Management of HIV/AIDS
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection.[1] There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death.[2] HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.[3]
Treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS is increasingly rare. Anthony Fauci, former head of the United States National Institute of Allergy and Infectious Diseases, has written, "With collective and resolute action now and a steadfast commitment for years to come, an AIDS-free generation is indeed within reach." In the same paper, he noted that an estimated 700,000 lives were saved in 2010 alone by antiretroviral therapy.[4] As another commentary in The Lancet noted, "Rather than dealing with acute and potentially life-threatening complications, clinicians are now confronted with managing a chronic disease that in the absence of a cure will persist for many decades."[5]
The United States Department of Health and Human Services and the World Health Organization[6] (WHO) recommend offering antiretroviral treatment to all patients with HIV.[7] Because of the complexity of selecting and following a regimen, the potential for side effects, and the importance of taking medications regularly to prevent viral resistance, such organizations emphasize the importance of involving patients in therapy choices and recommend analyzing the risks and the potential benefits.[7]
The WHO has defined health as more than the absence of disease. For this reason, many researchers have dedicated their work to better understanding the effects of HIV-related stigma, the barriers it creates for treatment interventions, and the ways in which those barriers can be circumvented.[8][9]
Treatment guidelines[edit]
Initiation of antiretroviral therapy[edit]
Antiretroviral drug treatment guidelines have changed over time. Before 1987, no antiretroviral drugs were available and treatment consisted of treating complications from opportunistic infections and malignancies. After antiretroviral medications were introduced, most clinicians agreed that HIV positive patients with low CD4 counts should be treated, but no consensus formed as to whether to treat patients with high CD4 counts.[26]
In April 1995, Merck and the National Institute of Allergy and Infectious Diseases began recruiting patients for a trial examining the effects of a three drug combination of the protease inhibitor indinavir and two nucleoside analogs,[27] illustrating the substantial benefit of combining two NRTIs with a new class of antiretrovirals, protease inhibitors, namely indinavir. Later that year David Ho became an advocate of this "hit hard, hit early" approach with aggressive treatment with multiple antiretrovirals early in the course of the infection.[28] Later reviews in the late 90s and early 2000s noted that this approach of "hit hard, hit early" ran significant risks of increasing side effects and development of multidrug resistance, and this approach was largely abandoned. The only consensus was on treating patients with advanced immunosuppression (CD4 counts less than 350/μL).[29] Treatment with antiretrovirals was expensive at the time, ranging from $10,000 to $15,000 a year.[30]
The timing of when to start therapy has continued to be a core controversy within the medical community, though recent studies have led to more clarity. The NA-ACCORD[31] study observed patients who started antiretroviral therapy either at a CD4 count of less than 500 versus less than 350 and showed that patients who started ART at lower CD4 counts had a 69% increase in the risk of death.[31] In 2015 the START[32] and TEMPRANO[33] studies both showed that patients lived longer if they started antiretrovirals at the time of their diagnosis, rather than waiting for their CD4 counts to drop to a specified level.
Other arguments for starting therapy earlier are that people who start therapy later have been shown to have less recovery of their immune systems,[34] and higher CD4 counts are associated with less cancer.[35]
The European Medicines Agency (EMA) has recommended the granting of marketing authorizations for two new antiretroviral (ARV) medicines, rilpivirine (Rekambys) and cabotegravir (Vocabria), to be used together for the treatment of people with human immunodeficiency virus type 1 (HIV-1) infection.[36] The two medicines are the first ARVs that come in a long-acting injectable formulation.[36] This means that instead of daily pills, people receive intramuscular injections monthly or every two months.[36]
The combination of Rekambys and Vocabria injection is intended for maintenance treatment of adults who have undetectable HIV levels in the blood (viral load less than 50 copies/ml) with their current ARV treatment, and when the virus has not developed resistance to certain class of anti-HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (INIs).[36]
There are several concerns about antiretroviral regimens that should be addressed before initiating:
Response to therapy[edit]
Virologic response[edit]
Suppressing the viral load to undetectable levels (<50 copies per ml) is the primary goal of ART.[56] This should happen by 24 weeks after starting combination therapy.[83] Viral load monitoring is the most important predictor of response to treatment with ART.[84] Lack of viral load suppression on ART is termed virologic failure. Levels higher than 200 copies per ml is considered virologic failure, and should prompt further testing for potential viral resistance.[7]
Research has shown that people with an undetectable viral load are unable to transmit the virus through condomless sex with a partner of either gender. The 'Swiss Statement' of 2008 described the chance of transmission as 'very low' or 'negligible,'[85] but multiple studies have since shown that this mode of sexual transmission is impossible where the HIV-positive person has a consistently undetectable viral load. This discovery has led to the formation of the Prevention Access Campaign are their 'U=U' or 'Undetectable=Untransmittable' public information strategy,[86][87] an approach that has gained widespread support amongst HIV/AIDS-related medical, charitable, and research organisations.[42] The studies demonstrating that U=U is an effective strategy for preventing HIV transmission in serodiscordant couples so long as "the partner living with HIV [has] a durably suppressed viral load" include:[88] Opposites Attract,[89] PARTNER 1,[43] PARTNER 2,[90][91] (for male–male couples)[88] and HPTN052[92] (for heterosexual couples).[88] In these studies, couples where one partner was HIV-positive and one partner was HIV-negative were enrolled and regular HIV testing completed. In total from the four studies, 4097 couples were enrolled over four continents and 151,880 acts of condomless sex were reported, there were zero phylogenetically linked transmissions of HIV where the positive partner had an undetectable viral load.[93] Following this the U=U consensus statement advocating the use of 'zero risk' was signed by hundreds of individuals and organisations including the US CDC, British HIV Association and The Lancet medical journal.[42] The importance of the final results of the PARTNER 2 study were described by the medical director of the Terrence Higgins Trust as "impossible to overstate", while lead author Alison Rodger declared that the message that "undetectable viral load makes HIV untransmittable ... can help end the HIV pandemic by preventing HIV transmission."[94] The authors summarised their findings in The Lancet as follows:[90]
Salvage therapy[edit]
In patients who have persistently detectable viral loads while taking ART, tests can be done to investigate whether there is drug resistance. Most commonly a genotype is sequenced which can be compared with databases of other HIV viral genotypes and resistance profiles to predict response to therapy.[101] Resistance testing may improve virological outcomes in those who have treatment failures. However, there is lack of evidence of effectiveness of such testing in those who have not done any treatment before.[102]
If there is extensive resistance a phenotypic test of a patient's virus against a range of drug concentrations can be performed, but is expensive and can take several weeks, so genotypes are generally preferred.[7] Using information from a genotype or phenotype, a regimen of three drugs from at least two classes is constructed that will have the highest probability of suppressing the virus. If a regimen cannot be constructed from recommended first line agents it is termed salvage therapy, and when six or more drugs are needed it is termed mega-HAART.[103]
Structured treatment interruptions[edit]
Drug holidays (or "structured treatment interruptions") are intentional discontinuations of antiretroviral drug treatment. As mentioned above, randomized controlled studies of structured treatment interruptions have shown higher rates of opportunistic infections, cancers, heart attacks and death in patients who took drug holidays.[45][46][104] With the exception of post-exposure prophylaxis (PEP), treatment guidelines do not call for the interruption of drug therapy once it has been initiated.[7][44][83][104]
History[edit]
Several buyers clubs sprang up since 1986 to combat HIV. The drug zidovudine (AZT), a nucleoside reverse-transcriptase inhibitor (NRTI), was not effective on its own. It was approved by the US FDA in 1987.[124] The FDA bypassed stages of its review for safety and effectiveness in order to distribute this drug earlier.[125] Subsequently, several more NRTIs were developed but even in combination were unable to suppress the virus for long periods of time and patients still inevitably died.[126] To distinguish from this early antiretroviral therapy (ART), the term highly active antiretroviral therapy (HAART) was introduced. In 1996 two sequential publications in The New England Journal of Medicine by Hammer and colleagues[127] and Gulick and colleagues[27] illustrated the substantial benefit of combining two NRTIs with a new class of antiretrovirals, protease inhibitors, namely indinavir. This concept of three-drug therapy was quickly incorporated into clinical practice and rapidly showed impressive benefit with a 60% to 80% decline in rates of AIDS, death, and hospitalization.[2]
As HAART became widespread, fixed dose combinations were made available to ease the administration. Later, the term combination antiretroviral therapy (cART) gained favor with some physicians as a more accurate name, not conveying to patients any misguided idea of the nature of the therapy.[128] Today multidrug, highly effective regimens are long since the default in ART, which is why they are increasingly called simply ART instead of HAART or cART.[128] This retronymic process is linguistically comparable to the way that the words electronic computer and digital computer at first were needed to make useful distinctions in computing technology, but with the later irrelevance of the distinction, computer alone now covers their meaning. Thus as "all computers are digital now", so "all ART is combination ART now." However, the names HAART and cART, reinforced by thousands of earlier mentions in medical literature still being regularly cited, also remain in use.
Drug advertisements[edit]
Direct-to-consumer and other advertisements for HIV drugs in the past were criticized for their use of healthy, glamorous models rather than typical people with HIV/AIDS. Usually, these people will present with debilitating conditions or illnesses as a result of HIV/AIDS. In contrast, by featuring people in unrealistically strenuous activities, such as mountain climbing;[164] this proved to be offensive and insensitive to the suffering of people who are HIV positive. The US FDA reprimanded multiple pharmaceutical manufacturers for publishing such adverts in 2001, as the misleading advertisements harmed consumers by implying unproven benefits and failing to disclose important information about the drugs.[165] Overall, some drug companies chose not to present their drugs in a realistic way, which consequently harmed the general public's ideas, suggesting that HIV would not affect you as much as suggested. This led to people not wanting to get tested, for fear of being HIV positive, because at the time (in the 1980s and 1990s particularly), having contracted HIV was seen as a death sentence, as there was no known cure. An example of such a case is Freddie Mercury, who died in 1991, aged 45, of AIDS-related pneumonia.
Beyond medical management[edit]
The preamble to the World Health Organization's Constitution defines health as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity."[166] Those living with HIV today are met with other challenges that go beyond the singular goal of lowering their viral load. A 2009 meta-analysis studying the correlates of HIV-stigma found that individuals living with higher stigma burden were more likely to have poorer physical and mental health.[9] Insufficient social support and delayed diagnosis due to decreased frequency of HIV testing and knowledge of risk reduction were cited as some of the reasons.[9][167][8][168][169] People living with HIV (PLHIV) have lower health related quality of life (HRQoL) scores than do the general population.[168][167] The stigma of having HIV is often compounded with the stigma of identifying with the LGBTQ community or the stigma of being an injecting drug user (IDU) even though heterosexual sexual transmission accounts for 85% of all HIV-1 infections worldwide.[170][104] AIDS has been cited as the most heavily stigmatized medical condition among infectious diseases.[169] Part of the consequence of this stigma toward PLHIV is the belief that they are seen as responsible for their status and less deserving of treatment.[170][9]
A 2016 study sharing the WHO's definition of health critiques its 90-90-90 target goal, which is part of a larger strategy that aims to eliminate the AIDS epidemic as a public health threat by 2030, by arguing that it does not go far enough in ensuring the holistic health of PLHIV.[8] The study suggests that maintenance of HIV and AIDS should go beyond the suppression of viral load and the prevention of opportunistic infection. It proposes adding a 'fourth 90' addressing a new 'quality of life' target that would focus specifically on increasing the quality of life for those that are able to suppress their viral load to undetectable levels along with new metrics to track the progress toward that target.[8] This study serves as an example of the shifting paradigm in the dynamics of the health care system from being heavily 'disease-oriented' to more 'human-centered'. Though questions remain of what exactly a more 'human-centered' method of treatment looks like in practice, it generally aims to ask what kind of support, other than medical support, PLHIV need to cope with and eliminate HIV-related stigmas.[9][8] Campaigns and marketing aimed at educating the general public in order to reduce any misplaced fears of HIV contraction is one example.[9] Also encouraged is the capacity-building and guided development of PLHIV into more leadership roles with the goal of having a greater representation of this population in decision making positions.[9] Structural legal intervention has also been proposed, specifically referring to legal interventions to put in place protections against discrimination and improve access to employment opportunities.[9] On the side of the practitioner, greater competence for the experience of people living with HIV is encouraged alongside the promotion of an environment of nonjudgment and confidentiality.[9]
Psychosocial group interventions such as psychotherapy, relaxation, group support, and education may have some beneficial effects on depression in HIV positive people.[171]
Food insecurity[edit]
The successful treatment and management of HIV/AIDS is affected by a plethora of factors which ranges from successfully taking prescribed medications, preventing opportunistic infection, and food access etc. Food insecurity is a condition in which households lack access to adequate food because of limited money or other resources. Food insecurity is a global issue that has affected billions of people yearly, including those living in developed countries.
Food insecurity is a major public health disparity in the United States of America, which significantly affects minority groups, people living at or below the poverty line, and those who are living with one or more morbidity. As of December 31, 2017, there were approximately 126,742 people living with HIV/AIDS (PLWHA) in NYC, of whom 87.6% can be described as living with some level of poverty and food insecurity as reported by the NYC Department of Health on March 31, 2019.[172] Having access to a consistent food supply that is safe and healthy is an important part in the treatment and management of HIV/AIDS. PLWHA are also greatly affected by food inequities and food deserts which causes them to be food insecure. Food insecurity, which can cause malnutrition, can also negatively impact HIV treatment and recovery from opportunistic infections. Similarly, PLWHA require additional calories and nutritionally support that require foods free from contamination to prevent further immunocompromising. Food insecurity can further exacerbate the progression of HIV/AIDS and can prevent PLWHA from consistently following their prescribed regimen, which will lead to poor outcomes.
It is imperative that these food insecurity among PLWHA are addressed and rectified to reduce this health inequity. It is important to recognized that socioeconomic status, access to medical care, geographic location, public policy, race and ethnicity all play a pivotal role in the treatment and management of HIV/AIDS. The lack of sufficient and constant income does limit the options for food, treatment, and medications. The same can be inferred for those who are among the oppressed groups in society who are marginalized and may be less inclined or encouraged to seek care and assistance. Endeavors to address food insecurity should be included in HIV treatment programs and may help improve health outcomes if it also focuses on health equity among the diagnosed as much as it focuses on medications. Access to consistently safe and nutritious foods is one of the most important facets in ensuring PLWHA are being provided the best possible care. By altering the narratives for HIV treatment so that more support can be garnered to reduce food insecurity and other health disparities mortality rates will decrease for people living with HIV/AIDS.