When should you start HIV medication?

When should you start HIV medication?

In nearly all cases, people should start treatment with antiviral drugs as soon as they are diagnosed with HIV.
In nearly all cases, people should start treatment with antiviral drugs as soon as they are diagnosed with HIV.

In general, medical professionals now believe the best chance for an HIV (human immunodeficiency virus) patient to protect and maintain their immune system health is to start aggressive treatment upon diagnosis in almost all cases. In the past, doctors thought that waiting until disease markers on blood tests reached a certain level could be better for the patient’s chances of survival and quality of life. Despite the potential danger of viral resistance and long-term drug side effects, studies have subsequently shown that starting antiviral medication early is the best option for nearly all people with HIV.

After 40 years of researching HIV/AIDS, clinicians, drug researchers, epidemiologists, and public health professionals have succeeded in making the virus much less deadly. Part of this effort included developing treatment guidelines about when, how, and under what conditions to initiate antiviral therapy to control the HIV infections.

AIDS (acquired immunodeficiency syndrome) is the end result of unchecked HIV infection. In other words, not all people with HIV have AIDS, but everyone with AIDS has HIV. “AIDS” describes the immune system collapse that opens the door for opportunistic infections and cancers. Without successful intervention, these secondary conditions typically kill the patient.

Most people with HIV infection can now live long and relatively healthy lives, as long as they stick to the antiviral drug cocktail prescribed by their treatment team. In most cases, the current treatments started at the right time can prevent the virus from causing full-blown AIDS.

How do doctors treat HIV infections?

First, there is no evidence that people infected with HIV can be cured by the currently available therapies, although research related to curing people of infection is underway. In general, those who are treated for years and are repeatedly found to have no virus in their blood by standard viral load assays will experience a prompt rebound in the number of viral particles when therapy is discontinued. Consequently, the decision to start antiretroviral therapy (ART) must balance the risk versus the benefits of treatment. The risks of therapy include the short- and long-term side effects of the drugs, as well as the possibility that the virus will become resistant to the therapy, which can limit options for future treatment. The risks of both of these problems are quite small with the treatment options currently available.

A major reason that a person’s infection develops resistance to a particular drug regimen is the patient's failure to correctly follow the prescribed treatment, for example, by not taking the medications at the correct time. If virus remains detectable by blood test on any given regimen, resistance eventually will develop. Indeed, with certain drugs, resistance may develop in a matter of weeks, such as with the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine (Epivir, 3TC) and emtricitabine (Emtriva, FTC), the drugs in the class of nonnucleoside analogue reverse transcriptase inhibitors (NNRTI) such as nevirapine (Viramune, NVP), delavirdine (Rescriptor, DLV), efavirenz (Sustiva, EFV), and rilpivirine (Edurant, RPV), as well as the integrase strand transfer inhibitors (InSTIs) such as raltegravir (Isentress, RAL) and elvitegravir (Vitekta, EVG).

Thus, if these drugs are used as part of a combination of agents that do not suppress the viral load to undetectable levels, resistance will develop rapidly and the treatment will lose its effectiveness.

In contrast, HIV becomes resistant to other drugs, such as the boosted protease inhibitors (PIs), over months. Resistance also seems to be relatively uncommon with some of the newer InSTIs, such as dolutegravir (Tivicay, DTG) and bictegravir (BIC), which is only available as a combination pill (Biktarvy) with tenofovir alafenamide (TAF) and emtricitabine (FTC). It is important to note that when resistance develops to one drug, it often results in resistance to other related drugs, so-called cross-resistance. Nevertheless, HIV-infected individuals must realize that antiviral therapy can be, and typically is, very effective. This is the case even in those who have a low CD4 cell count and advanced disease, as long as drug resistance has not developed. CD4 cells are a type of immune cell used as a bellweather to judge the degree of HIV infection. The lower the count of CD4 cells in tests, the more advanced the infection. When should antiviral therapy be started? Until very recently, one of the biggest questions related to the management of HIV disease was the optimal time to start antiviral treatment. For some time, there had been very strong data demonstrating that therapy is appropriate for those with CD4 cells numbering less than 350 cells/mm3 in the blood. There have also long been strong recommendations to treat patients with select conditions regardless of their CD4 cell count, such as having HIV during pregnancy, in order to prevent transmission of HIV to the baby. Other cases that need immediate treatment are those who have HIV-associated renal disease or chronic hepatitis B infection where the antiviral treatment for HIV also treats the hepatitis virus.

Several large studies have shifted all guidelines around the world to recommending treatment of all HIV-infected individuals at the time of diagnosis no matter what the CD4 cell count.

Regardless, prior to initiating antiviral therapy, everything possible should be done to ensure that the patient is committed to the treatment, able to adhere to the regimen, and will follow up with his or her health care professional to assess whether medications are tolerated and working.

Guidelines for starting antiviral therapy have been proposed by panels of experts from several groups, including the Department of Health and Human Services (DHHS) (https://aidsinfo.nih.gov/) and International Antiviral Society-USA (IAS-USA). There are similar guidelines for treatment throughout Europe and by the World Health Organization for treatment in resource-limited countries. Until recently a recommendation supporting the start of therapy in those with CD4 cells greater than 500 cells was based upon evidence that ongoing viral replication, even in the setting of high CD4 cell counts, may be associated with damage to the brain, kidneys, heart, and possibly even liver. Along with this rationale, it was clear that newer regimens were easy to take, including a growing number of one-pill-per-day options, with minimal side effects. Another compelling argument that can be made for early therapy is the ability to reduce the risk of transmission to uninfected partners.

A study called HPTN 052 demonstrated that among couples in which one person is HIV-infected and the other is not, those who were on antiretroviral therapy were 96% less likely to transmit HIV to their uninfected partner than those not on treatment.

Finally, a large study was recently reported that demonstrated unequivocally that starting therapy even with a CD4 cell count of greater than 500 cells/mm3 was associated with less risk of disease progression than waiting until CD4 cells were less than 350 cells/mm3. This study was called the START study and demonstrated a major reduction in disease progression with early therapy with virtually no increased risk for side effects. Based upon START, HPTN 052 and other accumulated data, currently all major guidelines around the world, including those of the World Health Organization recommend that antiretroviral therapy be initiated in all HIV-infected patients at the time of diagnosis. It is worth noting that these recommendations for universal treatment of HIV-infected patients will be limited by resources available for antiviral treatment in resource-limited countries.

Before starting treatment, patients must be aware of the short- and long-term side effects of the drugs, including the fact that some long-term complications may not be known. Patients also need to realize that therapy is a long-term commitment and requires consistent adherence to the drugs. In addition, clinicians and patients should recognize that depression, feelings of isolation, substance abuse, and side effects of the antiviral drugs can all be associated with the failure to follow the treatment program.

SLIDESHOW

A Timeline of the HIV/AIDS Pandemic See Slideshow

Should patients with the flu- or mono-like illness of primary HIV infection be treated?

There are theoretical reasons why patients identified with HIV around the time they are first infected (primary, acute infection) may benefit from the immediate initiation of potent antiviral therapy. Preliminary evidence suggests that unique aspects of the body's immune response to the virus may be preserved by this strategy. It is thought that treatment during the primary infection may be an opportunity to help the body's natural defense system to work against HIV. Thus, patients may gain improved control of their infection while on therapy and perhaps even after therapy is stopped.

At one time, the hope was that if therapy was started very early in the course of the infection, HIV could be eradicated. Most evidence today, however, suggests that this is not the case, although research will certainly continue in the coming years in this area. Recent data demonstrated that a subset of those starting ART within the first weeks of infection were able to stop therapy after many years and maintain good viral control off treatment. While this response does not occur in the majority of similarly treated patients, the observations are intriguing and an area of ongoing research. Regardless, at least for now it is premature to think that early treatment may result in a cure, although other benefits may still exist, including avoiding the substantial damage to the immune system that occurs during the first weeks of infection.

In addition, these individuals have very high levels of virus in their blood and genital secretions, and early treatment might reduce their risk of transmitting HIV to others. There also is evidence that those who develop such symptoms during the early days of infection may be at greater risk of disease progression than those who become infected with minimal or no symptoms. Due to the absence of definitive data, guidelines vary. Because doctors now recommend all patients initiate therapy at the time of diagnosis, it is generally recommended that patients with primary infection be offered early therapy.

What about treatment for HIV during pregnancy?

One of the greatest advances in the management of HIV infection has been in pregnant women. Prior to antiviral therapy, the risk of HIV transmission from an infected mother to her newborn was approximately 25%-35%. The first major advance in this area came with studies giving ZDV (zidovudine) after the first trimester of pregnancy, then intravenously during the delivery process, and then after delivery to the newborn for six weeks. This treatment showed a reduction in the risk of transmission to less than 10%. There is strong data that women who have viral suppression during pregnancy have a very low risk of transmitting HIV to their baby, perhaps even less than 1%. Current recommendations are to advise HIV-infected pregnant women regarding both the unknown side effects of antiviral therapy on the fetus and the promising clinical experience with potent therapy in preventing transmission. In the final analysis, however, pregnant women with HIV should be treated essentially the same as nonpregnant women with HIV. The choice of medications in this situation should be determined after consultation with an expert in treating HIV-infected pregnant women.

All HIV-infected pregnant women should be managed by an obstetrician with experience in dealing with HIV-infected women. Maximal obstetric precautions to minimize transmission of the HIV virus, such as avoiding scalp monitors and minimizing labor after rupture of the uterine membranes, should be observed. In addition, the potential use of an elective Caesarean section (C-section) should be discussed, particularly in those women without good viral control of their HIV infection where the risk of transmission may be increased. Breastfeeding should be avoided if alternative nutrition for the infant is available since HIV transmission can occur by this route. When breastfeeding is done, it should be in conjunction with antiretroviral therapy for the mother if at all possible. Updated guidelines for managing HIV-infected women are updated on a regular basis and can be found at https://aidsinfo.nih.gov/.

QUESTION

What is HIV? See Answer

What can be done for people who have severe immunosuppression?

Although one goal of antiviral therapy is to prevent the development of immune suppression, some individuals are already immunosuppressed when they first seek medical care. In addition, others may progress to that stage as a result of resistance to antiviral drugs. Every effort must be made to optimize antiviral therapy in these patients. In addition, certain specific antibiotics should be initiated, depending on the number of CD4 cells, to prevent the complications (that is, the opportunistic infections) that are associated with HIV immunosuppression. Guidelines for the prevention of opportunistic infections can be found at https://aidsinfo.nih.gov/.

In summary, patients with a CD4 cell count of less than 200 cells/mm3 should receive preventative treatment against Pneumocystis jiroveci with trimethoprim/sulfamethoxazole (Bactrim, Septra), given once daily or three times weekly. If they are intolerant to that drug, patients can be treated with an alternative drug such as dapsone or atovaquone (Mepron). Those patients with a CD4 cell count of less than 100 cells/mm3 who also have evidence of past infection with Toxoplasma gondii, which is usually determined by the presence of Toxoplasma antibodies in the blood, should receive trimethoprim/sulfamethoxazole. Toxoplasmosis is an opportunistic parasitic disease that affects the brain and liver. If a person is using dapsone to prevent Pneumocystis jiroveci, pyrimethamine and leucovorin can be added once a week to dapsone to prevent toxoplasmosis. Finally, patients with a CD4 cell count of less than 50 cells/mm3 should receive preventive treatment for Mycobacterium avium complex (MAC) infection with weekly azithromycin (Zithromax), or as an alternative, twice daily clarithromycin (Biaxin) or rifabutin (Mycobutin). MAC is an opportunistic bacterium that causes infection throughout the body. Many of these drugs can be stopped if initial antiviral therapy results in good viral suppression and sustained increases in CD4 cells.

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Medically Reviewed on 12/18/2019
References
Branson, B.M., Handsfield, H.H., Lampe, M.A., et al. "Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings." MMWR 55 (2006): 1-17.

DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. "Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents." Washington D.C.: Department of Health and Human Services, 2018. <https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf>
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