_______________________________________________________________________ HIV/AIDS: An Update
A variety of clinical syndromes may supervene at this juncture including dementia, peripheral neuropathy, wasting syndrome, and chronic diarrhea. In the United States, the most com- mon AIDS-defining opportunistic diseases are: PCP, Kaposi sarcoma, candidiasis, cryptococcosis, cryptosporidiosis, CMV, atypical mycobacteriosis, systemic herpes, toxoplasmosis, and tuberculosis [50]. In the absence of effective therapy, the average survival is approximately 3.5 years after the patient’s CD4 count has reached 200 cells/mcL and 1.5 years for the patient who has developed an AIDS-defining diagnosis. The natural history and the prognosis for the patient with chronic HIV infection have been dramatically altered by antiretroviral therapy, with studies finding that the average life expectancy of an individual with a CD4 count of greater than 500 cells/mcL on sustained long- term ART is nearly the same as the general population [28; 29]. MANAGEMENT OF HIV INFECTION Primary care providers in consultation with specialists are playing an increasing role in the care of HIV-infected individu- als. It is not possible for all care to be delivered by infectious disease and oncology specialists. Moreover, with early ART and prophylaxis for opportunistic infections, HIV disease shares features of other multisystem, chronic diseases characterized by acute exacerbations and end-stage manifestations. Primary care providers should conduct risk factor assessment of their patients and, when appropriate, screen for HIV infec- tion with pretest and post-test counseling. For persons who test positive, information on available medical and mental health services should be provided as well as guidance for contacting sexual or needle-sharing partners. Patients with HIV infection should be seen at regular intervals by a primary care provider to perform periodic physical examinations, monitor prognostic markers (e.g., CD4 count, viral load), initiate and monitor antiviral and prophylactic therapy, and provide supportive counseling. Specialists should be consulted for patients intoler- ant of standard drugs, those in need of systemic chemotherapy, and those with complicated opportunistic infections. In some cases, a single specialist consultation with follow-up to the primary care physician will provide the needed expertise while ensuring continuity of care. Standard laboratory tests for patients with HIV infection may include: • HIV serology • Quantitative HIV RNA • CD4 count • Complete blood count (CBC) • Chest x-ray • Hepatitis serology and liver chemistry panel • Syphilis serology
• Purified protein derivative (PPD) skin test to diagnose tuberculosis ANTIRETROVIRAL THERAPY HIV disease is treated with therapeutic regimens consisting of a combination of three or more antiretroviral drugs. Cur- rent ART does not cure HIV infection but does suppress viral replication and allow immune system recovery sufficient to restore a sense of well-being and regain the capacity to avoid opportunistic infections. Since 2016, the WHO has recom- mended that all people living with HIV be provided lifelong ART, including children, adolescents, adults, and pregnant and breastfeeding women, regardless of clinical status or CD4 cell count [5]. In 2024, the U.S. Department of Health and Human Services (HHS) released updated guidelines for ART, a collaborative effort of a Panel comprised of more than 50 mem- bers with expertise in HIV care and research, and represented by members from the U.S. Food and Drug Administration (FDA), Health Resource and Services Administration (HRSA), and National Institutes of Health (NIH), among others [43]. ART (also known as cART or HAART) consists of a combina- tion of three or more drugs selected from nine major classes of agents, including [42]: • Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
• Protease inhibitors (PIs) • Fusion inhibitors (FIs)
• Integrase strand transfer inhibitors (INSTIs) • Chemokine (C-C motif) receptor 5 (CCR5) antagonists • gp120 attachment inhibitors • Capsid inhibitors • Post-attachment inhibitors
Initiated in 1995 in the United States, antiretroviral therapy regimens have been effective in dramatically decreasing HIV- related morbidity and mortality and should be considered for all HIV-infected persons. In addition to combination therapy, the sequencing of drugs and the preservation of future treat- ment options are also important. A significant proportion of patients starting ART are infected with drug-resistant strains of HIV, which may lead to suboptimal virologic responses. Therefore, pretreatment genotypic resistance testing should be used to guide selection of the most optimal initial regimen. The 2024 guidelines recommend initial ART regimens based on an oral second-generation INSTI plus two NRTIs. If INSTI resistance is possible and/or if genotype results are not yet avail- able, a boosted PI in combination with two NRTIs is recom- mended [42]. The goal of these regimens is to effectively reduce HIV-associated morbidity, prolong the duration and quality of survival, restore and preserve immunologic function, and prevent HIV transmission while also avoiding drug resistance.
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MDCT2026
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