Monitoring Antiretroviral Therapy: The Evidence Behind the Guide

A 36-year-old woman has been on TLd, the once-daily tablet of tenofovir, lamivudine and dolutegravir, for a year. Her viral load at 6 months was suppressed. She comes for her one-year visit feeling well. Her urine dipstick shows glucose 2+ and protein 1+, yet her fasting glucose is normal. Her creatinine has crept up, and her creatinine clearance (CrCl) is now 44 mL/min. Her haemoglobin is 10.8 g/dL. She is HBsAg negative. This is an illustrative case, not a real patient.

By the end of this article you will know why she had a urine dipstick at all, what it has found, and the one drug that changes because of it.

1. Why Monitor at All?

A person on antiretroviral therapy (ART) is monitored for two different things. The first is whether the treatment is working. The second is whether a drug is doing harm. The two need different tests, and it helps to keep them apart in your head.

Is it working? The HIV viral load is the primary measure of treatment success. NACO asks for it at 6 months, at 12 months, and then once a year. The CD4 count is checked at baseline and at 6 months. Once the count is stable at 350 or above on two occasions, on suppressive ART, routine CD4 testing stops. The viral load tells you about the virus, and that is what you are treating.

Is a drug doing harm? This is where the regimen matters. Different drugs harm different organs, and the schedule follows the drug.

2. The Schedule, Drug by Drug

Here is the NACO monitoring schedule the tool carries. In the tool it is now shown as two narrower tables; here it is as one. Read the TDF and AZT columns against each other, and look at the bold entries:

The TDF column is loaded with kidney tests: the creatinine and clearance at baseline, at 3 months and then every 6 months, and a urine dipstick every 6 months for glycosuria and proteinuria. The AZT column is loaded with blood counts: a complete blood count at baseline, 4 weeks, 3 months, and then every 6 months. Every regimen gets a fasting glucose and lipids once a year, and on dolutegravir (DTG) you are watching for the metabolic syndrome. Every woman of childbearing age has a pregnancy test at each visit.

“Why does a woman with a normal blood sugar need a urine dipstick?” Because on tenofovir (TDF) the dipstick is not looking for diabetes. As the last column says, it is a screen for TDF tubular toxicity. The tubules are the part of the kidney that takes glucose back from the urine. When they are injured, glucose leaks into the urine even though the blood sugar is normal.

3. What Each Drug Does, and When

The second table in the tab is the adverse drug reaction (ADR) quick reference. In the tool it is now two narrower tables, each keeping the drug and its reaction; here it is as one:

Now put the two tables side by side. The tool does not say this in words, but the timings line up. AZT anaemia and neutropenia appear at 4 to 12 weeks, and the AZT blood count falls at 4 weeks and 3 months. TDF nephrotoxicity appears at 3 to 12 months, and the TDF creatinine falls at 3 months and then every 6 months. The schedule is set to look where the harm is expected, when it is expected. Once you see that, you will not need to memorise the schedule.

Two rows deserve a second look. Abacavir (ABC) hypersensitivity comes in the first 6 weeks, and the action is to stop immediately and never rechallenge. Nevirapine (NVP) hepatotoxicity and Stevens-Johnson syndrome (SJS) come in the first 6 to 18 weeks, and the action is again to stop immediately. These two are not reactions to watch. They are reactions to act on the same day.

4. Back to Our Patient

Glucose in the urine with a normal blood glucose, protein in the urine, and a falling clearance, on tenofovir: this is TDF tubular toxicity. The tool lists two forms of it, nephrotoxicity (a rising creatinine and a falling clearance) and Fanconi syndrome (glycosuria, phosphaturia, acidosis), and she shows signs of both. She is a year into treatment, inside the onset window of 3 to 12 months. The tool’s first instruction is plain: stop TDF immediately.

“Should we change the whole regimen, to be safe?” No. The tool changes only the offending drug. Switching the whole regimen is the answer to virological failure, which is a separate question with its own pathway, and her viral load is suppressed. Dolutegravir and lamivudine are doing their job.

So what replaces tenofovir? The tool decides on the haemoglobin. Zidovudine (AZT) can cause anaemia, so it is used only at a haemoglobin of 8 g/dL or above; below that, abacavir takes its place. Hers is 10.8, so the tool prints: AZT 300 mg twice daily with lamivudine 150 mg twice daily, alongside the same anchor drug, here dolutegravir. Because her CrCl is below 50 mL/min, it adds a warning: ask the pharmacy for the adjusted doses before the first dose is given. Lamivudine needs a reduced dose below this clearance, and so does zidovudine, and the fixed-dose combinations NACO dispenses cannot be adjusted component by component.

She moves from one tablet once a day to a twice-daily backbone, so she needs careful counselling. Her creatinine and clearance are repeated at 2 and 4 weeks, to confirm that the kidney is recovering. Her blood count is checked at 2 weeks, 4 weeks and 3 months after the switch, because she is now on zidovudine. Zidovudine is not used if the haemoglobin is below 8 g/dL.

“What if she had hepatitis B?” Then stopping tenofovir would remove her hepatitis B cover, and the tool warns of a severe hepatic flare. It suggests tenofovir alafenamide (TAF) 25 mg, which is kinder to the kidney, or adding entecavir 0.5 mg once daily, with liver tests weekly for 4 weeks. This is why the tool asks for the hepatitis B status before it gives an answer.

5. The Common Mistake

The common mistake is to read a monitoring test without asking which drug it is watching. It is easy to see why: the tests are routine, the reports come back in a pile, and a dipstick with glucose looks like a diabetes problem. But in a person on tenofovir, glycosuria with a normal blood sugar is the kidney speaking. Read every test against the regimen, and against the column it came from.

Try This

A man started AZT, lamivudine and dolutegravir 8 weeks ago. His haemoglobin has fallen from 11.5 to 7.6 g/dL. His CrCl is 72 mL/min, and he is HBsAg negative. What is happening, and what changes? Illustrative case.

Answer. Anaemia at 8 weeks on zidovudine sits in its onset window of 4 to 12 weeks. The tool’s action is to switch AZT to TDF or ABC. His CrCl is 50 mL/min or above, so tenofovir is allowed, and with dolutegravir as the anchor he moves to the TLd fixed-dose combination, one tablet once daily. Look for other causes of the anaemia too: iron deficiency, folate, chronic disease. Consider a transfusion if the haemoglobin is below 7 with symptoms, and repeat the blood count at 2 and 4 weeks.

Take-Home Points

• The viral load tells you whether ART is working: 6 months, 12 months, then once a year.
• The schedule follows the drug: kidney tests and a urine dipstick for tenofovir, blood counts for zidovudine.
• The timings follow the times to onset: AZT counts at 4 weeks and 3 months, TDF creatinine at 3 months and then 6-monthly.
• Glycosuria with a normal blood glucose on tenofovir is tubular toxicity: stop TDF, and change only that drug.
• Abacavir hypersensitivity and nevirapine hepatotoxicity or SJS: stop immediately; never rechallenge abacavir.

For the first regimen and the switch to second line, use the CDSS tools: First-Line ART Selection and Second-Line ART Pathway.

Declaration: the author built and maintains the tool. It is free to use. The figures in this article are those the tool carried on 5 November 2026, in its Monitoring tab and in the substitution it prints, each from the NACO and WHO guidance the tool names. The illustrative cases follow the tool’s rules; check the tool’s result for a real patient.

References

1. NACO. National Guidelines for HIV Care and Treatment. MoHFW, GoI; 2021.
2. NACO. National Technical Guidelines on ART. 2018 (Updated 2021).
3. WHO. Consolidated guidelines on HIV. 2021.
4. World Health Organization. WHO updated recommendations on HIV clinical management: recommendations for a public health approach. Geneva: WHO; 7 January 2026.