Figure 2.1. Rash in acute HIV.

    Because of a precipitous drop in CD4 lymphocytes that may be observed during acute HIV infection, some individuals can present during this phase with opportunistic infections, such as PCP or thrush.

    After the acute retroviral syndrome resolves, patients may be asymptomatic during a plateau period in the infection which can last for years. Later symptoms vary depending on disease stage and the degree of immunologic dysfunction. Conditions associated with significant immune suppression and that are clinically AIDS-defining are shown in table 2.2.

    Conditions commonly seen by internists in the outpatient setting that are not AIDS-defining conditions but should prompt consideration of HIV testing include Herpes zoster, seborrheic dermatitis, thrush, or recurrent vaginal candidiasis—all occur commonly in those without HIV infection, but the incidence and severity in patients with HIV tend to be greater. Furthermore, for those seeking care for a sexually transmitted infection, HIV testing should be offered during each visit for a new complaint because the mode of transmission is the same. Tuberculosis can present in HIV-infected individuals even with a relatively high CD4 count, and all persons initiating treatment for TB should be tested for HIV. Many HIV-infected persons will be asymptomatic, however, underscoring the need for routine screening.

ESTABLISHING THE DIAGNOSIS

The CDC guidelines for HIV testing published in the September 2006 MMWR recommend one-time routine opt-out testing for patients aged 13–64 years in all healthcare settings unless the patient declines. CDC guidelines also recommend annual testing among those who engage in high-risk behavior. It is important to recognize that the notion of high-risk groups has been replaced by that of high-risk behavior and that many people who engage in high-risk behaviors do not disclose these behavior. A study of MSM in New York City found that about 40% of those engaging in high-risk behaviors had not disclosed attraction to or having had sex with other men to their healthcare providers.

    To diagnose established infection, HIV antibody testing should be performed. If the initial enzyme-linked immunosorbent assay (ELISA) is positive, a confirmatory Western blot assay is performed. A Western blot is interpreted as positive if at least two of three viral antigens (p24, gp41, gp120/160) are present, and negative if there is an absence of bands (Figure 2.2). An “indeterminate” result (any positive band or bands but not meeting criteria for positive) may indicate either a false-positive ELISA (e.g., caused by pregnancy, autoimmune disease, lymphoma, recent influenza vaccination, prior participation in HIV vaccine trials, and other causes) or seroconversion in progress. In cases of seroconversion in progress, the follow-up Western blot will generally be fully positive within 1 month, and HIV RNA (viral load) will typically be detectable at very high levels (>100,000 copies/mL). Viral loads should not be sent as routine screening tests for established HIV infection, since false positives at low levels (such as <1000 copies/mL) are not uncommon and can lead to unnecessary repeat testing and anxiety. In cases where acute HIV infection is suspected, however, a viral load should be performed because seroconversion may take several weeks (the “window period”). With the increasing sensitivity of the HIV antibody screening ELISA tests some patients with acute HIV may present with fully negative Western blot (no bands) and positive ELISA, so it is important to use HIV viral load testing in any case where acute HIV is suspected. New combination antigen-antibody screening tests provide increased sensitivity at early stages of infection with increased specificity in low-prevalence populations, but these are not yet widely utilized at clinical sites.

    Rapid HIV testing is becoming increasingly utilized because of its convenience, low cost, and accuracy. The rapid HIV test can be performed on both blood specimens and oral secretions, and a negative test carries the same implications as a negative ELISA; a positive rapid test needs to be confirmed with standard ELISA/Western blot testing.

    Rapid testing has been associated with a relatively high number of false-positive results when performed in low-prevalence settings; hence, reactive results should be communicated as “preliminary” or “inconclusive” with a need for confirmatory testing. This disadvantage notwithstanding, the CDC continues to recommend rapid testing because it increases the number of persons tested and the number of persons who actually receive their test results.

    The CDC recommends opt-out HIV screening as a part of the routine panel of prenatal screening tests for all pregnant women without a special written consent being required. Repeat screening in the third trimester should be performed in geographic areas with an elevated HIV incidence rate (≥17 per 100,000 person years in women aged 15–45, in 2004: the areas of Alabama, Connecticut, Delaware, the District of Columbia, Florida, Georgia, Illinois, Louisiana, Maryland, Massachusetts, Mississippi, Nevada, New Jersey, New York, North Carolina, Pennsylvania, Puerto Rico, Rhode Island, South Carolina, Tennessee, Texas, and Virginia).

INITIAL EVALUATION

The initial evaluation of an individual with HIV infection should consist of complete history including a detailed social history, physical examination, and laboratory evaluation. In addition to making the diagnosis, the stage of HIV illness should be determined and the presence of other possible concurrent infections should be determined.

    Initial laboratory evaluation should include HIV antibody testing (if the original laboratory test is not available for review), CD4 count, and HIV RNA (viral load). To evaluate for bone marrow suppression as well as underlying liver or kidney disease, a complete blood count, chemistry, and liver function tests should be obtained. A urinalysis should be obtained (to evaluate for the presence of HIV-associated nephropathy, which would be an indication for early initiation of therapy). In addition, a fasting lipid panel and glucose measurement are included in the initial evaluation. Laboratory findings, such as hyperlipidemia, renal or liver dysfunction, anemia or thrombocytopenia, could potentially alter the selection of an antiretroviral regimen.

    Initial evaluation should also include a screening test for syphilis (rapid plasma reagin [RPR] or treponemal IgG), toxoplasmosis IgG, cytomegalovirus (CMV) IgG, and hepatitis serologies (including hepatitis A antibody, hepatitis B surface antigen and antibody, hepatitis B core antibody, and hepatitis C antibody). In addition, a tuberculin skin test (TST) or interferon-γ release assay (IGRA) (unless there is a history of prior tuberculosis or positive TST or IGRA) should be obtained. If a TST is performed when the patient’s CD4 is <200 cells/mm³, it should be repeated when the CD4 rises to >200 cells/mm³ on treatment. If the TST or IGRA is positive or there are pulmonary symptoms, a chest x-ray should be obtained. Women should undergo a Papanicolaou (Pap) smear, and one should consider baseline testing for gonorrhea and chlamydia. Although there are no formal CDC recommendations for performing annual anal Pap smears for MSM, many experts in the field support this practice. New York State issued formal guidelines for anal dysplasia screening that include annual anal Pap smear testing for HIV-positive MSM and women, and high-resolution anoscopy for patients with evidence of dyplasia on Pap smear. Finally, recommendations from the DHHS suggest obtaining baseline genotypic resistance testing (a test that requires an HIV RNA >1000 copies/mL to be run). Laboratory tests recommended for initial assessment and for ongoing care of HIV-infected patients are found in table 2.3.

    Social issues can powerfully affect the outcome of treatment by influencing adherence and access to care: substance use, mental illness, social support, economic stressors, ongoing high-risk behaviors, and family-planning issues should all be assessed. Given the stigma that still surrounds the diagnosis of HIV, it is worth exploring with patients whether they have disclosed the diagnosis to anyone else and, if so, to whom. Education about HIV risk behaviors and prevention of HIV transmission to others should be provided initially and then subsequently at each patient visit.

INITIATION OF THERAPY

The optimal time to start antiretrovirals (ARVs)—the medications directly targeting the replication of HIV—remains uncertain. Although potent and well-tolerated medications are available, concerns remain about long-term side effects, selection of drug-resistant virus, and cost. For many years the guidelines suggested initiating therapy for all those with symptomatic HIV disease or a CD4 count <200 cells/mm³ and considering therapy for those with a CD4 count <350 cells/mm³ or viral load >100,000 copies/mL. As of 2013, the US guidelines recommend:

CO-INFECTIONS

Those at risk for HIV infection are also at risk for other chronic infections with similar modes of transmission. Co-infections of particular clinical interest in the HIV-infected person include hepatitis B (HBV), hepatitis C (HCV), and syphilis.

    Chronic HBV infection develops more frequently in HIV co-infected patients than in those with HBV alone. Although HIV infection affects the natural course of HBV infection, HBV co-infection does not appear to have an effect on CD4 depletion or progression to AIDS. Many agents used to treat HBV are also active against HIV. Treating only HBV may lead to drug-resistant HIV. For this reason, those requiring treatment for HBV should be started on a standard HIV ARV regimen with two agents active against both HIV and HBV (such as tenofovir and emtricitabine).

    HIV and HCV co-infection can accelerate the clinical course of both infections. Although immunologic decline from HIV disease may be more rapid and CD4 responses blunted, HCV RNA levels are increased in these patients, and they are more likely to develop cirrhosis or decompensated liver disease. For many years management of chronic HCV infection with interferon-based therapy has been difficult and often unsuccessful. However, newer agents for HCV treatment that are recently released offer increased rates of success (cure of HCV) and the possibility of less-toxic interferon-sparing therapy. Patients co-infected with HIV and HBV/HCV would benefit from expert consultation from providers experienced in assessment and management of both these infections.

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