CD4+ Cell Count Decline Despite HIV Suppression: A Probable Didanosine–Valganciclovir Interaction
Bibliographic record
Abstract
OBJECTIVE: To describe a case of significant CD4+ cell decline despite complete viral suppression in an HIV-positive patient receiving didanosine and valganciclovir. CASE SUMMARY: A 68-year-old woman diagnosed with HIV and cytomegalovirus (CMV) enteritis (CD4+ cell count 22 cells/mm(3), viral load 88,898 [4.95 log] copies/mL) was treated with valganciclovir and began lamivudine, didanosine, and lopinavir/ritonavir. Three months later, her viral load was less than 50 copies/mL and CD4+ cell count was 317 cells/mm(3). Over the next 9 months, her viral load remained suppressed, but the CD4+ cell count declined to 83 cells/mm(3) and she experienced ongoing symptoms of didanosine toxicity. Didanosine was replaced with abacavir, leading to a complete CD4+ cell recovery and resolution of symptoms. DISCUSSION: Paradoxical declines in CD4+ cell counts have been reported in HIV-infected patients virally suppressed on tenofovir/didanosine regimens, presumably via inhibition of purine nucleoside phosphorylase (PNP) by tenofovir and enhancement of didanosine toxicity. Ganciclovir and its prodrug valganciclovir also inhibit PNP and increase didanosine concentrations; thus, a similar immunological effect with this combination is possible. This hypothesis is consistent with observations from a historic multicenter CMV retinitis study, where a negative CD4+ cell response was observed in patients receiving ganciclovir, while those treated with foscarnet experienced a CD4+ cell increase and a mortality advantage. Of the subjects who received any type of nucleoside therapy during this study, didanosine use was proportionally higher in the ganciclovir arm versus the foscarnet arm. According to the Naranjo probability scale, our patient experienced a probable adverse reaction associated with the combination of didanosine and valganciclovir. CONCLUSIONS: Patients receiving didanosine-containing highly active antiretroviral therapy and ganciclovir or valganciclovir for treatment of CMV infection should be monitored for didanosine toxicity and unexpected CD4+ cell loss or failure of CD4+ cell recovery. Reduction of didanosine dosage or substitution with an alternative antiretroviral may be necessary.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".