A look at the benefits of antiretroviral therapy and recommendations
Positively Aware Christopher M. Nguyen, PharmD, AAHIVP
Christopher M. Nguyen, PharmD, AAHIVP

Without HIV medications, known as antiretroviral therapy (ART), most people living with HIV will go on to develop severe depletion of their CD4 (T-cells), leading to AIDS-related illnesses and premature death. The recommendations on when to start someone on ART and what to treat with has changed over the years due to both availability of strong evidence and potent drug options with minimal side effects.

The Department of Health and Human Services (DHHS) makes guidelines and recommendations on when to treat and what to treat with. Historically, individuals newly diagnosed with HIV present to care already with low CD4 count, and we started ART based on his or her CD4 level.

However, we know that durable viral suppression (being undetectable) using ART improves immune function, reduces the risk for complications and illnesses, and prolongs life. Furthermore, starting someone on ART early while their CD4 is still high better preserves the immune system and allows for more robust CD4 recovery. How well your CD4 bounces back is directly related to your CD4 level when ART is started. That is to say, the higher your CD4 is at the start of treatment, the better CD4 preservation and improvement you will see. Many people who start ART when their CD4 is too low do not see significant CD4 improvements at all, even years after they’ve been on treatment. For these reasons, individuals vulnerable to HIV infection should get tested regularly and be connected to care as soon as possible if a positive diagnosis is made.

TREATMENT FOR ALL

The DHHS panel has recommended starting ART in all individuals, regardless of CD4 count at diagnosis, since 2012. However, the strength of the recommendation differed based on a person’s CD4 level because at that time, we didn’t have enough evidence to make a strong recommendation to start ART in people with CD4 above 500 cells/mm3.

Recently, results from two large randomized controlled trials (the strongest type of study) definitively demonstrate the benefits of starting ART in those with high CD4 count.

The START and TEMPRANO studies randomized HIV-positive participants to two groups: one group received ART immediately when their CD4 count was still high (more than 500 cells/mm3), and ART was delayed in the second group until their CD4 level dropped. In both studies, there was about a 50% reduction in morbidity and mortality (AIDS and non-AIDS related illnesses or serious events, and death) among individuals who received ART immediately versus those who deferred treatment. The results from these studies allowed the panel to make strong recommendations to start ART in all individuals with HIV regardless of CD4 count.

REDUCING TRANSMISSION

Beyond the benefits to the individual living with HIV, viral suppression using ART significantly reduces the risk of transmission to HIV-negative partners.

The HPTN 052 study of serodiscordant couples (when one partner is HIV-negative and the other HIV-positive) showed a 96% reduction in risk of HIV transmission when the HIV-positive partner is on treatment. Most of the couples in the study were heterosexual.

In the PARTNER study, which included a good number of MSM serodiscordant couples, investigators found no cases of transmission. However, it does not mean that transmission cannot occur, especially for the most risky act (condomless receptive anal intercourse with ejaculation); but the investigators concluded that the risk is very low.

The PARTNER 2 study is underway which will hopefully give more precise estimates of transmission risk in the MSM population. Even though the results of these studies are dramatic, safer sex methods should be practiced, and additional information regarding HIV transmission can be found at aidsinfo.nih.gov.

STARTING THERAPY

The decision to initiate ART should be a conversation between you and your provider, taking into account the known benefits of starting early. The DHHS panel noted that the decision should always include consideration of an individual’s other medical conditions and his or her willingness and readiness to initiate therapy. The success of ART is highly dependent on adherence to therapy. 

The newer regimens, those recommended by the panel, are well tolerated in general. However, each person may react differently to the same medicine, and some side effects are more common than others. While taking medications, discuss any physical changes or new symptoms with your doctor and pharmacist. Some side effects can be managed or controlled, while others require intervention or medication changes. Some side effects are rare.

One potential reaction when someone starts ART is known as immune reconstitution inflammatory syndrome (IRIS), which may occur as the immune system regains strength and viral load drops following initiation of therapy. 

Low CD4 at the start of treatment is a risk factor for IRIS, another reason why you should start early. Symptoms of illnesses such as shingles and tuberculosis should be reported to a health care provider immediately. See drug page or package insert for more information.