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Once the immune system has failed to a significant degree, it becomes necessary to try to prevent the occurrence of the most common opportunistic infections (OI), or prevent their return after a first occurrence.

OI prevention or "prophylaxis" should be considered when CD4+ counts are in or nearing a danger zone (for example, the risk of PCP becomes high at CD4+ count of 300 or below, and the risk of CMV and MAI increase rapidly when the CD4+ falls below 100).

Careful and timely use of medication can prevent PCP altogether. As the incidence of tuberculosis (TB) rises among HIV-positive people, testing and possibly preventive treatment is recommended. Similar preventive treatment is rapidly becoming available for other infections as well.

In advanced HIV disease, an infected person often must try to treat or prevent several different opportunistic infections at the same time. This can lead to difficult choices, since many medications can interact with each other.

The key to successful intervention is comprehensive inclusion—doing all of the things that make sense in your individual situation. The biggest mistake is to dogmatically choose one approach over the others. HIV is not a political debate or a matter of opinion—it is a life threatening illness. Every decision about treatment has consequences. Each infected person has little room for mistakes. It makes no sense to bet your life on any single philosophy of medicine.

Resistance develops more rapidly in people with detectable viral loads. Studies have shown that there is a correlation between low viral loads and duration of response as it is more difficult for the virus to mutate.