The HIV reservoir, which comprises diverse proviruses integrated into the genomes of infected, primarily CD4+ T cells, is the main barrier to developing an effective HIV cure. Our understanding of the genetics and dynamics of proviruses persisting within distinct CD4+ T cell subsets, however, remains incomplete. Using single-genome amplification, we characterized subgenomic proviral sequences (nef region) from naive, central memory, transitional memory, and effector memory CD4+ T cells from five HIV-infected individuals on long-term combination antiretroviral therapy (cART) and compared these to HIV RNA sequences isolated longitudinally from archived plasma collected prior to cART initiation, yielding HIV data sets spanning a median of 19.5 years (range, 10 to 20 years) per participant. We inferred a distribution of within-host phylogenies for each participant, from which we characterized proviral ages, phylogenetic diversity, and genetic compartmentalization between CD4+ T cell subsets. While three of five participants exhibited some degree of proviral compartmentalization between CD4+ T cell subsets, combined analyses revealed no evidence that any particular CD4+ T cell subset harbored the longest persisting, most genetically diverse, and/or most genetically distinctive HIV reservoir. In one participant, diverse proviruses archived within naive T cells were significantly younger than those in memory subsets, while for three other participants we observed no significant differences in proviral ages between subsets. In one participant, “old” proviruses were recovered from all subsets, and included one sequence, estimated to be 21.5 years old, that dominated (>93%) their effector memory subset. HIV eradication strategies will need to overcome within- and between-host genetic complexity of proviral landscapes, possibly via personalized approaches. IMPORTANCE The main barrier to HIV cure is the ability of a genetically diverse pool of proviruses, integrated into the genomes of infected CD4+ T cells, to persist despite long-term suppressive combination antiretroviral therapy (cART). CD4+ T cells, however, constitute a heterogeneous population due to their maturation across a developmental continuum, and the genetic “landscapes” of latent proviruses archived within them remains incompletely understood. We applied phylogenetic techniques, largely novel to HIV persistence research, to reconstruct within-host HIV evolutionary history and characterize proviral diversity in CD4+ T cell subsets in five individuals on long-term cART. Participants varied widely in terms of proviral burden, genetic diversity, and age distribution between CD4+ T cell subsets, revealing that proviral landscapes can differ between individuals and between infected cell types within an individual. Our findings expose each within-host latent reservoir as unique in its genetic complexity and support personalized strategies for HIV eradication.

Aerobic capacity is assumed to be a main predictor of workload ability and haematocrit (Hct) and haemoglobin (Hb) have been suggested as key determinants of aerobic performance. Intraspecific studies have reported increases in Hct and Hb in response to increased workload. Furthermore, Hct and Hb vary markedly among individuals and throughout the annual cycle in free-living birds and it has been suggested that this variation reflects adaptive modulation of these traits to meet seasonal changes in energy demands. We used a comparative dataset of haematological traits, measures of metabolic rate (57 species), and life-history traits (160 species) to test several hypotheses for adaptive variation in haematology in relation to migration and altitude. We then extended these general ideas to test relationships between Hct and basal metabolic rate, daily energy expenditure and activity energy expenditure, using the 57 species that we have metabolic rate information for. We found that at the interspecific level, full migrants have higher Hct and Hb than partial migrants and non-migrants, and that altitude is positively correlated with Hb but not Hct. Hct is positively associated with activity energy expenditure (energy spent specifically on costly activities), suggesting that haematological traits could be adaptively modulated based on life-history traits and that Hct is a potential physiological mediator of energetic constraint.

HIV therapy is lifelong because integrated, replication-competent viral copies persist within long-lived cells. To cure HIV, we need to understand when these viral reservoirs form, how large and genetically diverse they are, and how long they endure.

Pediatric human immunodeficiency virus (HIV) care in resource-limited settings remains a major challenge to achieving global HIV treatment and virologic suppression targets, in part because the administration of combination antiretroviral therapies (cART) is inherently complex in this population and because viral load and drug resistance genotyping are not routinely available in these settings. Children may also be at elevated risk of transmission of drug-resistant HIV as a result of suboptimal antiretroviral administration for prevention of mother-to-child transmission. We investigated the prevalence and the correlates of pretreatment HIV drug resistance (PDR) among HIV-infected, cART-naive children in Ethiopia. We observed an overall PDR rate of 14%, where all cases featured resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs): ~9% of participants harbored resistance solely to NNRTIs while ~5% harbored resistance to both NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs). No resistance to protease inhibitors was observed. No sociodemographic or clinical parameters were significantly associated with PDR, though limited statistical power is noted. The relatively high (14%) rate of NNRTI resistance in cART-naive children supports the use of non-NNRTI-based regimens in first-line pediatric treatment in Ethiopia and underscores the urgent need for access to additional antiretroviral classes in resource-limited settings.

Foraging at elevated rates to provision offspring is thought to be an energetically costly activity and it has been suggested that there are potentially physiological costs associated with the high workload involved. However, for the most part evidence for costs of increased foraging and/or reproductive effort is weak. Furthermore, despite some experimental evidence demonstrating negative effects of increased foraging and parental effort, the physiological mechanisms underlying costs associated with high workload remain poorly understood. To examine how high workload affects hematology, oxidative stress and reproductive output, we experimentally manipulated foraging effort in captive zebra finches, Taeniopygia guttata, using a previously described technique, and allowed individuals to breed first in low foraging effort conditions, and then in high foraging effort conditions. We found that birds up-regulated hematocrit and hemoglobin in response to training. Birds subjected to increased workload during reproduction had lower fecundity, although final reproductive output was not significantly different than that of controls. Offspring of parents subjected to high workload during reproduction also had higher oxidative stress when they were 90 d of age. Total antioxidant capacity and reactive oxygen metabolites of birds responded differently in the two breeding attempts, but we did detect an overall increase in oxidative stress in response to training in either attempt, which could explain the lower fecundity observed in birds subjected to increased workload during reproduction.