The majority of HIV-infected individuals are able to regulate viral replication for many years because of an effective immune response; however, in the current era of potent combination antiretroviral therapy (ART), the recommendation is to initiate ART in all HIV-infected people and not to monitor with serial blood testing and clinical assessments in patients who are off therapy. Without ART, there is a steady decline over time of CD4 numbers and slow destruction of immunity leading to gradual onset of constitutional symptoms followed by opportunistic infections and malignancies. Patients may progress through the stages consecutively, but in many cases may move to a stage, skipping a clinical stage in between. Individuals do not revert to a previous stage even if treated.
ART reduces HIV replication to levels that are undetectable by laboratory assays. This allows the restoration of even advanced immune deficiency to safe levels in the vast majority of treated persons and the restoration and maintenance of health in a previously progressive and uniformly fatal syndrome. ART can also reduce HIV transmission and prevent infection after blood or sexual exposure (post-exposure prophylaxis). As long as appropriate ART is taken as prescribed without default, the benefits of the viral suppression will be sustained. Poor adherence is the most common cause for failure of a regimen due to development of drug resistance, leading to breakthrough replication and persistent immune damage. Under these circumstances, a new regimen must be found with non-resistant agents, which can then, if taken correctly, lead to viral suppression once more. The central goal of HIV therapy then is maximal suppression of viral replication sufficient to prevent the selection of viral resistance mutations, and long-term adherence without therapy interruptions remains the key to the efficacy of all HIV regimens.
Most patients on ART achieve virological suppression within 3 to 6 months. Viral rebound rates have decreased over the years, and the risk decreases with increasing duration of viral suppression. A UK-based cohort study of over 16,000 HIV-positive persons found that a substantial proportion of patients on ART will not experience viral rebound over their lifetime (approximately 1% of men who have sex with men aged 45 years and older experienced viral rebound per year). Rates of viral suppression nearly tripled in the US from 32% in 1997 to 86% in 2015, mainly due to improvement in ART regimens over the years.
Globally, mortality peaked in 2006 with 1.95 million deaths, and has since decreased to 0.95 million deaths in 2017. This figure dropped to 770,000 in 2018. The all-cause mortality rate in the first 3 years after starting ART is declining. The rate was lower for those who began treatment between the years 2008-2010 compared with those who began treatment from 2000-2003. This is likely to be due to factors including the availability of less toxic drugs, improved adherence to drug regimens, and better management of comorbidities. Life expectancy after starting ART has improved over time. Life expectancy has increased to approximately 63-67 years of age (depending on country and sex) for patients aged 20 years who started therapy from 2008-2010; however, it is still lower than in the general population. Cancer mortality among people with HIV infection is much higher than in the US general population. Approximately 10% of deaths are due to cancer, most commonly non-Hodgkin's lymphoma, lung cancer, and liver cancer.
A small proportion of individuals are able to control HIV viral load without assistance of ART. Many have low-to-undetectable viral loads and well-preserved CD4 counts for many years. This appears in part to be due to a robust immunity to HIV. However, even these individuals are likely to benefit from consistent and uninterrupted use of ART.
Two cases of remission have been reported in patients with HIV-1 infection after stem-cell transplantation with donor stem cells from individuals with a homozygous mutation in the HIV coreceptor CCR5. The latest case was reported in the UK in March 2019, ten years after the first case. The man has been in remission for 18 months after undergoing an allogeneic haematopoietic stem-cell transplant for Hodgkin's lymphoma using cells from a CCR5delta32/delta32 donor and then stopping ART. While these cases help further HIV research, the clinical implications are currently unknown, but support the development of HIV remission strategies based on preventing CCR5 expression.
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