A Quick Approach to HIV Treatment (Adults)

Topics / Medical / HIV and related conditions

Summary This is a brief article discussing an approach to the management of HIV. It discusses how we should start treatment, when can we defer the patient's treatment, what are the baseline assessments, baseline investigations and how to manage a newly diagnosed HIV positive patient.

How to start treatment

All patients that have been newly tested as HIV positive should be initiated on ART within 7 days unless there is a reason to defer the patient’s treatment. If possible, the patient should be initiated on ART on the same day. This is called, “test and treat”. If the patient IS ALREADY ON ART and develops any of the conditions stated under, “reasons to defer ARTs, ” one should NOT interrupt their ART treatment.

Reasons to defer ARTs

TB Symptoms (cough, night sweats, fever, recent weight loss)
1. If the patient doesn’t have TB: Initiate ART the same day or within 7 days
2. If the patient has confirmed Drug Sensitive-TB, at a non-neurological site:
  1. If CD4 < 50, then start ART within 2 weeks of starting TB treatment
  2. If CD4 > 50, then start ART after 8 weeks of starting TB treatment. This means you would wait to finish the Intensive Phase.
3. If the patient has confirmed Drug Sensitive-TB, at a neurological site: Strat ART treatment after 2 weeks + Once symptoms improve + if the TB treatment is tolerated.
Meningitis symptoms (headache, confusion, fever, neck stiffness or coma)
1. You need to investigate for meningitis before starting ART
  1. If the patient has TBM: Start treatment 4-8 weeks after starting TB treatment
  2. If the patient has Cryptococcal Meningitis: Start 4-6 weeks after starting antifungal treatment
CrAg-positive, but no Meningitis symptoms/signs: Start ART 2 weeks after starting fluconazole treatment
Other acute illnesses such as PJP or bacterial Pneumonia: Start treatment 1-2 weeks after starting treatment for that infection (PJP/Pneumonia)
Clinical Symptoms/Signs of liver disease: You need to test the patient’s LFT by checking ALT and bilirubin. If ALT > 120 IU/L with symptoms of hepatitis such as nausea, vomiting, right upper pain AND/OR Bilirubin > 40umol/L – Then you should try and investigate this before starting the ARTs.

Baseline Clinical Assessments

Danger signs needing urgent care – use Adult Primary Care guidelines, Maternity Care Guidelines, or the IMCI Chart booklet to treat
Nutritional assessment – use BMI, MUAC < 23 for pregnant women, and the z-scores for children to identify patients who require nutritional assistance and lifestyle support.
TB Screen – if no TB symptoms (cough, night sweats, fever, weight loss), consider TB Preventative Therapy. In pregnant women, you need to also do a GeneXpert regardless of symptoms.
Meningitis screen (headache, confusion, visual disturbances, fever, neck stiffness, coma)
Mental health/Substance use screen – Efavirenz and to a lesser extent Dolutegravir may be associated with neuropsychiatric side effects (Screen for psychosis, depression, substance abuse) and we also know that substance use may affect the patient’s adherence to their medications.
Chronic Non-Communicable Disease Screen such as Diabetes Mellitus, Hypertension, Epilepsy
Pregnancy Screen, if not pregnant consider family planning. If pregnant, assist with a referral for antenatal care and PMTCT
STI screen (any discharge, ulcers? Or recent treatment for STI in the past 8 weeks)
HIV Staging is very important because it helps with assessing severity, the timing of ART initiation, and the need for cotrimoxazole prophylaxis (CPT).

Baseline Investigations

Confirm HIV status
CD4 count: Helps identify patients who will benefit from Co-trimoxazole Preventative Therapy (CPT), CrAg screening, and patient’s immunological status. Note how viral load is NOT needed as a baseline investigation.
1. If CD4 < 200 or WHO Stage 2,3 or 4: Start CPT
2. If CD4 < 100, the laboratory will perform a reflex CrAg test. If it is NEGATIVE then there is no need for fluconazole therapy. However, if CrAg is positive, then these patients will benefit from a lumbar puncture and treatment for their infection. You should defer ART for these patients as stated above.
Renal Function: Creatinine and eGFR is required to detect renal insufficiency and of course, eligibility for TDF. Tenofovir is nephrotoxic. Non-pregnant individuals should have an eGFR > 50 and Pregnant individuals should have an absolute creatinine level < 85 umol/L in order to be eligible for TDF.
Hematology: Hemoglobin should be tested in order to rule out anemia. If the Hb is < 10 then a formal anemia workup should be done. If the Hb is < 8 then AZT should be avoided since it also causes anemia. In pregnant women, a Hb < 10 should prompt the doctor to initiate iron supplementation. However, a reason for referral would be if the anemia is < 8 or the woman is ≥ 36 weeks of pregnancy. Always remember that iron supplementation and Dolutegravir have interactions.
TB Screen – GeneXpert: This will be used to screen for patients for TB, however, it is only done in patients which have symptoms of TB. The guidelines state that for pregnant women this should be done routinely regardless of the symptoms.
Hepatitis Screen – HBsAg: It is important to screen the patients for Hepatitis B co-infection. This is because if the patient is Hepatitis B co-infected then a Tenofovir (TDF) containing regime is preferred. It is also worth noting that if they are Hepatitis B co-infected then they have a risk of developing hepatitis flares once Tenofovir is stopped.
Cervical Cancer Screening: The guidelines state that patients should be screened at baseline and then every 3 years. If positive, then one should refer the patient accordingly. However, it is worth noting that it is probably more cautious if HIV-positive patients receive yearly pap smears if possible.

Treatment

1. Regimes

Adults, including pregnant women, and adolescents ≥ 35kg and ≥ 10 years of age should be started on TLD (Tenofovir 300mg, Lamivudine 300mg, Dolutegravir 50mg)
Patients who are already receiving treatment for Drug Sensitive-TB should be initiated using TEE (Tenofovir 300mg, Emtricitabine 200mg, Efavirenz 600mg), ideally taken at night. This choice is because of the drug-drug interaction of Dolutegravir with TB treatment.
If the patient is < 35 kg and/or < 10 years then you should focus on the pediatrics guidelines for HIV treatment since Tenofovir cannot be used for them. Dolutegravir may be used up until 20kgs.
NB: One should be aware that TLD is the new regime and TEE is the older regime. Dolutegravir is a very good drug that has the following benefits (1) rapid viral suppression (2) high genetic barrier to resistance (3) no interactions with hormonal contraceptives (4) mild/uncommon side effects. Common side effects include (1) insomnia (2) headaches (3) GIT disturbances. Dolutegravir has a small risk of Neural Tube Defects if taken around conception or during the first 6 weeks of pregnancy while the neural tube is still developing. This concern was raised in a study done in Botswana in 2018. However, in folate-fortified countries like South Africa, this risk showed to be much lower than expected. In South Africa, everyone should be ideally started on TLD except women who currently want to conceive OR in women who are starting ART for the first time in the first 6 weeks of pregnancy. Dolutegravir also has some important drug-drug interactions with TB treatment, Diabetic Treatment, Epileptic treatment, Calcium/Iron supplements, and some antacids. It can be taken in the morning or in the evening.
Patients who are TB positive, and receiving Rifampicin should have the dose of Dolutegravir increased to 50mg 12 hourly. For instance, if the patient has a fix-dosed combination (FDC) of TLD (300,300,50) then Dolutegravir 50mg PO should be added 12 hours after the FDC. This should be continued for 2 weeks after stopping the Rifampicin. Rifampicin also has an effect on Protease Inhibitors such as LPV/r and one should become more informed about drug-to-drug interactions.
Patients who are Diabetic on Metformin can only receive a maximum dose of Metformin 500mg PO 12 hourly since Dolutegravir causes an increase in the levels of Metformin.
TLD is the first line of treatment for HIV, this means that we should aim to switch patients from TEE to TLD. This should only be done if the patient is virologically suppressed (<50 copies/ml) in the last 6 months to avoid changing “one drug” in a regimen that is failing otherwise this would result in increased drug resistance.
Drug classes: Tenofovir (NRTI), Lamivudine (NRTI), Dolutegravir (Integrase Inhibitor), Emtricitabine (NRTI), Efavirenz (NNRTI).

2. Opportunistic infections (OIs) and associated conditions

If the patient is newly diagnosed HIV positive and has a condition under “Reasons to defer ARTs, ” then one should consider delaying ARTs. Otherwise, any opportunistic infection and associated condition should be treated. For instance, common opportunistic infections and associated conditions include dermatological conditions, oral/oropharyngeal candidiasis, and chest infections such as pneumonia, TB, or PJP. Neurological (such as meningitis) and other common malignancies such as Kaposi sarcoma and cervical carcinoma.

3. CPT and TPT Preventative Therapies

Consider the need for Preventative Therapies: Co-trimoxazole Preventative Therapy (CPT) and TB Preventive Therapy (TPT).

Follow up

Clinical Screen:
1. Anthropometry screen
2. TB Screen
3. Pregnancy Screen, family planning
4. Side effects and compliance screen
5. WHO clinical staging
Laboratory Screen:
1. Virological and Immunological Monitoring:
  1. CD4 count: Should be done at baseline AND after 1 year of ART. The CD4 count should only be repeated earlier than that (6 monthly) if the CD4 is < 200 or the viral load is ≥ 1000. You can stop monitoring the CD4 6 monthly once the viral load becomes < 1000 or the CD4 becomes > 200.
  2. Viral load (HIV RNA): Should NOT be done at baseline, since one would expect the viral load to be elevated either way. Once the patient is started on treatment one would expect a 1-log decrease/month (10-fold decrease per month). Hence, in 6 months we would likely expect the patient to become virologically suppressed. It should be repeated at month 6, at month 12 then yearly if the patient is virologically suppressed. A viral load < 50 is said to be “suppressed”, while a viral load ≥ 1000 is said to be “unsuppressed”. A viral load between 51 – 999 is in a transition period. Read more about viral load and the different actions that one needs to take during the monitoring period.
2. Tests to do depending on the drug that the patient is currently taking:
  1. Tenofovir (TDF): One needs to monitor Creatinine at months 3, 6, and 12 then 12-monthly after that. This is because Tenofovir is nephrotoxic. One of the many reasons a patient with HIV may develop renal impairment.
  2. Zidovudine (AZT): Full blood count and differential should be done at month 3, month 6, and then only if it is clinically indicated. If the Hb is greater than 8 g/dL then one can continue with AZT, but if it drops below 8 then one should aim to use an alternative agent. This is because AZT can cause anemia.
  3. Protease Inhibitors (LPV/r, ATV/r): Cholesterol and Triglycerides should be tested at month 3. If it is abnormal/above the reference ranges then you should do fasting cholesterol and triglycerides. This is because Protease Inhibitors have metabolic side effects.
  4. Nevirapine, Efavirenz, or TB treatment: Request ALT if the patient has signs/symptoms of hepatitis such as nausea, vomiting, and yellow discoloration (jaundice).

References and Further Reading 1. 2019 ART Clinical Guidelines - March 2020 updates
2. Medicines Information Cenre, UCT: NDOH ART Adult Poster 2019

Published on 17 August 2022

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