What are the treatment guidelines for HIV patients with low CD4 (Cluster of Differentiation 4) counts and associated opportunistic infections?

From the Guidelines

Treatment for HIV patients with low CD4 counts requires immediate initiation of antiretroviral therapy (ART) along with prophylaxis and treatment for opportunistic infections (OIs), as recommended by the 2020 guidelines of the International Antiviral Society-USA panel 1. The recommended first-line ART regimen typically includes two nucleoside reverse transcriptase inhibitors (NRTIs) such as tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), combined with an integrase strand transfer inhibitor (INSTI) like dolutegravir (50mg daily). For patients with active OIs, treatment should generally begin for the infection first, followed by ART within 2 weeks, as this approach reduces immune reconstitution inflammatory syndrome (IRIS) risk while not delaying immune recovery 1. Some key considerations for OI treatment include:

• Trimethoprim-sulfamethoxazole (TMP-SMX, 800/160mg daily) for Pneumocystis pneumonia prophylaxis when CD4 counts are below 200 cells/mm³
• Azithromycin (1200mg weekly) for Mycobacterium avium complex prevention when CD4 counts fall below 50 cells/mm³
• Fluconazole (200mg daily) for cryptococcal disease prevention in severely immunocompromised patients
• Rifampin-based regimen alongside appropriately adjusted ART for tuberculosis co-infection Regular monitoring of CD4 counts, viral load, and drug interactions is essential, as is adherence support 1. Additionally, for patients with cancer, the NCCN guidelines recommend myeloid growth factor support, gram-negative infection prophylaxis, and herpes simplex virus (HSV)/Varicella zoster virus (VZV) prophylaxis, as well as consideration of antifungal prophylaxis and hepatitis B virus (HBV) therapy 1. For patients with HBV co-infection, the EASL 2017 guidelines recommend starting antiretroviral therapy (ART) irrespective of CD4 cell count, and using a TDF- or TAF-based ART regimen 1. Overall, a comprehensive approach that addresses both HIV replication and prevents opportunistic infections is crucial for reducing morbidity and mortality in immunocompromised patients.

From the FDA Drug Label

The mean baseline CD4+ cell count was 279 cells/mm3 (range 3–956) and median baseline plasma HIV-1 RNA was 77,600 copies/mL (range 417–5,130,000). Forty-three percent of subjects had baseline viral loads >100,000 copies/mL and 39% had CD4+ cell counts <200 cells/mm3. Through 144 weeks, 11 subjects in the tenofovir disoproxil fumarate group and 9 subjects in the d4T group experienced a new CDC Class C event The mean increase from baseline in CD4+ cell count was 263 cells/mm3 for the tenofovir disoproxil fumarate arm and 283 cells/mm3 for the d4T arm Through 48 weeks, 7 subjects in the FTC + tenofovir disoproxil fumarate group and 5 subjects in the AZT/3TC group experienced a new CDC Class C event (10 and 6 subjects through 144 weeks)

Treatment Guidelines for HIV Patients with Low CD4 Counts and Associated Opportunistic Infections:

• The treatment guidelines for HIV patients with low CD4 counts and associated opportunistic infections involve the use of antiretroviral therapy (ART) to suppress the viral load and increase the CD4 cell count.
• The choice of ART regimen depends on various factors, including the patient's viral load, CD4 cell count, and medical history.
• The FDA drug label provides information on the efficacy and safety of tenofovir disoproxil fumarate in treatment-naive and treatment-experienced patients with HIV-1 infection.
• The label also provides information on the incidence of new CDC Class C events in patients treated with tenofovir disoproxil fumarate.
• Key Points:
  • Patients with low CD4 counts (<200 cells/mm3) are at higher risk of opportunistic infections.
  • ART can help increase the CD4 cell count and reduce the risk of opportunistic infections.
  • Tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor that can be used in combination with other ART agents to treat HIV-1 infection.
  • The efficacy and safety of tenofovir disoproxil fumarate have been evaluated in several clinical trials, including Trial 903 and Trial 934.
  • The label provides information on the incidence of new CDC Class C events in patients treated with tenofovir disoproxil fumarate, which can help guide treatment decisions 2.

From the Research

Treatment Guidelines for HIV Patients with Low CD4 Counts

• The treatment guidelines for HIV patients with low CD4 counts recommend starting antiretroviral therapy (ART) as soon as possible after diagnosis, regardless of the CD4 count 3, 4.
• The initial laboratory evaluation for HIV patients includes CD4+ cell count, plasma HIV-1 RNA, and testing for HIV reverse transcriptase and protease resistance mutations 3.
• Recommended starting ART regimens include ictegravir plus tenofovir alafenamide (TAF)/emtricitabine (FTC), dolutegravir (DTG) plus abacavir/lamivudine, DTG plus TAF (or TDF)/FTC, or DTG plus 3TC 3.

Associated Opportunistic Infections

• Patients with low CD4 counts are at risk of developing opportunistic infections, and ART regimens should be chosen based on the patient's individual needs and medical history 5, 6.
• Nucleoside reverse transcriptase inhibitors (NRTIs) are a common component of ART regimens, but NRTI-reducing strategies have been investigated to minimize toxicity and improve patient outcomes 5.
• Integrase strand transfer inhibitors (INSTIs) are becoming more common in HIV treatment and have been shown to effectively halt HIV-1 replication with a higher genetic barrier to resistance compared to NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) 6.

CD4 Count and Treatment Outcomes

• The CD4 count is an important indicator of immune function in HIV patients, and treatment outcomes are generally better for patients who start ART earlier, regardless of their CD4 count 4.
• Clinical trials have demonstrated benefits for starting ART at any CD4 count, and some cohort studies have shown that early therapy is associated with improved outcomes and reduced risk of transmission 4, 7.
• The choice of ART regimen should be individualized based on the patient's CD4 count, viral load, and other factors, such as resistance mutations and medical history 3, 6.