HIV and AIDS

[1]

The one-minute consultant answer

HIV is a retrovirus (HIV-1 is responsible for the global pandemic; HIV-2 is confined mainly to West Africa and runs a more indolent course) that infects and progressively depletes CD4-positive T-lymphocytes, producing a state of progressive cell-mediated immunodeficiency whose end stage is AIDS. The transforming principle of modern management is that antiretroviral therapy (ART) should be started in every person living with HIV regardless of CD4 count — a strategy validated by the START trial, which showed that immediate ART in asymptomatic patients with CD4 above 500 reduced serious AIDS and non-AIDS events by 57 per cent compared with deferring until CD4 fell below 350 [1]. Standard first-line therapy is a single-tablet regimen of tenofovir plus emtricitabine plus an integrase strand transfer inhibitor (dolutegravir or bictegravir), taken once daily, that achieves viral suppression (HIV RNA below 50 copies per millilitre) in over 90 per cent of patients within 12 to 24 weeks [7].

Once viral load is undetectable, the risk of sexual transmission is effectively zero — the principle of Undetectable equals Untransmittable (U equals U), confirmed by the PARTNER and PARTNER2 studies, which recorded zero phylogenetically linked transmissions across tens of thousands of condomless sex acts [3][4]. The physician's job is therefore fourfold: diagnose (4th-generation combination antigen/antibody test plus HIV RNA viral load), treat (start ART immediately, achieve and maintain viral suppression), prevent opportunistic infections by CD4 threshold (co-trimoxazole below 200; azithromycin below 50), and manage the long-term comorbidities of a now-chronic disease (cardiovascular disease, bone disease, renal disease, malignancy, neurocognitive impairment). Treatment interruption is harmful and must not be attempted [9].

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1. [1]Lundgren JD, Babiker AG, Gordin F, et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection N Engl J Med, 2015.PMID 26192873
2. [2]Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy N Engl J Med, 2011.PMID 21767103
3. [3]Rodger AJ, Cambiano V, Bruun T, et al. Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy JAMA, 2016.PMID 27404185
4. [4]Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study Lancet, 2019.PMID 31056293
5. [5]Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men N Engl J Med, 2010.PMID 21091279
6. [6]Danel C, Moh R, Gabillard D, et al. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa N Engl J Med, 2015.PMID 26193126
7. [7]Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection N Engl J Med, 2013.PMID 24195548
8. [8]Sabin CA, Worm SW, Weber R, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration Lancet, 2008.PMID 18387667
9. [9]El-Sadr WM, Lundgren J, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment N Engl J Med, 2006.PMID 17135583
10. [10]Zash R, Holmes L, Diseko M, et al. Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana N Engl J Med, 2019.PMID 31329379