Agents With Potential Novel Roles as Postnatal Prophylaxis
| Agent | Potential Route and Frequency of Delivery | Advantages | Disadvantages |
|---|---|---|---|
| Available now | |||
| Dolutegravir | Oral, daily | Dispersible 5 mg tablet; broadly available with good supply chain; high resistance barrier; low toxicity. | No evidence of efficacy for prevention. Dosing for infants aged younger than 4 weeks is not yet available; infections could lead to selection of drug resistance, jeopardizing use as treatment. |
| Lamivudine | Oral, twice daily | Available in syrup and solid formulations; dosing available down from 32 weeks gestation; broadly available with good supply chain; low toxicity; demonstrated efficacy for postnatal prophylaxis. | Low barrier to resistance. |
| Lopinavir/ritonavir | Oral, twice daily | Available in liquid formulation and granules; demonstrated efficacy as postnatal prophylaxis. | Twice daily dosing is less convenient. Persistent concerns about toxicity in neonates aged younger than 14 days and premature, possibly related to vehicle of liquid formulation. |
| Abacavir | Oral, once daily | Well-tolerated in children, with fewer long-term side effects compared to zidovudine. | No evidence of efficacy as prophylaxis; evidence of long-term toxicity in adults. |
| In development pipeline | |||
| Broadly neutralizing antibodies | Intramuscular, every 1–2 months (maybe longer) | Dosing for VRCO1, VRCO1LS, and VRC07-523LS is available; new class with high barriers to resistance and separate pathway from current treatments; easy to dose across growth periods; well tolerated; no drug-drug interactions. Appeal of injections to some settings: doesn’t rely on adherence to daily oral, fewer adherence/stigma issues compared to oral medications kept at home. | Current options must be combined to optimize antiviral effects; efficacy for prevention indication still needs to be demonstrated; requires cold chain and site capacity to deliver. Biosimilar production will be a significant challenge. |
| Islatravir | Oral, monthly | Could be delivered in clinics, facilitating dose adjustments, or at home. New class with high barriers to resistance and separate pathway from current treatments. Appeal of injections to some settings: doesn’t rely on adherence to daily oral, fewer adherence/stigma issues compared to oral medications kept at home. | Drug development halted due to evidence of lymphocyte toxicity (ongoing investigation may allow continuation of the drug development program in the future). |
| Lenacapavir | Subcutaneously, every 3–6 months | As a new drug class, lower risk for interaction with maternal or infant treatment; surmounts issues of adherence to oral regimens. | May need more frequent dosing during first year of life to accommodate growth. |
| Cabotegravir | Intramuscular, once every 1–2 months | Appeal of injections to some settings: doesn’t rely on adherence to daily oral, fewer adherence/stigma issues compared to oral medications kept at home. | Pharmacokinetics will be challenging, especially for infants aged younger than 4 weeks and premature infants. Infections could lead to selection of resistance, compromising other agents like dolutegravir. Generic production will be a challenge in the immediate future. |