HIV TREATMENT AND OI PROPHYLAXIS
HAART
Types of Antiretrovirals:
§ Nucleoside reverse transcriptase inhibitors (NRTIs)
§ Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
§ Protease inhibitors (PIs)
Initiation:
§ Before initiating therapy, check a CBC, creat, LFTs, CD4 and viral load.
§ Initiation of HAART should be considered in the following patients:
- Those with AIDS or symptomatic HIV (eg: thrush, unexplained fevers)
- Those with asymptomatic HIV but high viral load (>35-50,000 copies/ml) or low CD4 count (consider at 200-350/mm3, definite at <200/mm3)
Regimens:
HAART regimens usually will consist of an NNRTI + 2 NRTIs or a PI + 2 NRTI. The following are recommended ARV combination regimens in Tanzania for ART naïve patients (based on National Guidelines for the Clinical Mgt of HIV/AIDS 2005)
1. Stavudine (d4t) + Lamivudine (3TC) + Nevirapine (NVP). This is the default regimen prescribed to most patients and it comes in a single pill form (Triomune). LFTs should be monitored at the start of therapy as NVP can be hepatotoxic. Alternative regimens and their indications are as follows:
2. Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine (NVP). Use this regimen if the patient has a history of peripheral neuropathy (d4T can cause neuropathy). Again, LFTs should be monitored at the initiation of therapy.
3. Stavudine (d4T) + Lamivudine (3TC) + Efavirenz (EFV) for patients with TB and a history of anemia (hgb <7.5) (AZT can cause bone marrow suppression)
4. Zidovudine (AZT) + Lamivudine (3TC) + Efavirenz (EFV) for patients with TB and no history of anemia
Monitoring:
§ Pt’s should be seen 2 weeks after initiation of HAART to check for adverse effects and to have the LFTs and CBC checked.
§ CD4 count and viral load should be checked every 6 months.
§ Treatment failure is indicated by a viral load increase of .3 to .5 logs or a 30% fall in CD4 count. Appearance of or persisting OIs may also indicate treatment failure. Consideration should be made in any of these cases to change the ARV regimen.
Prophylaxis against OIs:
§ PCP: Cotrimoxazole should be started in patients with a CD4 < 200. Dosing is one double strength tab every day.
§ Toxoplasmosis: Start prophylaxis with Clotrimoxazole when CD4 <100 (although patient should technically already be on it for PCP ppx). Dosing is also one double strength tab every day.
§ MAC: Start azithromycin 1200mg qweek in patients with a CD4 < 50
§ TB: All HIV+ patients with a positive PPD who are not on HAART and have no signs of active TB are eligible for TB preventative therapy. You must rule out active TB before starting preventative therapy to avoid drug resistance. Treatment consists of INH 5mg/kd QD + vitamin B6 x 9 months.
Treatment of Specific OI/Complications:
§ HSV: mild/moderate cases can be txd with Acyclovir 400mg po tid x 7 days. More severe cases or recurrent HSV infections should be txd with Acyclovir 800mg five times a day for 5 days.
§ VZV: Treat with Acyclovir 800mg 5 times a day for 7 days unless suspect disseminated VZV or ophthalmic nerve involvement in which case treatment should be started with IV acyclovir, 1mg/kg q8h x 7 days
§ Cryptococcal meningitis: treat with IV Amphotericin B .7mg/kg/day x 6 weeks plus Fluorocytosine 50mg/kg/day x 14 days Alternatively, you can treat with fluconazole IV 400mg/day x 10 days followed by 400mg po qd x 10 weeks. After treatment patients should then be maintained on fluconazole 200mg qd.
§ Candidiasis: Treat oropharyngeal candidiasis with fluconazole 200mg po qd x 2-3 weeks. Other drugs that can be used include miconazole nitrate, clotrimazole, nystatin oral suspension.
§ Pneumocystis pneumonia (PCP): Treat with co-trimoxazole 100-120 mg/kg/day IV/PO in 2-4 divided doses for a total of 21 days. Consider adding steroids for severe cases (prednisone 40mg po bid x 5 days followed by 40mg po qd x 5 days followed by 20mg po qd x 11 days)
§ Toxoplasma encephalitis: Treat with pyrimethamine 200mg po in divided doses on day 1, then 75-100mg po od plus sulfadiazine 1-1.5 mg po qds plus calcium folinate 305mg po every 3rd day all for at least 6 weeks. Afterwards patients should be on pyrimethamine 25-50 mg po qd and sulfadiazine .5-1g qd for life.
HIV CASE
A 32 yo F presents with a recent diagnosis of HIV. She did not follow up at the clinic where she was tested as she was frightened after she received the diagnosis. She comes to you now to initiate care.
1. What questions do you want to ask her during the history?
2. What do you want to focus on during the physical exam?
3. What labs and tests do you want to order?
You perform a detailed history and physical. She has no other medical problems and is not taking any other medications nor does she have any allergies. She does not have any children. She does not report any history of OIs. She denies any fevers, night sweats or weight loss. Her review of systems is essentially negative. Her physical exam is also benign. You order a CD4 count and viral load as well as a CBC with diff, LFTs, and creat. You obtain a baseline CXR and EKG. A PPD is also placed. You ask her to follow up with you in 1 week to go over her lab results. Her lab results return and you see that her CD4 count is 180 and a viral load of 20,000. The rest of her studies are normal including her CXR and EKG. A nurse tells you that the pt’s PPD was negative.
4. Do you want to start ARVs in the patient? If so which regimen?
5. What OI prophylaxis should you begin if any?
6. Would you want to treat this patient for latent TB? Why or why not?
The patient returns at her scheduled visit and you review her lab results with her. You tell her that you would like to begin her on HAART therapy with Stavudine (d4t) + Lamivudine (3TC) + Nevirapine (NVP). In addition you would also like to start her on PCP prophylaxis with cotrimoxazole. While you realize that the patient’s PPD may be falsely negative due to anergy from her low CD4 count you are reassured by her clear chest x-ray and decide not to treat her with INH.
7. How soon do you want to see the patient again?
8. What labs will you want to draw then?
You tell the patient to return in 2 weeks so that you can monitor her for side effects of the medications and check LFTs. Unfortunately the patient never returns to the clinic. 9 months later she is admitted to the hospital complaining of fevers and severe SOB. She states that she has not been taking her ARVs or cotrimoxazole.
9. What questions do you want to ask the patient?
10.What physical exam findings are you looking for?
The patient states that her symptoms started 1 week ago and have been progressing over the past week. She initially would become SOB after walking a block but now becomes dyspneic even when shifting around in the bed. She denies orthopnea, PND or edema. She has had a nonproductive cough with no hemoptysis. She denies any neurological complaints. She is febrile to 38.6, BP 110/65, HR 110. She is satting 95% on room air but after you have her ambulate across the room her O2 sat drops to 85. Her exam is significant for bilateral crepitations. Her nail beds have a bluish tint. Her neuro exam is normal.
11. What labs and studies do you want to order?
12. Do you want to start the patient on any medications?
You order a CBC, creat, LDH, CD4 count, EKG and CXR. You also order sputum cultures and stains for AFB and PCP. You begin the patient on empiric treatment for PCP with IV cotrimoxazole and steroids. After 2 days the patient states that she feels much better. Her labs and studies return and her CXR reveals bilateral diffuse interstitial infilatrates. Her CBC and creat are normal, LDH is 300. Her AFB is negative x 3, PCP stain is positive. The patient continues to improve and is eventually changed to an oral regimen of cotrixazole and is discharged to complete a 21 day course.
Answers
- Ask about symptoms such as fever, anorexia, weight loss, night sweats, lymphadenopathy, pruritis or rashes, cough, dysphagia/odynophagia, diarrhea, headaches, visual symptoms, seizures. Also take a sexual history & inquire about children, current sexual partners who should also be tested.
- Look for temporal wasting, fever, lymphadenopathy; skin findings such as rashes or vesicles (make sure to examine the perianal and genital area too); oral findings such as thrush or hairy leukoplakia; signs of lung consolidation or crepitations; hepatosplenomegaly; peripheral neuropathies or focal neural deficits, cognitive impairment.
- Check CD4 and viral load, also consider CBC, creat, LFTs, PPD, CXR; other diagnostic tests as history requires.
- ARVs should be started on this patient as her CD4 count is less than 350. The optimal regimen to start should be 2 NRTIs + either 1 NNRT or 1 PI. The most commonly used initial regimen in Tanzania is Stavudine (d4t) + Lamivudine (3TC) + Nevirapine (NVP). Check LFTs when beginning therapy.
- Cotrimoxazole should be started for PCP prophylaxis (CD4<200).
- There is no indication to treat the patient for latent TB as her PPD is negative & her CXR is clear. She should have a repeat PPD placed in 6 months after her CD4 has improved as there are many false negative PPDs in severely immunocompromised patients.
- See the patient 2 weeks after initiating HAART to assess for any adverse reactions to medications & to check a CBC & LFTs.
- CBC & LFTs.
- Ask to differentiate between PCP, TB, or bacterial PNA. Other possibilities include CCF & pulmonary KS. Is SOB much worse with exertion? Is cough productive? Any hemoptysis? Any recent weight loss, night sweats? Any recent TB exposure?
- Look for evidence of respiratory distress: tachypnea, hypoxia. Listen for rales on lung auscultation. Assess for evidence of volume overload/CCF.
- CXR, ECG, FBP, LDH, creatinine, sputum for bacterial culture, AFB, & PCP.
- The patient should be treated presumptively for severe PCP pneumonia with co-trimoxazole 100-120 mg/kg/day IV/PO in 2-4 divided doses for a total of 21 days + prednisone 40mg po bid x 5 days followed by 40mg po qd x 5 days followed by 20mg po qd x 11 days.
