Noon conference

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