HIV patients
These guidelines are for adults only; please refer to the HIV guidelines for further information and information relevant to children.
HIV patients are some of the sickest patients on the ward.
First line of clerking/ ward entry should have HIV status.
It is important to know HIV status in all in patients in Malawi in Kamuzu Central hospital the status of every patient should be known.
Status will fit into three categories
· Known positive
· Known negative (tested within three months)
· Refusing testing (try to persuade to have the test, it is in their best interest)
Remember newly infected individuals can take 3 months to until their test is positive.
If positive we then wish to know…
· If they take ARV’s and for how long. It will take some time for them to have an effect this depends on the degree of immunocompromise on starting treatment.
· If they take Cotrimoxazole (CPT): this is used to prevent Pneumocystitis jiroverci pneumonia.
If patients are not taking ARV’s they need to be staged according to WHO staging this is done on the HIV related infections/conditions as so…
Stage 1:
Ø Asymptomatic patients
Ø Persistent generalized lymphadenopathy
Stage 2:
Ø Respiratory tract infections
Ø Recurrent (sinusitis, tonsillitis, otitis media, pharyngitis)
Ø Herpes zoster
Ø Angular cheilitis
Ø Oral ulcerations, recurrent
Ø Papular pruritic eruptions / Fungal nail infections
Ø Moderate weight loss <10%, unexplained
Ø Seborrhoeic dermatitis
Stage 3:
Ø Fever, persistent unexplained, intermittent or constant, >1 month
Ø Oral hairy leukoplakia
Ø Pulmonary tuberculosis (current)
Ø Tuberculosis (PTB or EPTB) within the last 2 years
Ø Anaemia, unexplained < 8 g/dl
Ø Neutropaenia, unexplained < 500 /mm3
Ø Thrombocytopaenia, chronic < 50,000 /mm3
Ø Severe weight loss >10% and/or BMI <18.5kg/m2, unexplained
Ø Diarrhoea, chronic (>1 month) unexplained
Ø Oral candidiasis
Ø Severe bacterial infections (pneumonia, empyema, pyomyositis, bone/joint, meningitis, bacteraemia)
Ø Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
Ø Hepatitis B or C infection
Stage 4:
Ø Pneumocystis pneumonia
Ø Candidiasis of oesophagus, trachea, bronchi or lungs
Ø Extrapulmonary tuberculosis
Ø Kaposi’s sarcoma
Ø HIV encephalopathy
Ø Cryptococcal meningitis or other Extrapulmonary cryptococcosis
Ø Disseminated non-tuberculous mycobacterial infection
Ø Cryptosporidiosis, chronic with diarrhoea
Ø Isosporiasis >1 month
Ø Disseminated mycosis (coccidiomycosis or histoplasmosis)
Ø Symptomatic HIV-associated nephropathy or cardiomyopathy
Ø Progressive multifocal leukoencephalopathy
Ø Cerebral or B-cell non-Hodgkin lymphoma
Ø HIV wasting syndrome (severe weight loss + persistent fever or
Ø severe weight loss + chronic diarrhoea)
Ø Bacterial pneumonia, recurrent severe
Ø Chronic herpes simplex infection (orolabial, genital / anorectal
Ø >1 month or visceral at any site)
Ø Cytomegalovirus infection (retinitis or infection of other organs)
Ø Toxoplasmosis of the brain
Ø Non-typhoidal Salmonella bacteraemia, recurrent
Ø Invasive cancer of cervix
Ø Leishmaniasis, atypical disseminated
Cotrimoxoazole therapy (CPT)
This drug is used in all HIV positive adults to prevent PCP pneumonia, diarrhoea, malaria and other HIV related diseases.
It is given as 480mg BD for life. Contraindications to CPT are…
· Jaundice
· Renal failure
· Developing Stevens-Johnson syndrome
· Pregnant women cannot take within 14 days of taking Sulfadoxine/Pyrimethamine
Starting Antiretroviral therapy
After staging anyone who is found to be stage 3 or 4 should be referred to start ARV therapy. In addition ARVs should be given to all patients who are pregnant or breast feeding. CD4 count is measured in patients who are unwell and do not meet stage 3/4 criteria, if the CD4 count is ≤ 350cells/mm3 then the patient is eligible for ARV therapy.
ARV therapy
ART requires combining 3 different ARVs that act differently in order to avoid development
of drug‐resistant HIV. If possible try to keep the patient on a first line regime
1st line regimens:
Are easy to prescribe and easy to take, have a low risk of side effects and require no lab monitoring for toxicity.
There are 6 different 1st line regimens if a patient has a significant side effect switch them to an alternative 1st line regimen without delay. Alternative regimens are chosen by substituting only the ARV responsible for the side effects.
2nd Line regimens:
These are a lifeline for patients who have confirmed treatment failure on 1st line
regimen (usually due to poor adherence in the past). Moving from 1st to 2nd line ART is called
switching.
2nd line regimes
o Contain a completely different class of ARVs (proteinase inhibitors)
o Are more complicated to prescribe and take
o Can have more side effects
o There are 3 different 2nd line regimens. The appropriate 2nd line regimen is
determined by the 1st line regimen that the patient was taking when failing.
3rd Line regimens:
These are ‘salvage therapy’ and a last resort for patients failing on second line in
spite of good adherence. This requires confirmation of drug resistant virus using genetic
analysis in the lab. 3rd line can currently only be initiated on a study basis by a specialised
expert ARV clinician.
3rd line regimes
o Very expensive
o Can have more side effects and be difficult to take
Abbreviations of ARV’s
3TC Lamivudine
ABC Abacavir
AZT Zidovudine
d4T Stavudine
ddl Didanosine
EFV Efavirenz
LPV/r Liponivir/ritonavir
NVP Nevirapine
TDF Tenofivir
ZDV Zidovudine
Classification of ARVs
ARVs are classified according to their action…
Nucleoside reverse transcriptase inhibitors include: stavudine (d4T), zidovudine (AZT), abacavir (ABC), lamivudine (3TC) and tenofivir (TDF).
Non-nucleoside reverse transcriptase inhibitors include: nevirapine (NVP) and efavirenz (EFV).
Protease inhibitors are liponivir and ritonavir (LPV/r).
Regimes for ARVs
Standard ARVs 1st line (Regimen 1 ‐ 6) and 2nd Line (Regimen 7 ‐ 9)
Regime 1
d4T 30mg /3TC 150mg /NVP 200mg
Indication
This is first line therapy except for those breast feeding, pregnant or already on TB therapy.
This regime is started with a starter pack (gradual increase in drugs).
Contraindications to regime 1: Jaundice / hepatitis
Side effects: Switch to regime:
Neuropathy 2 5, 6, NS
Hepatitis/ Skin rash 3
Lipodystrophy 5
Lactic acidosis 5 NS
Treatment failure 7 9
Regime 2
AZT 300mg / 3TC 150mg / NVP 200mg
This is standard for children under 15 years of age.
This regime is started with a starter pack
Contraindications to regime 2: Anaemia <8g/dl, Jaundice / hepatitis
Side effects: Switch to regime:
Anaemia 1 5, 6
Hepatitis/ Skin rash 4 3
Lipodystrophy 5
Lactic acidosis 5 NS
Treatment failure 7 9
Regime 3
d4T 30mg / 3TC 150mg/EFV 600mg
Contraindications: History of psychiatric illness
Side effects: Switch to regime:
Neuropathy 2 5, 6, NS
Hepatitis/Skin rash 6
Psychiatric disorder 1 NS
Lipodystrophy 5
Lactic acidosis 5
Treatment failure 7
Regime 4
AZT 300 mg /3TC 150mg /EFV 600mg
Contraindications: History of psychiatric illness, Anaemia <8g/dl
Side effects: Switch to regime:
Anaemia 3 5
Lipodystrophy 5
Lactic acidosis 5 9
Hepatitis/ Skin rash 6
Psychiatric disorder 2 NS
Treatment failure 7 9
Regime 5
TDF 300mg /3TC 300mg /EFV 600mg
This regime is 1st choice for pregnant women, breastfeeding women and adults already on TB
Treatment.
Contraindications: History of psychiatric illness, Renal failure, Child under 12 years
Side effects: Switch to regime:
Renal failure lower dose or 2
Hepatitis/ Skin rash 6
Psychiatric disorder 6 NS
Treatment failure 8
Regime 6
TDF 300mg / 3TC 300mg/NVP 200mg
This regime starts with a starter pack.
Contraindications: Jaundice/Hepatitis, Renal failure, Child under 12 years
Side effects: Switch to regime:
Renal failure lower dose or 2
Hepatitis/ Skin rash 5 NS
Treatment failure 8
Regime 7
TDF 300mg / 3TC 300mg/ LPV/r 200/50
Contraindications: Renal failure, Child under 12 years
Side effects: Switch to regime:
Renal failure 8
Nausea, vomiting NS
Regime 8
AZT 300mg / 3TC 150mg /LPV/r 200/50
Contraindications: Anaemia <8g/dl
Side effects: Switch to regime:
Anaemia 7
Nausea, vomiting NS
Conditions where different ARVs may be needed
Anaemia (<8g/dl)
Treatment can be started within 7 days of diagnosis with d4T/3TC/NVP
Active TB
Treatment should be started within 14 days of diagnosis
TB treatment + ARVs can be started on the same day if the patient is stable
Don’t delay either TBT or ARVs
Treatment: AZT/3TC/EFV or TDF/3TC/EFV
Jaundice
Refer to District or Central Hospital
Start ARVs after investigation and stabilisation
Treatment: d4T/3TC/EFV
1st trimester pregnancy
Start ARVs in the 2nd trimester with TDF/3TC/EFV
In labour (new HIV diagnosis)
Start ARVs as soon as possible with TDF/3TC/EFV
Renal failure
Refer to District or Central Hospital
Start treatment within 7 days of diagnosis with AZT/3TC/EFV
Monitoring ARVs
ARVs should be switched if there is no improvement in CD4 count or patient condition after 2 months of starting ARV therapy. ARVs should also be switched if the patient deteriorates and CD4 count drops despite good compliance.
Serious side effects of ARVs
Patients should be told to stop ARVs and present to hospital immediately if they develop any of the following symptoms…
Ø Yellow eyes/ skin
Ø Severe abdominal pain and vomiting
Ø Shortness of breath
Ø Blistering skin rash involving eyes, genitals or mouth
Common complications of ARV treatment
Lactic acidosis
This severe life threatening condition occurs most commonly with stavudine (d4T) and didanosine (ddI), though also with patients on zidovudine (AZT), abacavir and lamivudine (3TC). It is more likely to occur in female patients and those who are pregnant or obese.
Symptoms of lactic acidosis include fatigue, stomach pain, nausea, vomiting and shortness of breath, though symptoms can come on gradually. When assessing these patients increased respiratory rate and tachycardia are early signs.
The diagnosis is made by measuring the pH of the blood and the lactate level though this is not always possible in Malawi. A pH <7.35 or lactate > 5 mmol/L indicates a poor prognosis. Individuals without any signs or symptoms may have asymptomatic hyperlactaemia in which it may be simply appropriate to switch ARVs.
Treating lactic acidosis involves stopping all ARVs and giving IV fluids at 3 litres a day minimum until symptoms settle.
Jaundice/ Hepatotoxicity
This is more common in those with pre-existing liver damage (Hepatitis B,C, alcoholics), renal failure or those on protease inhibitor therapy.
Severe hepatotoxicity can occur with Nevirapine (NVP) but also with efavarenz (EFV) and abacivir.
When treating these patients the ARVs must be stopped and other causes looked for (alcohol, Gall stones etc). Treating what is found appropriately.
Stevens-johnsons syndrome
This is a blistering skin rash present on most of the surfaces of the skin and involving the mouth, eyes and genitals. This condition can be caused by other illnesses such as streptococcal infection or diabetic drugs. The common cause in Malawi is due to Nervirapine (NVP) therapy though cotrimoxazole (CPT) can also cause this condition.
To treat Stevens-Johnson syndrome stop all ARV treatment, ensure the patient is fully hydrated with good urine output, (usually given IV fluid at least 3L per day). Antibiotics such as cefuroxime1g bd are given to cover skin infection and the eyes are covered with tetracycline eye ointment. Potassium per manganite soaks are also prescribed to prevent skin infection.
Immune reconstitution syndrome (IRS)
This is caused when the immune system becomes over-aggressive as it recovers due to ARVs and attacks an already existing infection. This usually occurs within days to week of starting ARVs. Often immune reconstitution syndrome can unmask a previously unknown infection or worsen a disease that was improving.
Common infections in IRS
Ø TB
Ø Kaposi sarcoma
Ø Cryptococcal Meningitis
Ø Herpes zoster
Ø Hepatitis
Treat the underlying infection and continue the ARVs.
Psychiatric disorders
Efavirenz (EFV) can cause a range of psychiatric disorders from insomnia to severe dellusions this is especially likely if there is pre-existing psychiatric disorder. It should be withdrawn in people with psychiatric disorders. Abacavir and lamivudine(3TC) should also be avoided in people with psychiatric disorders.
Peripheral Neuropathy
This is a common side effect of Stavudine (d4T), didanosine (ddI) and zidovudine (AZT). The patient will complain of numbness from the feet upwards, they should have their ARV regime switched.
HIV related illness
Skin and mucosal problems
Dermatophytes
This is a fungal rash usually found on hairy or sweaty regions of the skin such as the groin, axilla, scalp and face. This condition can occur in non-reactive patients but is more common in HIV.
The rash is often itchy, greasy and scaly. It is treated with an antifungal cream such as clotrioxazole or miconazole in the first line and with ketoconazole tablets 200mg BD 7days if these are ineffective.
Candida oral/oesophageal
This presents with white/red plaques anywhere in the mouth cavity. Oesophageal candidiasis will cause pain and difficulty swallowing (dysphagia).
Oral candidiasis may be treated first patients treat with nystatin solution 4ml QID for 10-14 days. If there is persistent candidiasis or a suggestion of oesophageal candidiasis then fluconazole 200mg for 14 days should be given.
Herpes Zoster
Chicken pox is primary disease causing widespread vesicular rash.
Can remerge as shingles in immunocompromised, this follows a dermatomal distribution (doesn’t cross the patients midline) and begins with pain followed by the rash.
Look for secondary infection especially if it involves the eyes. The shingles is caught before the blisters burst then acyclovir 800mg 5 times a day for 7 days can improve symptoms.
Tinea corporis, cruris, pedis
Round red plaques with a scaly edge on the body, head or feet but may be widespread across the body.
Treat with Whitfield’s ointment, Gentian-violet paint or clo-trimazole cream twice daily for 3-4 weeks. Griseosulfin tablets 500mg bd for 3-4 weeks can be used as second line if no response.
Neurological problems
Meningitis
All below present with the symptoms of meningitis such as headache, neck pain, reduced GCS, seizures and photophobia.
Ensure airway ABV approach in all patients and if confusion/fits/ ↓GCS ensure blood sugar checked.
Acute bacterial meningitis
The symptoms and presentation are as above. Always suspect this in patients with low GCS and treat immediately if any suspicion.
Treatment is cefuroxime 2g bd with lumbar puncture to confirm diagnosis.