There is currently no cure for HIV infection. Treatment consists of highly active antiretroviral therapy, or HAART. This has been highly beneficial to many HIV-infected individuals since its introduction in 1996, when the protease inhibitor-based HAART initially became available. Current HAART options are combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of antiretroviral agents. Typically, these classes are two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI).
There is no empirical evidence for withholding treatment at any stage of HIV infection, and death rates are almost twice as high when therapy is deferred (until the CD4 count falls below 500) compared to starting therapy when the CD4 count is above 500. However, the timing for starting HIV treatment is still subject to debate.
The United States Panel on Antiretroviral Guidelines for Adults and Adolescents in 2009 recommended that antiretroviral therapy should be initiated in all patients with a CD4 count less than 350, with treatment also recommended for patients with CD4 counts between 350 and 500. However, for patients with CD4 counts over 500, the expert Panel was evenly divided, with 50% in favor of starting antiretroviral therapy at this stage of HIV disease, and 50% viewing initiating therapy at this stage as optional. They noted that "Patients initiating antiretroviral therapy should be willing and able to commit to lifelong treatment and should understand the benefits and risks of therapy and the importance of adherence".
New classes of drugs such as entry inhibitors provide treatment options for patients infected with viruses already resistant to common therapies, although they are not widely available and not typically accessible in resource-limited settings. Because AIDS progression in children is more rapid and less predictable than in adults, in particular, in young infants, more aggressive treatment is recommended for children than adults. In developed countries where HAART is available, doctors assess their patients thoroughly: measuring the viral load, how fast CD4 declines, and patient readiness. They then decide when to recommend starting treatment.
HAART neither cures the patient nor uniformly removes all symptoms; high levels of HIV-1, often HAART-resistant, return if treatment is stopped. Moreover, it would take more than a lifetime for HIV infection to be cleared using HAART. Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to a large reduction in HIV-associated morbidity and mortality in the developed world. One study suggests the average life expectancy of an HIV infected individual is 32 years from the time of infection if treatment is started when the CD4 count is 350/µL. Life expectancy is further enhanced if antiretroviral therapy is initiated before the CD4 count falls below 500/µL.
In the absence of HAART, progression from HIV infection to AIDS has been observed to occur at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months. However, HAART sometimes achieves far less than optimal results, in some circumstances being effective in less than fifty percent of patients. This is due to a variety of reasons such as medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. However, non-adherence and non-persistence with antiretroviral therapy is the major reason most individuals fail to benefit from HAART.
The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues along with side effects that create intentional non-adherence also contribute to this problem. The side effects include lipodystrophy, dyslipidemia, insulin resistance, an increase in cardiovascular risks, and birth defects.
Anti-retroviral drugs are expensive, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS. Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. Unfortunately, only a vaccine is thought to be able to halt the pandemic. This is because a vaccine would cost less, thus being affordable for developing countries, and would not require daily treatment. However, after over 20 years of research, HIV-1 remains a difficult target for a vaccine.
HIV latent reservoir
Despite the success of highly active antiretroviral therapy (HAART) in controlling HIV infection and reducing HIV-associated mortality, current drug regimens are unable to completely eradicate HIV infection. Many people on HAART achieve suppression of HIV to levels below the limit of detection of standard clinical assays for many years. However, upon withdrawal of HAART, HIV viral loads rebound quickly with a concomitant decline in CD4+ T-Cells, which, in most cases, without a resumption of treatment, leads to AIDS.
To successfully reproduce itself, HIV must convert its RNA genome to DNA, which is then imported into the host cell's nucleus and inserted into the host genome through the action of HIV integrase. Because HIV's primary cellular target, CD4+ T-Cells, function as the memory cells of the immune system, integrated HIV can remain dormant for the duration of these cells' lifetime. Memory T-Cells may survive for many years and possibly for decades. The latent HIV reservoir can be measured by co-culturing CD4+ T-Cells from infected patients with CD4+ T-Cells from uninfected donors and measuring HIV protein or RNA.
The failure of vaccine candidates to protect against HIV infection and progression to AIDS has led to a renewed focus on the biological mechanisms responsible for HIV latency. A limited period of therapy combining anti-retrovirals with drugs targeting the latent reservoir may one day allow for total eradication of HIV infection.