Prognosis
The majority of people with HIV are able to suppress viral replication with antiretroviral therapy (ART) for many years. 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. The life expectancy of people with HIV taking ART has increased substantially over the last 25 years.[160] Approximately 50% of the global population of people living with HIV is aged >50 years.[91]
Virological suppression
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.[161]
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).[162] 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.[163]
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.
Mortality
Globally, mortality peaked in 2004 with 2 million deaths, and has since decreased to 650,000 deaths in 2021. UNAIDS: in danger: UNAIDS global AIDS update 2022 Opens in new window Rates of cause-specific mortality declined between 1996 and 2020, with the largest reductions in rate of AIDS-related mortality, as well as cardiovascular-related and liver-related mortality.[164] In the US, HIV-related deaths decreased by 48% from 2010 to 2017 (from 9.1 to 4.7 per 1000 people with diagnosed HIV).[165]
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 and 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.[166] For those with a CD4 count of at least 500 cells/microlitre who started ART after 2015 (when guidelines began to recommend ART for all patients, regardless of CD4 count), life expectancy was only a few years lower than that in the general population (3.8 years lower in women, and 1.5 years lower in men). Life expectancy estimates were significantly lower in people with low CD4 counts at the start of follow-up.[160]
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 to 2010; however, it is still lower than in the general population.[167]
Cancer mortality among people with HIV 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.[168]
The most common cause of death in sub-Saharan Africa between 2008 and 2018 was tuberculosis. Opportunistic malignancies accounted for between 1.2% and 9.8% of deaths.[169]
Remission or cure
Seven cases of remission have been reported in people with HIV-1 after stem-cell transplantation with donor stem cells from individuals with a mutation in the HIV coreceptor CCR5 (as of July 2024).[170]
The first case, known as the Berlin patient, was reported in Berlin in 2007 and he was in remission for 12 years before dying of recurrent leukaemia in 2020.[171]
The second case, known as the London patient, was reported in the UK in 2019 and is still currently in remission after undergoing an allogeneic haematopoietic stem-cell transplant for Hodgkin's lymphoma using cells from a CCR5delta32/delta32 donor and then stopping ART.[171]
The first case of remission in a woman was reported in early 2022 after the woman received a dual stem cell transplant (i.e., umbilical cord blood transplant combined with a half-matched bone marrow transplant) for the treatment of acute myelogenous leukaemia. The woman stopped ART 37 months after the transplant and had no detectable HIV levels for 14 months after.[172]
The seventh case (second Berlin patient) was reported in 2024. The patient was the first to have received donor stem cells with just a single CCR5-delta 32 mutation instead of a double mutation like other cases. This is significant because it is an important difference to other cases as the cells were not fully immune to HIV.[170]
While these cases help further HIV research, the clinical implications are currently unknown, but support the development of HIV remission strategies based on various immunological interventions and/or therapies to reduce the HIV reservoir.
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