Dosing frequency and number of pills don't affect HIV treatment outcomes

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Levels of adherence to modern HIV treatment are unaffected by dosing frequency or number of daily pills, Italian investigators report in HIV Medicine. However, people who were taking larger numbers of pills reported poorer health. The investigators suggest this is because “many of the patients receiving more complex regimens had more advanced disease and/or were harbouring virus with more drug-resistance mutations.”

It has been uncertain if frequency of dosing and daily pill burden affect adherence to antiretroviral therapy. Research conducted soon after combination HIV treatment was first introduced showed that adherence and outcomes were poorer in people taking more complicated regimens with larger numbers of pills.

However, there have been significant advances in HIV therapy in recent years, with treatment becoming simpler, more potent and less toxic.


pill burden

The number of tablets, capsules, or other dosage forms that a person takes on a regular basis. A high pill burden can make it difficult to adhere to an HIV treatment regimen.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.


A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

Italian investigators wanted to gain a better understanding of the relationship between the number of daily doses and pills and HIV treatment outcomes in the era of modern antiretroviral therapy.

They therefore designed a study involving 2114 people who received HIV care in Milan between March and May 2010. Adherence and self-reported health status were assessed using questionnaires.

The study participants had a median age of 46 years and 78% were men. The median duration of antiretroviral therapy was ten years. Median CD4 cell count was 598 cells/mm3 and 85% of participants had an undetectable viral load. Most (57%) were taking a once-daily antiretroviral regimen. The remaining 43% were taking their treatment twice daily. The median number of daily pills taken by each participant was 3.67. The most commonly used combinations of drugs were efavirenz/tenofovir/FTC (Atripla) (14%); ritonavir-boosted atazanavir (Reyataz) with tenofovir/FTC (Truvada) (12%); and lopinavir/ritonavir (Kaletra) with tenofovir/FTC (7%).

Over three-quarters (79%) of study participants reported taking all their doses.

Adherence levels did not differ according to whether treatment was taken once- or twice-daily. People taking once- and twice-daily therapy were equally likely to have missed at least one dose of their medication in the previous week (17% vs 16%) and to have stopped treatment for two or more days in the previous month (11% vs 10%).

People with an undetectable viral load reported better adherence than those with a detectable viral load (95% vs 88%, p < 0.002). Higher levels of adherence were also associated with better self-rated health status (p < 0.001).

“We observed a direct correlation between self-reported health status and adherence, which suggests that patients experiencing more drug side effects not only experience worse health, but are also more likely to miss doses”, comment the investigators.

CD4 cell counts were highest in people who had the best adherence (p < 0.001).

Taking a greater number of pills each day was associated with poorer self-rated health status (p = 0.019). However, there was no evidence of a relationship between frequency of dosing and health status.

“Better self-reported health status was associated with a lower pill burden,” write the authors. “Neither the number of daily pills not dosing interval was associated with self-reported adherence.”

They believe their findings show that “when a regimen is well tolerated, adherence and health status are very good, regardless of the number of daily pills or the dosing schedule.”

The investigators stress that their study participants were “highly adherent and virologically suppressed” and conclude “self reported adherence was not associated with the number of daily pills or dosing interval.” They believe their findings “may be clinically important when, because of toxicity, a patient is a candidate for a switch from a very simple nucleoside reverse transcriptase inhibitor (NRTI)-based regimen to a more complex NRTI-sparing regimen.”


Gianotti N et al. Number of daily pills, dosing schedule, self-reported adherence and health status in 2010: a large cross-sectional study of HIV-infected patients on antiretroviral therapy. HIV Med, online edition. DOI: 10.111/j.1468-1293.2012.01046.x, 2012.