Ways of attacking HIV

HIV has a complex life-cycle that involves several steps. Disease progression occurs when the virus replicates (reproduces) and infects new cells. The key goal of antiretroviral therapy is to slow – or ideally stop – HIV replication and enable recovery of the immune system.

Antiretroviral drugs, targeting different steps in the viral life-cycle, are the mainstay of HIV treatment. These include, but are not limited to:

• Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs and NtRTIs).
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
• Protease inhibitors.
• Integrase inhibitors.
• Fusion inhibitors.
• CCR5 inhibitors.

There are a number of other candidate drugs in clinical trials, including one in a class called 'maturation inhibitors', as well as innovations in immune-based strategies.

The standard of care for anyone on antiretroviral treatment is highly active antiretroviral therapy (HAART) using drugs with at least two different mechanisms of action (for example, two NRTIs plus either an NNRTI or a protease inhibitor). Over time, HIV can develop mutations that make it resistant to drugs. For this reason, people who have more treatment experience may need more drugs to construct an effective regimen. By targeting multiple steps in the viral life-cycle simultaneously, the emergence of resistance can be slowed or prevented.

Researchers have also explored other approaches for treating HIV, such as inhibiting cellular factors the virus needs for its replication, gene therapy that protects cells from infection, and removal of cells that are already infected. Many of these approaches are experimental and some remain purely theoretical. But there is evidence that complementary therapies such as nutrient supplements – used in conjunction with antiretroviral therapy – can improve the overall health of people with HIV.

Since the advent of effective combination antiretroviral therapy in the mid-1990s, researchers have discovered much about how best to treat HIV, and treatment has shifted from managing opportunistic illness to suppressing the virus to the greatest extent possible. New studies are showing that even at CD4 cell counts between 350 and 500 cells/mm³, there is a greater risk of morbidity and mortality from non-AIDS illnesses.

While viral load suppression is considered an indicator of effective therapy, the ultimate goal of treatment is to preserve immune function, increase disease-free survival, and reduce mortality. Once HIV replication is controlled, a person’s CD4 cell count usually rises over time, but this occurs more slowly in some patients. Researchers are studying various ways to promote immune system reconstitution and HIV-specific immune response.

Effective antiretroviral therapy has dramatically improved survival and lowered the incidence of opportunistic illnesses and other conditions related to immune suppression in people with HIV. But much remains to be learned about long-term treatment, including whether it is possible to completely eradicate HIV from the body.