This document discusses several cases related to diagnosing and treating HIV infection: 1) A 24-year-old man presenting with flu-like symptoms should receive an HIV RNA test and HIV serology to diagnose acute HIV infection. 2) A newly diagnosed 35-year-old woman should start antiretroviral therapy (ART) now given her CD4 count of 400 and viral load of 35K, and receive baseline evaluations including additional lab tests and screening for comorbidities. 3) A 56-year-old man with HIV and hepatitis B should also start ART now, and could receive an integrase inhibitor-based regimen given his comorbidities to avoid potential adverse effects of protease

1. HIV-1 Infection: Diagnosis,
Introduction to Treatment and
Opportunistic Infection Prophylaxis
Uma Malhotra, MD
Infectious Disease

2.  24 year old MSM presents to the ED with flu-like
symptoms, high fevers, rash and sore-throat.
 What tests will you do?
1. HIV serology
2. Plasma HIV RNA
3. Plasma HIV RNA and HIV serology
Case #1: Diagnostic Testing

3.  Fever
 Lymphadenopathy
 Pharyngitis
 Rash
 Myalgia or arthralgia
Acute Retroviral Syndrome: Common Signs
and Symptoms
 Headache
 Nausea and vomiting
 Diarrhea
 Thrush
 Neurological symptoms

4. Acute HIV Infection: Diagnosis
 Maintain high level of suspicion in patients with high
risk behaviors and compatible presentation
 Plasma HIV RNA and HIV serology
 Low-positive HIV RNA (<10K copies/mL) may be false
positive

5. HIV Diagnostic Assays
Window Period

7.  35 year old woman recently diagnosed with HIV-1
infection at a public health clinic is referred to you for
primary care.
 What should the baseline clinical and lab evaluation
include?
Case #2: Management of the Newly
Diagnosed HIV-infected Patient

8. • Risk Behaviors
• Opportunistic Infections, Malignancies
• Co-infections: STDs, TB, hepatitis
• CD4 count and VL
• ART, Side effects and response
• Comorbidities: Psychiatric, CV Risk factors, Renal
disease, Bone disease
Baseline Evaluation: History

9.  CD4 count, viral load
 Genotypic resistance test
 CBC, renal & hepatic functions
 Glucose and lipid profile
 Hepatitis screen
 STD screen: Syphilis, GC, Chlamydia
 Skin PPD
Initial Lab Testing

10.  35 year old woman recently diagnosed with HIV-1
infection at a public health clinic is referred to you for
primary care.
 CD4 count is 400 cells/µL
 Plasma HIV-1 RNA 35K copies/ml
 When to start ART?
– A. Now
– B. Defer
Case #2: Management of the Newly
Diagnosed HIV-infected Patient

11.  Potential decreased:
– HIV-related Nephropathy
– Liver disease progression from hepatitis B or C
– Cardiovascular disease
– Malignancies: AIDS and non-AIDS defining
– Neuro-cognitive decline
– Blunted immunological response at older age
– Persistent T-cell activation
 Prevention of transmission
Balance Favors Early Therapy
Cons
Toxicities
Non-adherence
Cost

12. DHHS Guidelines on ART for HIV-Infected
Adults and Adolescents
 ART is recommended for all HIV-infected ART-naive
patients to reduce risk of disease progression and
transmission
– Strength of recommendation varies by CD4+ cell
count and risk group (perinatal, heterosexual, other)
– Patients should be ready to commit to ART and
understand benefits and risks of therapy and
importance of adherence; individual patients may
elect to defer ART

13. HIV Life Cycle and Classes of ARVs
RN
A
DN
A
HIV
Nucleus
Host
Cell
Nucleoside Analogues (NRTIs)
Non-Nucleosides (NNRTIs) Protease Inhibitors (PIs)
Reverse Transcriptase
Fusion Inhibitors
Integrase Inhibitors
Protease
Integrase

14.  Nucleoside and nucleotide RTIs (NRTI)
– Zidovudine, AZT
– Abacavir, ABC
– Lamivudine, 3TC
– Didanosine, ddI
– Stavudine, d4T
– Tenofovir, TDF
– Emtricitabine, FTC
– AZT/3TC
– AZT/3TC/ABC
– ABC/3TC
– TDF/FTC
– TAF/FTC
 CCR5 receptor blocker
– Maraviroc
 Integrase inhibitor (INSTI)
– Raltegravir, RAL
– Elvitegravir, EVG
– Dolutegravir, DTG
Non nucleoside NRTIs: (NNRTI)
• Delavirdine (DLV)
• Nevirapine, NVP
• Efavirenz, EFV
• Etravirine
• Rilpivirine
Fusion inhibitors:
• Enfuvirtide, ENF or T20
Protease inhibitors (PIs):dinavir, IDV
• Saquinavir, SQV
• Nelfinavir, NFV
• Amprenavir, APV
• Atazanavir, ATV
• Fosamprenavir, FPV
• Lopinavir/ritonavir
• Tipranavir
• Darunavir
• Darunavir/cobicistat
• Atazanavir/cobicistat
Red – combination agents
Antiretroviral Therapy:
• RPV/FTC/TAF (Odefsey)
• EVG/cobi/FTC/TAF (Genvoya)
• BIC/TAF/FTC (Biktarvy)
Single pill regimens
• EFV/FTC/TDF (Atripla)
• RPV/FTC/TDF (Complera)
• EVG/cobi/FTC/TDF (Stribild)
• DTG/ABC/3TC (Triumeq)

15. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
Updated Oct 2018
Recommended Initial Antiretroviral Therapy
Regimens in Non-Pregnant: NSTI plus 2 NRTIs
 BIC/TAF/FTC (Biktarvy) AI
– Bictegravir/Tenofovir Alafenamide/Emtricitabine
 DTG/ABC/3TC (Triumeq) AI—if HLA-B*5701 negative
– Dolutegravir/Abacavir/Lamivudine
 DTG plus TAF/FTC (Descovy) and TDF/FTC (Truvada) A1
 RAL plus tenofovir/FTC (BI for TDF/FTC, BII for TAF/FTC)

16. Customizing ART
Scenario Preferred Therapy
Kidney Disease
(eGFR < 60)
Avoid TDF
High cardiac risk Avoid ABC
HBV
Use TDF/FTC or TAF/FTC
(Less data with TAF)
Osteoporosis/
osteopenia
Avoid TDF
1Mocroft A et al, Lancet, 2016

17.  56 yo man with HIV-1 infection, CD4+ count 600
cells/µL, VL 35K presents to the clinic to establish
primary care.
 CAD, hepatitis B
 When to start treatment?
– A. Now B. Defer
 What to start?
– A. PI-based B. NNRTI-based C. II-based
Case #3: Chronically Infected Patient with
Comorbidities

18. PIs: Adverse Effects
 Metabolic complications
– Hyperlipidemia
– Lipodystrophy
 GI intolerance
 Drug-drug interactions
 Hepatotoxicity

19. NNRTIs: Adverse Effects
• Skin Rashes
• Hepatotoxicity
• Drug-drug
Interactions
 EFV: Neuropsychiatric, teratogenicity in NHP

20.  28 yo man with HIV-1 infection admitted with ETOH
withdrawal. CD4 count 300 cells/µL, VL 100K/ml
 When to start treatment?
– A. Now B. Defer
 What to start?
– A. PI-based B. NNRTI-based C. II-based
Case #4:

21. Predictors of Poor Adherence
 Active alcohol or substance abuse
 Depression
 Early disease
 Concern over side effects and lack of perceived efficacy
 Complex regimen

23. Health Care Maintenance: Immunizations:
– All inactivated vaccines are
safe.
– Hepatitis A, hepatitis B
– Pneumococcal
– Influenza
– Live vaccines including
MMR, varicella, zoster,
yellow fever are
contraindicated at CD4+
counts < 200 cells/µL.

24. Health Care Maintenance
 Pap Smears
 STD screening, baseline and
periodic
 TB screening
 Age-appropriate screening for
breast, colon, and prostate
cancer

25. Thank You