Introduction
Antiretroviral therapy and OI treatment
Materials and methods
Results/Guidelines
Immune reconstitution inflammatory syndrome
Management, treatment, and prophylaxis
Pneumocystis jiroveci pneumonia
Treatment
Prophylaxis
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy | Duration: at least 21 days | |
First choice with moderate/severe PcP | TMP/SMX | TMP 15–20 mg per kg/day (+SMX 75–100 mg per kg/day) applied in 3–4 daily doses (4 × 2 g or 3 × 2,5 g i.v.) Prednisone 50–100 mg (approx. 1 mg/kg for 5–10 days), e.g. 3 days 80 mg, 3 days 40 mg, 3 days 20 mg |
Mild PcP | TMP/SMX | 3 × 3 tbl. à 960 mg p.o. |
Alternatives | Pentamidine | 4 mg/kg i.v. 5 days, then reduction if necessary to 2 mg/kg (blood sugar controls!) |
Atovaquone | 2 × 750 mg (5 ml) suspension p.o. with food | |
Clindamycin + Primaquine | (3–)4 × 600 mg i.v. or p.o. + primaquine 30 mg p.o. qd | |
Dapsoneb + Trimethoprim | Dapsone 1 × 100 mg qd, trimethoprim 5 mg/kg 3 × daily | |
Prophylaxis | <200 CD4 T-cells/μl, preceding PCP episode Prophylaxis can be discontinued after successful immune reconstitution to ≥200 CD4 T-cells/μl for at least 3 months | |
First choice | TMP/SMX | 1 × 480 mg p.o. qd or 960 mg p.o. 3×/week |
Alternatives | Pentamidine | 300 mg 1–2×/month via inhalation |
Dapsone | 1 × 100 mg p.o. qd | |
Dapsone + Pyrimethamine | 1 × 50 mg qd plus pyrimethamine 1 × 50 mg/week + folinic acid 1 × 30 mg/week | |
Atovaquone | 2 × 750 mg p.o. |
Cerebral toxoplasmosis
Treatment
Prophylaxis
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Exposure prophylaxis: Immunoglobulin G (IgG)-negative patients should avoid eating raw or undercooked meat. An increased risk due to proximity to cats has not been proven [66]. Stricter measures of hygiene should be followed. However, the importance of this recommendation under effective ART is questionable.
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Primary prophylaxis: IgG-positive patients with <100 CD4 T-cells/μl require primary prophylaxis. The drug regimen of choice is TMP/SMX. In cases of allergy, desensitization may be considered [40]. See above for alternatives. Primary prophylaxis can be discontinued if CD4 T-cell count is >200 cells/μl for at least 3 months.
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Secondary prophylaxis: In the absence of immune reconstitution, patients require lifelong secondary prophylaxis, usually consisting of half the dose needed for acute therapy [67]. Clindamycin is presumably less suitable as secondary prophylaxis as it cannot cross the intact blood–brain barrier [63]. TMP/SMX also seems less effective for secondary prophylaxis. However, it may be considered because it is simple. A higher dose than that for PcP is definitely required [68, 69]. Prophylaxis may be discontinued safely if initial therapy has led to radiological resolution and if there is an immune reconstitution of >200 CD4 T-cells/μl for at least 3–6 months [31, 70‐72].
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy | Duration: at least 4 weeks | |
First choice | Sulfadiazineb + Pyrimethamine | 4 × 1–1.5 g p.o. + 2 × 50 mg p.o. (for 3 days, then 50–75 mg/d) + folinic acid 15 mg p.o. |
First choice | Clindamycin + Pyrimethamine | 4 × 600 mg i.v. (or p.o.) + 2 × 50 mg (for 3 days, then 50–75 mg/day) + folic acid 15 mg p.o. |
Alternative | TMP/SMX | 15 mg of TMP component/kg/d, in 3–4 doses a day |
Atovaquone + Pyrimethamine | 2 × 1,500 mg p.o. (with food) + 2 × 50 mg p.o. (for 3 days, then 50–75 mg qd) plus folinic acid 15 mg p.o. (CDC: loading dose 200 mg, followed by 75 mg/day) | |
Depending on findings additional dexamethasone therapy | 3–4 × 4–8 mg/day | |
Maintenance therapy/secondary prophylaxis | ||
Possible | As for acute therapy | As for acute therapy, but halve dose Discontinue if >200 CD4 T-cells/μl >6 months (if MRI is normal or without contrast enhancement) |
TMP/SMX | 1 × 960 mg p.o. | |
Alternative | Dapsone + Pyrimethamine | 50 mg p.o. qd + 50 mg p.o. qd + folinic acid 15 mg p.o. |
Primary prophylaxis (necessary only if Toxo IgG is positive) | ||
First choice | TMP/SMX | 1 × 480 mg p.o. or 960 mg p.o. 3×/week |
Alternative | Dapsone | 1 × 100 mg p.o. qd |
Alternative | Dapsone + Pyrimethamine | 1 × 50 mg p.o. qd + 1 × 50 mg/week + folinic acid 1 × 30 mg/week |
Cytomegalovirus manifestations
Treatment
Treatment of recurrences and progression during therapy:
Extraocular manifestations
Prophylaxis
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Primary prophylaxis: Gancyclovir prophylaxis for CMV retinitis with a CD4 T-cell count of <50 cells/μl is effective, but this is usually too toxic. Fundoscopy every 3 months is recommended but not necessary in the opinion of most experts (especially at a CD4 T-cell count of >100 cells/μl).
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A dose-reduced secondary prophylaxis should be initiated, preferably with oral ValGCV after about 3 weeks of acute therapy and after lesions have formed scars [87]. Discontinuation of secondary prophylaxis to avoid side effects as soon as possible is recommended and feasible [77, 100, 101]—however, not before at least 6 months of maintenance therapy and immune reconstitution at a CD4 T-cell count of >100–150 cells/μl. A small study showed that discontinuation after 18 months of ART/maintenance therapy is already safe at a CD4 T-cell count of >75/μl [101]. In the first stage after discontinuation, patients undergo an ophthalmology control at least once a month. The required duration of a recurrence prophylaxis is not clear, nor is it as yet known for how long recurrences with other organ manifestations should be monitored. Duration should therefore be handled as for CMV retinitis.
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy | Duration: at least 3 weeks | |
First choice | Gancyclovir | 2 × 5 mg/kg i.v. |
First choice | Foscarnet | 2 × 90 mg/kg i.v. |
Alternatives | Valgancyclovir | 2 × 900 mg p.o. |
Gancyclovir + Foscarnet | 2 × 5 mg/kg i.v. 2 × 90 mg/kg i.v. | |
Maintenance therapy (discontinue when CD4 T-cell count is >100–150/μl for >6 months) | ||
First choice | Valgancyclovir | 2 × 450 mg p.o |
Alternatives | Foscarnet | 1 × 120 mg/kg i.v. on 5 days/week |
Cidofovir | 1 × 5 mg/kg i.v. every 2 weeks (plus Probenecid) | |
Gancyclovir | 3 × 10 mg/kg i.v. on 3 days/week 1 × 5 mg/kg i.v. on 5 days/week | |
Primary prophylaxis | Not recommended |
Candidiasis
Treatment
Prophylaxis
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy | ||
First choice | Fluconazole | 200 mgb/100 mg 1×/day p.o. for oral candidiasis (topical therapy only in very mild cases) for 5–14 days 1 × 200 (–400) mg p.o. for esophageal candidiasis (twice the dose on the first day in each case) for 10–14 days If Fluconazole not tolerated p.o., it might be given i.v. |
Alternatives (in moderate cases) | Amphotericin | Suspension 4 × 1 ml (100 mg) up to 48 h after symptoms resolve |
Nystatin | 4 × 1 ml (100,000 I.E.) up to 48 h after symptoms resolve | |
Alternatives in case of fluconazole intolerance | Itraconazole | 400 mg loading days 1-3b/then 100–200 mg 2×/day p.o. (only as suspension due to poor bio-availability of capsules) |
Posaconazole | 400 mg 2×/day p.o. (suspension) | |
Voriconazole | 400 mgb/200 mg 2×/day p.o. | |
Alternatives for Azole failure | Anidulafungin | 200 mgb/100 mg 1×/day i.v. |
Caspofungin | 70 mgb/50 mg 1×/day i.v. | |
Micafungin | 150 mg 1×/day i.v. | |
Prophylaxis | ||
Primary prophylaxis | Not recommended | |
Secondary prophylaxis | In individual cases, generally not recommended | |
Amphotericin | Suspension 4×1 ml/day p.o. (100 mg) | |
Fluconazole | If necessary 50 mg every 48 h or 150 mg 1×/week |
Herpes simplex infections
Treatment
Prophylaxis
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy (duration: 7–10 days), daily doses | ||
First choice | Acyclovir | (3–) 5 × 400 mg p.o. |
Severe cases | 3 × 5–10 mg/kg i.v. 5 × 800 mg p.o. | |
Alternatives | Valacyclovir | 2–3 × 1,000 mg or 3 × 500–1,000 mg (expert opinion) |
Therapy for recurrent Herpes simplex infection virus episodes | Acyclovir | 3 × 400 mg p.o. for 5–10 days |
Valacyclovir | 2 × 1,000 mg for 5–10 days | |
Famciclovir | 2 × 500 mg for 5–10 days | |
Long-term prophylaxis (duration: at least 90 days) | Acyclovir | 2–3 × 400–800 mg |
Valacyclovir | 2 × 500 mg | |
Famciclovir | 2 × 500 mg |
Varicella zoster infections
Treatment
Prophylaxis
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy (duration: at least 7 days) | ||
First choice | Acyclovir | 5 × 800 mg p.o. |
First choice | Valacyclovir | 3 × 1,000 mg p.o. |
Alternatives | Famcyclovir | 3 × 500 mg p.o. |
Brivudineb
| 1 × 125 mg p.o. | |
Severe cases | Acyclovir | 3 × 10–15 mg/kg i.v. |
Prophylaxis | Not recommended |
Progressive multifocal leukoencephalopathy
Treatment
Prophylaxis
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy | ||
First choice | ART | The most important goal is maximal HIV suppression and immune reconstitution. Use intracerebral penetrating agents |
Experimental | Only in clinical trials | |
Prophylaxis | Not available |
Cryptosporidiosis
Treatment
Prophylaxis
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy | ||
Symptomatic | Loperamide Opium tincture | 2–6 × 2 mg p.o Opium tincture 1 % = 4 × 5–15 drops |
Symptomatic | Octreotide | 2–3 × 50 μg s.c. (increase dose slowly) |
Curative attempt | Nitazoxanide | 2 × 500 mg |
Curative attempt | Rifaximin | 2 × 400 mg |
Prophylaxis | Exposure prophylaxis |
Cryptococcal infections
Treatment
Prophylaxis
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy | ||
Induction therapy (treat at least 2 weeks before switch/de-escalation) | ||
First choice | Amphotericin B + flucytosine | 1 × 0.7 mg/kg/day i.v. or liposomal Amphotericin B (AmBisome®) 1 × 3–4 mg/kg/day i.v. + Ancotil® 4 × 25 mg/kg/day i.v./p.o. or 100 mg/day distributed in four separate doses |
De-escalation with good response (at least after 2 weeks) | ||
First choice | Fluconazole | 1 × 400 mg p.o. (For at least 8 more weeks) |
Alternatives | Itraconazole | 2 × 200 mg p.o. (For at least 8 more weeks) |
Primary prophylaxis | Not recommended in Germany | |
Secondary prophylaxis | Fluconazole | 200 mg/day p.o. |
Discontinuation is possible when CD4 T-cell count is >100 cells /μl and HIV-RNA below detection limit for a period of 6 months |
Infections of nontuberculous mycobacteria
Treatment
Prophylaxis
Therapy/prophylaxis | Drug | Therapeutic regimen |
---|---|---|
Acute therapy (over 1–2 months) | ||
First choice | Clarithromycin + Ethambutol + (± Rifabutin) | 2 × 500 mg p.o. + 1 × 15 mg/kg body weight p.o. + 1 × 300 mg p.o.b
|
Alternative | Azithromycin + Ethambutol + (±Rifabutin) | 1 × 500 mg p.o. + 1 × 15 mg/kg body weight p.o. + 1 × 300 mg p.o.b
|
Maintenance therapy (until CD4 T-cell count >100 cells/μl for >6 months) | ||
As for acute therapy, but without rifabutin | ||
Primary prophylaxis | ||
Not recommended | ||
Secondary prophylaxis after treated MAI-infection (start if CD4 T-cell count persists at <50/μl; discontinue if CD4 T-cells >100/μl at >6 months) | ||
First choice | Azithromycin | 1 × 1,200 mg/week p.o. |
Alternative | Clarithromycin | 2 × 500 mg p.o. |
Tuberculosis
Treatment
Adverse events
ART and TB therapy
Drug | Antiretroviral dosage adjustment | Rifabutin dosage adjustment |
---|---|---|
Boosted protease inhibitors (LPV/r, FPV/r, DRV/r, SQV/r, ATV/r) | None | 150 mg every 2 days (or 3×/week) |
Efavirenz | None | 450 mg/day |
Nevirapine | None, but cave hepatotoxicity | |
Delavirdine, etravirine | Should not be co-administered | |
Maraviroc | Depending on other antiretroviral drugs | Standard dosage |
Raltegravir | No data | No data |
Nucleoside reverse-transcriptase inhibitors (NRTIs) | None | Standard dosage |
Drug | Antiretroviral dosage adjustment | Rifampicin dosage adjustment |
---|---|---|
Efavirenz | 600 mg (800 mg for patients >60 kg | None |
Nevirapine | Should not be co-administered | |
Etravirine | Should not be co-administered | |
Maraviroc | 600 mg every 12 h | None |
Raltegravir | 800 mg every 12 h | None, TDM if possible as RAL levels decrease by 61 %. |
NRTIs | None; NRTI combination only is not recommended |