The Changing Face of HIV

S3 HIV was first identified as the causative agent of AIDS in the early to mid 1980s. At that time, life expectancy for someone infected with HIV was very limited, and treatments for AIDS-defining opportunistic infections such as Pneumocystis carinii pneumonia and Mycobacterium avium complex provided an average survival gain of only 3.5 months. Fortunately, mortality and morbidity from HIV infection declined precipitously in the mid 1990s, largely due to the development of combination antiretroviral therapy. As a result, HIV infection is now largely a chronic, medically managed condition, and, therefore, greater emphasis must be placed on managing other intercurrent diseases, such as hypertension or diabetes in the HIV-positive population. The development of antiretroviral (ARV) drugs targeting HIV-1 was rapid. Since 1990, 5 classes of drugs have been approved by the Food and Drug Administration, comprising 24 different compounds; 2 new classes (an integrase inhibitor and CCR5 antagonist) were recently approved and are now commercially available in the United States. The focus on new agents is crucial because the viral replication process is error prone, and the resulting mutations may rapidly confer a selective advantage to a drug-resistant virus. Incomplete viral suppression and resistance generally lead to clinical deterioration over time, ultimately requiring a switch in medication to bring about control of viral replication. Evidence-based recommendations that include initial therapy with a combination of 3 or more drugs— typically a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs), or a protease inhibitor (PI) plus 2 NRTIs, along with guidance on when to start, are now in place to reduce the likelihood of treatment failure. A number of studies show that a high level of adherence to the medication regimen is required for viral suppression and prevention of resistance. In one recent study, 80% of patients with 95% to 100% NNRTI adherence achieved undetectable viral loads (plasma HIV RNA <50 copies/mL), compared with <10% of patients with 0% to 49% adherence; each 10% increment in adherence was associated with a 25% decrease in the odds of NNRTI resistance (P = .04). Data on unboosted PIs were consistent with increased resistance at adherence levels just below that required to achieve complete viral suppression. Another study found a 1.9-fold greater likelihood of resistance if adherence decreased to 90% and a 2.4-fold greater likelihood with 80% adherence. Although the benefits of adherence are clear, this is a substantial challenge for patients. Apart from the pill burden and drug side effects, lifetime traumatic events, mental illness, coping strategies, substance abuse, and the lack of insurance have all been shown to impact adherence. The personal and socioeconomic issues that influence treatment adherence are likely to affect different individuals to different degrees. Relationship with the health care system, stigma, and disclosure all can have an impact. The demographics of the current population with HIV infection are much more heterogeneous than in the early days of the epidemic. HIV/AIDS was first characterized in the gay, white male populations of New York and San Francisco. Now it is a worldwide epidemic affecting people from all walks of life. In the United States, the latest available data from the Centers for Disease Control and Prevention show that, of those diagnosed with HIV/AIDS in 2005, 49% were African American and 26% were women. This is in stark contrast to the early stages of the epidemic (from 1981 to 1995) when African American patients represented 34.6% of AIDS cases and women only 15% of cases. The modes of transmission of HIV have also changed; from 1981 to 1995, 10.1% of AIDS cases were acquired through heterosexual contact, whereas from 2001 to 2004, this proportion had increased to 30.1%. These facts further confound the issues faced by health care providers. Although genetic, gender, and socioeconomic factors can all play a part in how well a patient responds virologically and immunologically to a particular regimen, these factors can also affect the incidence and severity of drug toxicity, and, along with