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HMR 1st Qtr 2013: Frequently-asked questions to the National HIV & TB Health Care Worker Hotli
 

HMR Africa

*Annoesjka Swart

Why does my patient’s CD4 count not rise even though he is on antiretrovirals and virologically suppressed?

In most adherent patients who start antiretroviral therapy (ART), the viral load will be below the limit of detection by six months. In addition, the CD4 count will rise in a biphasic manner. On average, the CD4 count will rise around 75 cells/µl in the first month, followed by a more gradual rise thereafter of around 80 cells/ µl per year.




However, CD4 responses are highly variable. Ten to twenty percent of patients who achieve and sustain virological suppression will experience no rise in CD4 count, or a very delayed or suboptimal rise in CD4 count. This phenomenon has been termed “immunologic discordance”.

“Immunologic discordance” may be caused by several factors including damage to the thymus from chronic HIV infection, and immune activation on ART resulting in CD4 T-cell death. It seems to be more common in patients who start ART at an older age.

Patients with immunologic discordance have a better prognosis compared to untreated patients with the same CD4 count, but their risk for mortality or AIDS progression is two to three-fold higher than patients who have an adequate CD4 response to ART. If these patients are clinically unwell, it is also important to consider an opportunistic infection (especially TB) or lymphoma that may cause a low CD4 count.

Changing ART in patients with immunologic discordance does not improve the CD4 count. Therefore we do not recommend switching or intensifying ART because there is no evidence of benefit. We advise continuing the current ART regimen and cotrimoxazole prophylaxis if the CD4 count remains more than 200.

Reference: Aid for AIDS Healthcare Professional Newsletter, February 2012 – Issue 31.

If my patient is on nevirapine and needs to start TB treatment with rifampicin, must I change the nevirapine to efavirenz?

Both efavirenz and nevirapine interact with rifampicin, resulting in lower levels of the ARV, but the interaction with efavirenz is a lot less clinically significant. Therefore, efavirenz is the preferred NNRTI for use with rifampicin. NVP is an alternative in patients with contra-indications for EFV (e.g. psychosis), but it carries a higher risk of hepatitis and virological failure when used with rifampicin.

We recommend that patients who start TB treatment with rifampicin be changed from nevirapine to efavirenz unless efavirenz is contra-indicated.

Reference: Meintjies G et al. Guidelines for antiretroviral therapy in adults by the Southern African HIV Clinicians Society. Southern African Journal of HIV Medicine. September 2012; 13 (3): 114-133.

How should I deal with a nevirapine (NVP) or efavirenz (EFV)- induced rash?

Rash with NNRTIs is common in the first six weeks of therapy and is usually more severe and frequent with NVP. If the rash is accompanied by systemic features such as a fever, elevated ALT or hepatitis, mucosal involvement or blistering, the NNRTI should be discontinued immediately. Rechallenge with the same drug must not be performed.

If the rash is mild and occurs without systemic features, blistering or mucosal involvement, the NNRTI can be continued and the rash can be treated with antihistamines and, possibly, topical steroids. Systemic steroids should not be used.

In patients who develop rashes during the low dose NVP “lead-in” phase (200 mg daily), the dosage must not be increased to 200mg 12 hourly until the reaction has completely resolved. This “treat-through” approach is only acceptable if the patient can be carefully observed, otherwise NVP should be substituted.

It is acceptable to substitute EFV for NVP in the event of hypersensitivity, unless the reaction was severe. Substituting NVP for EFV is not recommended.

Reference: Meintjies G et al. Guidelines for antiretroviral therapy in adults by the Southern African HIV Clinicians Society. Southern African Journal of HIV Medicine. September 2012; 13 (3): 114-133.

How should I deal with a viral load of > 50 copies/ml?

Viral load monitoring is very important to the success of antiretroviral therapy (ART). If the viral load is undetectable, then the virus cannot mutate and develop resistance. In the public sector viral loads are done four to six months after initiating ART, and then annually thereafter.

A viral load >50 copies/ml while a patient is receiving ART should be an indication for urgent action to improve adherence. The viral load should be repeated three months after adherence support is stepped up and an ART change must be considered if there is not complete viral suppression at the three month follow-up viral load.

Treatment success is defined by a decline in viral load to <50 copies/ml within six months of commencing ART and sustained thereafter.

Treatment failure is defined by a confirmed HIV viral load of >1000 copies/ml in two measurements taken one to three months apart. Inadequate patient adherence remains the most common cause for treatment failure. Other reasons include: prior use of single-dose nevirapine for PMTCT, especially when ART is initiated within six months of the PMTCT dose; drug interactions that decrease the levels of ARVs; and transmitted resistance, which is currently uncommon in South Africa (<5%).

What to do in patients who have persistently detectable viral loads at low levels (200 – 1000 copies/ml)?

If patients have low level viraemia (slightly raised viral load) for longer than a year, or persistently low CD4 counts (<100 cells/µl) together with low-level viraemia despite adherence interventions, they should be switched to second-line ART.

What do I restart my patient on who has defaulted?

In general we recommend restarting the same regimen that the patient was on before defaulting, provided that they were not failing the regimen. A viral load should be done at three months. If the viral load is not suppressed at three months, switching to a second-line regimen should be considered.

If the patient was on d4T during first-line therapy, this can be substituted with AZT, but not TDF, because, if the patient already has pre-existing NNRTI and 3TC resistance, TDF resistance may rapidly develop, which may compromise second-line options.

Is it necessary to double the dose of aluvia (lopinavir + ritonavir) in all patients on TB treatment?

No, only patients who are taking rifampicin-containing TB treatment and lopinavir + ritonavir concurrently need to double the dose of lopinavir + ritonavir. This should be done slowly over two weeks. Monitoring of liver function (ALT) is recommended while patients are on this double dose. Also remember to decrease the dose back to the normal dose two weeks after patients have completed their TB treatment with rifampicin.

How do I manage the haematological toxicity of zidovudine (AZT)?

Full blood count (FBC) and/or haemoglobin (Hb) monitoring is needed with AZT. This is done at baseline, and at month 1, 2, 3 and 6. AZT may cause anaemia and neutropaenia. Platelet counts do not drop with AZT; if your patient has thrombocytopaenia, he/she needs to be referred to a doctor for further investigation.

Reference: Meintjes G et al. Guidelines for antiretroviral therapy in adults by the Southern African HIV Clinicians Society. SAJHIVMED Sept 2012;13(3): 114 – 131.

*Annoesjka Swart, Medicine Information Pharmacist. BSc Pharm, Univ. Stellenbosch. Manager, Medicines Information Centre, Clinical Pharmacology, UCT.

More about the National HIV & TB Health Care Worker Hotline:

Since March 2008, the Medicines Information Centre, in collaboration with the Foundation for Professional Development and PEPFAR/USAID, has operated the National HIV & TB Healthcare Worker Hotline. The offices for the toll-free hotline are situated in the Division of Clinical Pharmacology at the University of Cape Town, where free information is provided to all healthcare workers in South Africa on HIV- and-TB patient treatment.

The queries are handled by four specially-trained drug information pharmacists who share more than 50 years of drug information experience between them. They have direct access to the latest information databases and reference sources, as well as to a network of experienced clinicians and consultants across South Africa.

 

Posted on Monday, May 27 @ 11:41:17 SAST by E-Doc
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