuals, which had more homozygous deleterious alleles. We also found comparable frequencies of homozygous deleterious alleles between lineages regardless of nucleotide diversity. Thus, further inbreeding may need to be mitigated through conservation efforts. Our results highlight the "double-edged sword" of genetic diversity that may be representative of other species atrisk affected by anthropogenic activities.

Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. DESIGN: Longitudinal study. PARTICIPANTS: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017. MEASUREMENTS: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. RESULTS: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed. CONCLUSIONS: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

Risk factors for symptomatic HIV-associated neurocognitive disorder in adults aged 50 and over attending a HIV clinic in Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorder (HAND), although prevalent, remains a poorly researched cause of morbidity particularly in sub-Saharan Africa (SSA). We aimed to explore the risk factors for HAND in people aged 50 and over under regular follow-up at a government HIV clinic in Tanzania. METHODS: HIV-positive adults aged 50 years and over were approached for recruitment at a routine HIV clinic appointment over a 4-month period. A diagnostic assessment for HAND was implemented, including a full medical/neurological assessment and a collateral history from a relative. We investigated potential risk factors using a structured questionnaire and by examination of clinic records. RESULTS: Of the cohort (n = 253), 183 (72.3%) were female and the median age was 57 years. Fifty-five individuals (21.7%) met the criteria for symptomatic HAND. Participants were at a greater risk of having symptomatic HAND if they lived alone [odds ratio (OR) = 2.566, P = .015], were illiterate (OR 3.171, P = .003) or older at the time of HIV diagnosis (OR = 1.057, P = .015). Age was correlated with symptomatic HAND in univariate, but not multivariate analysis. CONCLUSIONS: In this setting, HIV-specific factors, such as nadir CD4 count, were not related to symptomatic HAND. The "legacy theory" of early central nervous system damage prior to initiation of anti-retroviral therapy initiation may contribute, only in part, to a multifactorial aetiology of HAND in older people. Social isolation and illiteracy were associated with symptomatic HAND, suggesting greater cognitive reserve might be protective.