CLINICAL CASE COMORBIDITIES IN PLHIVRoger Paredes, MD, PhDInfectious Diseases Unit, irsiCaixa AIDS Research InstituteHospital Universitari Germans Trias i PujolBadalona, Catalonia, Spain

Roberto• Male, 64 years-old• Professor of History in the University of Barcelona• Born in Buenos Aires, lives in downtown Barcelona with his male

partner • They have been together for more than 20 years, but in an open

relationship • Frequent travel to South East Asia, but last trip 2 years ago• Smokes 15 cigarretes/day since he was 14-years old up to 25/day

during exams. 2 unsuccessful attempts to quit, last one 10 years ago• Occasionally, Malt whiskey after lunch

• Admitted to our hospital’s emergency department for severe pain and functional impotence in the left lower extremity after an accidental fall while we was walking down Passeig de Gràcia

Clinical exam

• What is the most likely diagnosis?1. Left knee fracture2. Left hip fracture 3. Left ankle fracture4. Left mid tibial fracture5. Come on… he’s just pretending

Clinical exam• X-Ray: left transcervical femoral neck fracture

Risk factors • Decreased bone density• Decreased muscle mass• Sex: 70% in women• Fall: Any reason witch can make you fall• Medications: cortisone• Nutrition: low calcium & vitamin D • Eating disorders like anorexia and bulimia• Age: 90% in > 70 years old• Alcohol and tobacco• Endocrine disorders • Low physical activity• Stroke & Parkinson’s disease

Admitted to trauma• X-Ray: left transcervical femoral neck fracture

Admitted to traumaSurgical

repairment

In trauma• Favorable surgical evolution • During hospital admission, a first-year resident notes the

following lesions in the left arm and mouth:

• A skin biopsy confirms Kaposi’s Sarcoma

In trauma• HIV-1 Serology +• HIV-1 RNA: 125.000 copies/mL• CD4+ T-cell counts: 214 cells/mm3 (14%)• HLA B57*01: negative• Genotype (Sanger): Wildtype

• HAV +, HBV neg, HCV neg• RPR + 1/64, FTA+

• Normal TG, Cholesterol • Total: 250 mg/dL, • LDL: 140 mg/dL• HDL: 40 mg/dL

• Body TC: Normal

Treatment Considerations for KSTumor Characteristics HIV Status Treatment Recommendations*

Minimal, nonprogressive mucocutaneous disease

Viral load undetectable Consider local interventions including radiation therapyConsider interferon or enrollment in clinical trial

Viral load detectable

Maximize antiretroviral therapyConsider local interventionsConsider interferonConsider enrollment in clinical trial

Extensive mucocutaneous without edema or KS-related symptoms

Viral load undetectable Interferon; consider chemotherapyConsider enrollment in clinical trial

Viral load detectable Maximize antiretroviral therapyConsider interferon, cytotoxic chemotherapy, or enrollment in clinical trial

Symptomatic mucocutaneous disease Any viral load Cytotoxic chemotherapy

Symptomatic visceral disease or pulmonary disease Any viral load Cytotoxic chemotherapy

Refractory disease or severe comorbid conditions Any viral load Consider local interventions for palliation

Consider chemotherapy or enrollment in clinical trial

Treatment Considerations for KSTumor Characteristics HIV Status Treatment Recommendations*

Minimal, nonprogressive mucocutaneous disease

Viral load undetectable Consider local interventions including radiation therapyConsider interferon or enrollment in clinical trial

Viral load detectable

Maximize antiretroviral therapyConsider local interventionsConsider interferonConsider enrollment in clinical trial

Extensive mucocutaneous without edema or KS-related symptoms

Viral load undetectable Interferon; consider chemotherapyConsider enrollment in clinical trial

Viral load detectable Maximize antiretroviral therapyConsider interferon, cytotoxic chemotherapy, or enrollment in clinical trial

Symptomatic mucocutaneous disease Any viral load Cytotoxic chemotherapy

Symptomatic visceral disease or pulmonary disease Any viral load Cytotoxic chemotherapy

Refractory disease or severe comorbid conditions Any viral load Consider local interventions for palliation

Consider chemotherapy or enrollment in clinical trial

ART initiation: START trial

INSIGHT-START Study Group NEJM 2015

ELV/cobi/TDF/FTC• During the following 6 months

• Fast HIV-1 RNA decline to <50 c/mL• CD4+ counts increase to >350 cells/mm3• KS lesions resolve• Rehab & physiotherapy OK

• NSAIDS for leg pain• Back home• Back to classes • Walks with a cane• Smokes 20 cig/day

NSAIDs & Antiacids• Complains of epigastric pain and still needs NSAIDs.

What can you do?

1. Give him omeprazol with no changes in his ART regimen2. Give him omeprazol minimum 2h after or 6h before his ART3. Give him antacids with no changes in his ART regimen4. Change his ART to DRVr+TDF/FTC and then hive him

omeprazol5. Tell him to be tough and stop moaning

Accelerated aging• He gets better, 2 year follow-up

• VL still <50 c/mL, CD4+ counts 550 cells/mm3, • However, Total Cholest = 220 mg/dL, LDLc =110 mg/dL, HDLc = 50 mg/dL• Smokes 10-15 cig/day. • C-Reactive Protein 35 IU• BMI index 29

• What single medical intervention will have the greatest impact on his life expectancy?

1. Intensify diet and start on statins2. Initiate ACE Antagonists3. Quit smoking4. Treat him with sevelamer5. Modify his microbiome

Smoking kills

Smoking kills

Smoking kills• Smoking cessation by 10%–25% of HIV-infected smokers

could save approximately 106 000–265 000 years of life.

• HIV-infected US smokers aged 40 years lose >6 years of life expectancy from smoking, possibly outweighing the loss from HIV infection itself.

• Smoking cessation should become a priority in HIV treatment programs.

Reddy, JID 2016

Lipids• He quits smoking!!!!!

• However, Total Cholest = 234 mg/dL, LDLc =124 mg/dL, HDLc = 48 mg/dL• BMI index 29 32• Develops criteria for type 2 diabetes

• In addition to diet and exercise, which statin would be preferable if you keep him on the same ART?

1. Simvastatin2. Atorvastatin3. Pravastatin4. Rosuvastatin5. If he is switched to DTG, he could receive Simvastatin6. 4 and 5

Liverpool HIV Interactions• Coadministration between atorvastatin and elvitegravir/cobicistat (150/150 mg once daily) has not been studied.

Atorvastatin is metabolized by CYP3A4. Coadministration with elvitegravir/cobicistat could potentially increase atorvastatin concentrations. If the use of atorvastatin is considered strictly necessary, start with the lowest dose of atorvastatin and titrate carefully while monitoring for safety. Emtricitabine and tenofovir-DF do not interact with this metabolic pathway.

• Coadministration of rosuvastatin (10 mg single dose) and elvitegravir/cobicistat (150/150 mg once daily) decreased elvitegravir Cmax and Cmin by 6% and 2%, and increased AUC by 2% (n=10). Rosuvastatin AUC and Cmax increased by 38% and 89%, respectively. The increase in rosuvastatin exposure is transient and not considered clinically relevant. Dose modifications are not necessary when rosuvastatin is administered in combination with Stribild.

• Coadministration of simvastatin and DTG has not been studied but based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Simvastatin is metabolized by CYP3A4, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Diabetes• After 6 months on

Rosuvastatin• Total Cholest = 201 mg/dL,

LDLc =101 mg/dL, HDLc = 53 mg/dL

• BMI index 32• Begins metformin up to 850

mg BID

• Which of these ARVs interacts with metformin?1. Elvitegravir2. Cobicistat3. TDF4. Dolutegravir5. Darunavir/r

Diabetes Cobicistat

Dolutegravir

• Increased metformin Cmax and AUC

• DTG QD: 66% and 79%, • DTG BID: 111% and 145%.

• US Prescribing Information suggests total daily dose of metformin to 1000 mg.

• Monitoring renal function and blood glucose

• Increased risk for lactic acidosis in moderate renal impairment

Fracture prevention• Improvement in HbA1c <6.5• No adverse events…. But still on TDF! • DEXA scan: T-score -2.7

• Which of these ART interventions would help prevent further fractures?

1. Switch to TAF/FTC/ELV/cobi 2. Switch to ABC/3TC/DTG3. Switch to boosted-PI monotherapy4. Stop ART

TDF to ABC switch

Negredo JAC 2014

TDF to TAF switch

TAF does not impact lipids

Reducing risk of fractures

Learning points• Early ART is key• Smoking is central to accelerated aging and survival

reductions in PLHIV • Beware interactions

• Statins & ritonavir but also cobicistat Sinvastatin is OK if DTG• Metformin with DTG, but also cobicistat (uncertain clinical

significance)• Prevention of bone mineral loss may involve switch from

TDF to ABC or TAF no direct comparisons• TAF does not impact lipids • Need for comprehensive geriatric management