The Unites States Department of Health and Human Services (DHHS) released an update in July 2025 of their guideline, Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Today, we are taking a look at how it compares to the October 2024 version of the same guidelines to compare what was added and what was changed.
Guidelines Referenced
Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV
Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV
- Publication: October 2024
- Full Text
Major Changes and Key Takeaways (2024-2025)
The 2025 update to the HHS Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV saw a handful of adjustments and new recommendations. Some of the key changes include new recommendations regarding HSV epithelial keratitis and stroll keratitis, along with updated recommendations on pneumococcal and mpox vaccines.
The following table reflects the new and adjusted recommendations added in the 2025 update. To view the full recommendations, along with the guidelines themselves, view the full-text guidelines using the links featured above.
| Topic | 2024 | 2025 |
|---|---|---|
| Cytomegalovirus (CMV) Disease | CMV end-organ disease is best prevented by using ART to maintain CD4+ count >100 cells/mm³. | To prevent CMV end-organ disease, administer ART to maintain the CD4 count ≥100 cells/mm³. |
| Epithelial Keratitis | No recommendation. | Valacyclovir 1 g PO twice a day for 5–10 days or Acyclovir 400 mg PO 5 times a day for 5–10 days or Trifluridine eye drops: 1 drop in affected eye every 2 hours while awake (maximum nine times per day) until complete re-epithelialization, then 1 drop every 4 hours while awake (minimum five times per day) for an additional 7 days or Ganciclovir 0.15% gel: 1 drop to affected eye five times a day (every 3 hours while awake) until re-epithelialization has occurred; then 1 drop 3 times a day for an additional 7 days. Topical steroids are not recommended in the management of active epithelial keratitis. |
| Stromal Keratitis | No recommendation. | Acyclovir 400 mg PO twice a day or valacyclovir 500 mg PO once daily plus prednisolone 1% 1 drop to affected eye 6–8 times per day for at least 10 weeks followed by taper; exact course should be managed by ophthalmologist based on individual patient course. |
| HSV of the Central Nervous System | No recommendation. | HSV Meningitis (Duration 10-14 Days): For initial therapy, acyclovir 10mg/kg IV every 8 hours. After clinical improvement, change to valacyclovir 1 g PO three times a day. HSV Encephalitis (Duragion 14-21 Day): Acyclovir 10 mg/kg IV every 8 hours. Some clinicians will elect to extend the course based on clinical response and degree of immunosuppression. |
| Pneumococcal Vaccine | Administer either of the following: PCV20 (Prevnar20): 0.5 mL IM x 1; or PCV15 (Vaxneuvance): 0.5 mL IM x 1 followed by at least 8 weeks later by PPSV23 (Pneumovax): 0.5 mL IM x 1. | Administer one of the following: PCV21 (Capvaxive) 0.5 mL IM x 1; or PCV20 (Prevnar20): 0.5 mL IM x 1; or PCV15 (Vaxneuvance): 0.5 mL IM x 1 followed by at least 8 weeks later by PPSV23 (Pneumovax) 0.5 mL IM x 1. |
| Mpox Vaccine | Mpox vaccination with live nonreplicating vaccinia vaccine, sold as JYNNEOS in the United States, should be offered to all people with HIV who have potential for mpox exposure or anticipate potential exposure to mpox per CDC interim clinical considerations (BII), as well as any other people with HIV who request vaccination. JYNNEOS is the preferred vaccine before mpox exposure and is safe to use in people with HIV; administer JYNNEOS in two doses (0.1 mL ID or 0.5 mL SQ) 4 weeks (28 days) apart. If the second dose is not administered during the recommended interval, it should be administered as soon as possible. There is no need to restart or add doses to the series if there is an extended interval between doses. People who had received smallpox vaccination more than 10 years ago should still receive two doses of JYNNEOS. Administration of live replicating vaccinia vaccines (i.e., ACAM2000) to pregnant, breastfeeding, or immunocompromised individuals, including people with HIV, is contraindicated. | Modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine, sold in the United States as JYNNEOS, is the preferred vaccine before mpox exposure for people with HIV because it uses a live attenuated, non-replicating virus. Administer JYNNEOS in two doses 28 days apart either 0.5 mL subcutaneously (SQ) or 0.1 mL intradermally (ID). SQ administration is preferred for people with a history of keloids and recommended for people aged <18 years. In situations where the second dose was not administered during the recommended interval, administer a second dose as soon as possible. Restarting or adding doses to the series when an extended interval between doses occurs is not necessary. At this time, booster doses, including for people with prior mpox or who were vaccinated at CD4 counts <200 cells/mm3, are not recommended. Administration of the smallpox vaccine (ACAM2000, a live replicating vaccinia vaccine) to people with HIV is contraindicated. Available human data on JYNNEOS administered to pregnant women are limited, and the risks and benefits of JYNNEOS should be discussed with the patient using shared decision-making. If mpox vaccination is sought during pregnancy or while breastfeeding, administer JYNNEOS because it contains nonreplicating virus. |
| MenABCWY | No recommendation. | Adults may receive a single dose of pentavalent meningococcal conjugate vaccine (MenABCWY) as an alternative to separate administration of MenACWY and MenB when both vaccines would be given on the same clinic day. |
| Tecovirmat | Tecovirimat 600 mg PO every 12 hours (<120 kg) or every 8 hours (≥120 kg) for 14 days within 30 minutes of a fatty meal; or Tecovirimat 200 mg IV every 12 hours for 14 days (<120 kg) or 300 mg IV every 12 hours (≥ 120 kg), if concern exists regarding altered gastrointestinal absorption capacity, the inability to take PO, or the extent of organ systems affected by mpox. | Tecovirimat 600 mg PO every 12 hours (for weight 40 kg to <120 kg) or every 8 hours (for weight ≥120 kg) for 14 days; each dose should be taken within 30 minutes of a high-fat meal; or Tecovirimat 200 mg IV every 12 hours for 14 days (for weight 35 kg to <120 kg) or 300 mg IV every 12 hours (for weight ≥120 kg) infused over 6 hours. |
| Talaromycosis | For individuals residing in endemic areas: Preferred therapy: Itraconazole 200 mg PO once daily. Alternative Therapy: Fluconazole 400 mg PO once weekly. For individuals traveling to endemic areas: Preferred therapy: Begin itraconazole 200 mg PO once daily 3 days before travel and continue for 1 week after leaving the endemic area. Alternative therapy: Begin fluconazole 400 mg 3 days before travel, then continue 400 mg once weekly while in the area and take final dose after leaving the endemic area. | For individuals residing in hyperendemic areas: Preferred therapy: Itraconazole 200 mg PO once daily. Alternative therapy: Fluconazole 400 mg PO once weekly. For individuals traveling to hyperendemic areas: Primary prophylaxis for travelers should begin 3 days prior to travel to allow serum drug level to reach steady state and may continue for 1 week after travel. Preferred therapy: Begin itraconazole 200 mg PO once daily 3 days before travel and continue for 1 week after leaving the hyperendemic area. Alternative therapy: Begin fluconazole 400 mg PO 3 days before travel, then continue 400 mg PO once weekly while in the area and take final dose after leaving the endemic area. |
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