Are the KIR3DS1homozygous and KIR3DL1*h/*y+HLA-B*57 genotypes associated protection from HIV by different routes of exposure?
Bibliographic record
Abstract
We previously reported that HIV Exposed Seronegative (HESN) individuals have a higher frequency than HIV infected subjects of 2 genotypes: homozygosity for Killer Immunoglobulin-like Receptor (KIR) 3DS1 (KIR3DS1hmz) and homozygosity for high expression KIR3DL1 genotypes co-expressed with HLA-B*57 (*h/*y+B*57). KIR3DL1/S1 are Natural Killer (NK) cell receptors that influence NK functionality. Here, we assessed whether these genotypes were associated with protection by parenteral and mucosal routes of HIV exposure. 473 Caucasian individuals were typed for HLA, KIR3DL1/S1 generic genotypes and KIR3DL1 allotypes. Of 88 HESN, n=69 were injection drug users (IDU) and 19 were sexually exposed (sHESN). Of 385 HIV seropositive subjects n=108 were IDU and n=277 were infected through sexual exposure. The frequency of KIR3DS1hmz and *h/*y+B*57 carriers was compared in HESN versus HIV susceptible subjects exposed through parenteral versus mucosal routes. KIR3DS1hmz were more frequent among HESN than HIV positive IDU (10% versus 2.7%, respectively, p=0.05). This genotype was also more frequent among HESN than HIV infected individuals exposed sexually (25% versus 5.7%, respectively, p<0.01). The *h/*y+B*57 genotype was more frequent among HESN than HIV positive IDU (7.2 vs. 0%, respectively, p<0.01). This genotype was not observed among any sHESN and was detected in 1.8% of mucosally HIV infected individuals (p=not significant). The protective HESN KIR3DS1hmz genotype is associated with protection from HIV infection by both mucosal and parenteral routes. *h/*y+B*57 carriers are more frequent among IDU HESN than HIV susceptible subjects suggesting a protective effect via exposure by this route. Although there is no evidence that the *h/*y+B*57 genotype is protective at the level of sexual exposure the small number of sHESN precludes making firm conclusions on this point. Carriage of both these genotypes is linked to potency of NK cell function, which may influence early innate responses to HIV.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".