HIV Treatment Explained: Antiretrovirals and the First-Line TLD Pill

On the day someone learns they have HIV, their first question is usually not about medicine. It is "What happens to my life now?" I want to say from the start that today's HIV medicine is very different from 20 years ago. Most people take just one tablet a day, side effects are few, and if you take it consistently you can live, work, love and have a family as normal. This article introduces antiretroviral medicine, especially the TLD regimen used as first-line treatment in Thailand.

How does antiretroviral therapy (ART) work?

Antiretroviral therapy (ART) is medicine that stops HIV from multiplying in the body. Each drug class acts at a different point in the virus's life cycle, for example:

• Nucleoside reverse transcriptase inhibitors (NRTIs), such as tenofovir, lamivudine and emtricitabine, stop the virus copying its genetic material.
• Integrase inhibitors (INSTIs), such as dolutegravir, stop the virus inserting itself into the genetic material of our cells.
• Other classes, such as NNRTIs and protease inhibitors, are used in some situations, for example drug allergy, drug resistance or interactions with other medicines.

Because several drugs are used together, it is hard for the virus to become resistant. The goals of treatment are:

1. To suppress the amount of virus in the blood (viral load) until it is undetectable
2. To let the CD4 count recover and prevent opportunistic infections
3. To stop sexual transmission to partners, according to U=U
4. To have a quality of life and lifespan close to everyone else's

The medicine does not remove all the virus hiding in cells, so it must be taken for life. If you stop, the virus starts multiplying again within a few weeks.

When should treatment start?

The World Health Organization (WHO) and Thailand's national HIV guidelines recommend starting treatment for everyone diagnosed with HIV, whatever their CD4 count, and starting early, within 7 days of diagnosis, or even on the same day (same-day ART) if the person is ready. Studies in Thailand under the universal health coverage system found that starting treatment early was linked to better outcomes.

The important exception is suspected cryptococcal (fungal) meningitis or tuberculous meningitis. In these cases the doctor treats the infection first for a while, then starts antiretrovirals, to reduce severe inflammation as the immune system recovers (immune reconstitution inflammatory syndrome, IRIS). Read more in CD4 and opportunistic infections.

What is TLD, and why is it the first-line regimen?

TLD is three drugs combined in one tablet:

• T = tenofovir disoproxil fumarate (TDF) 300 mg
• L = lamivudine (3TC) 300 mg
• D = dolutegravir (DTG) 50 mg

The WHO has recommended dolutegravir-based regimens as first-line treatment for adults and adolescents since 2019, including women of reproductive age and pregnant women, after follow-up data showed that the concern about neural tube defects in babies was very low. Thailand's guidelines also use TLD as the main regimen. Its advantages are:

• One tablet a day at the same time, with or without food
• It suppresses the virus quickly; most people are undetectable within 3–6 months
• The virus becomes resistant less easily than with older efavirenz-based regimens
• Fewer neuropsychiatric side effects than older regimens

For some people, the doctor may choose a different regimen, for example tenofovir alafenamide (TAF) instead of TDF when there are kidney or bone problems, or another regimen because of interactions with other medicines. Long-acting injectable treatment (cabotegravir with rilpivirine) is used in many countries, but it is still an option for specific groups. The choice of regimen must be assessed by a doctor for each person.

TLD, 1 pill daily

T = Tenofovir (TDF)

NRTI class

• Stops the virus copying its genes
• Also treats hepatitis B

L = Lamivudine (3TC)

NRTI class

• Stops the virus copying its genes
• Works together with tenofovir

D = Dolutegravir (DTG)

INSTI class

• Stops the virus inserting into cell DNA
• Harder for resistance to develop than older drugs

WHO has recommended dolutegravir-based first-line regimens since 2019. The regimen is chosen as assessed by your doctor.

How to take TLD well, and medicines to watch out for

• Take one tablet a day at the same time every day. A phone alarm helps a lot.
• If you forget, take it as soon as you remember. But if it is nearly time for the next dose, skip the missed one and take the next dose as usual. Never take two tablets at once.
• Antacids containing aluminium or magnesium, calcium, iron, zinc and multivitamins with minerals reduce the absorption of dolutegravir. Take TLD at least 2 hours before or 6 hours after them (for calcium or iron, taking them together with a meal is another option if your doctor advises). Read Calcium, zinc and vitamin D before buying supplements on your own.
• The tuberculosis medicine rifampicin lowers dolutegravir levels, so the doctor must adjust the dose.
• The diabetes medicine metformin may reach higher levels, so the doctor must adjust the dose.
• Always tell your doctor about herbal medicines, supplements and other medicines you use, including gender-affirming hormones, which can generally be used with TLD but should be under a doctor's care.

Possible side effects

In the first 2–4 weeks, some people have nausea, diarrhoea, headache, trouble sleeping or vivid dreams. Most of these improve on their own. If you cannot sleep, taking the medicine in the morning may help. Talk to your doctor before changing the time.

Long-term things to monitor

• Kidney function and bone density, because of TDF
• Weight gain, which can occur with dolutegravir-based regimens, so it is worth looking after your diet and exercise from the start
• Creatinine may rise slightly because of dolutegravir without meaning kidney damage. Your doctor will interpret this for you

See a doctor promptly if you have a severe rash, fever, yellow eyes or skin, severe abdominal pain, or low mood with thoughts of harming yourself (you can call 1323, Thailand's free 24-hour mental-health hotline; Thai language, ask for English support).

Tests before and during treatment

Before starting, the doctor usually checks:

• Confirmation of the HIV result and the CD4 count
• Kidney function (creatinine), liver function, blood sugar and lipids
• Hepatitis B (HBsAg) and C, syphilis and other sexually transmitted infections according to risk
• Tuberculosis screening, and cryptococcal antigen (CrAg) testing if the CD4 count is low
• A pregnancy test for anyone who could be pregnant
• In some cases, a drug resistance test before starting

But you do not need to wait for every result before starting treatment. For follow-up, viral load is usually checked about 6 months after starting, and then at least once a year once it is well controlled. If the viral load is above 1,000 copies/mL, the doctor will review how the medicine is being taken and consider a drug resistance test.

1. Diagnosis day
   Baseline tests, can start now

   CD4, kidney, liver, hepatitis B, syphilis; no need to wait for all results

2. ≤ 7 days
   Everyone starts

   Regardless of CD4; same-day start if ready

3. 2–4 weeks
   Early side effects ease

   Nausea, headache, poor sleep usually pass

4. ~6 months
   Viral load test

   Most are undetectable within 3–6 months

5. Every year
   Viral load at least yearly

   Above 1,000 copies/mL: doctor reviews adherence and resistance

Per WHO and Thai guidance, except when fungal meningitis or TB is suspected, where that infection is treated first.

Treatment coverage and care at Dr. Kris Clinic

Thai nationals receive antiretroviral medicine and follow-up tests free of charge through the Universal Coverage (gold card) scheme, Social Security or the civil servant scheme, at their registered hospital. Foreign residents and visitors usually receive care at private hospitals or clinics, or through their insurance. Treatment information is confidential by law.

At Dr. Kris Clinic in Surat Thani, I help from counseling after a diagnosis, explaining medicines and side effects in plain language and planning tests before treatment, to caring for sexual health issues that come with HIV and helping coordinate entry into the right treatment system. Online consultations are available nationwide, and English-speaking consultations are available. If you have just received your result, read Living with HIV and The 10 most common HIV questions, then come and talk with me.