Newborns Born To Mothers With Antiretroviral Drug
The optimal ARV regimen for newborns born to women with ARV drug-resistant virus is unknown. Although some studies have suggested that ARV drug-resistant virus may have decreased replicative capacity and transmissibility,47 perinatal transmission of multidrug-resistant virus does occur.4853 Whether resistant virus in the mother increases the antepartum/intrapartum risk of HIV acquisition by the infant also is unknown. A recently reported secondary analysis of data from the NICHD-HPTN 040/PACTG 1043 study demonstrated that the risk of perinatal transmission was not related to the presence of drug resistance mutations in mothers who had not received ARV drugs before the start of the study .53 Maraviroc was approved recently for infants 2 kg and may provide an additional treatment option for newborns of women carrying multidrug resistant HIV-1 that remains CCR5-trophic. However, the lack of data about MVC as prophylaxis or treatment in infants weighing < 10 kg and the risk of drug interactions will limit its role for routine use in neonates. The ARV regimen for newborns born to mothers with known or suspected drug resistance should be determined in consultation with a pediatric HIV specialist before delivery or through consultation via the National Perinatal HIV Hotline . Additionally, no evidence exists that shows that neonatal prophylaxis regimens customized based on presence of maternal drug resistance are more effective than standard neonatal prophylaxis regimens.
Alternatives To Antiretroviral Therapy
Whilst there are no alternatives to ART currently available, there is ongoing research into new and different HIV treatments.
One such approach being studied is , which involves modifying part of the bodys own genetic code in order to make CD4 cells resistant to HIV. Its hoped that gene therapy may be a functional HIV cure that could negate the need for antiretroviral therapy .
Another potential functional cure is bone marrow transplantation, however, there have only been two successful cases of this method to date .
Attempts to develop a vaccine against HIV are currently in progress. While ART allows people with HIV to maintain viral suppression, lifelong adherence to the treatment is essential. The only perceived way to eradicate the virus completely is to remove its ability to be transmitted in the first place .
How Does Antiretroviral Therapy Work
Antiretroviral therapy medication prevents the human immunodeficiency virus from multiplying, which reduces the viral load in the body. Having less HIV in the body allows the immune system to recover and produce more infection-fighting CD4 cells. Because the amount of HIV in the body is reduced, this also helps reduce the risk of HIV transmission.
There are several steps in the life cycle of HIV that form the basis for antiretroviral therapy.
HIV circulates in the bloodstream and binds to receptors on the surface of the CD4 immune cells, which leads to membrane fusion and internalization of the viral genetic material and enzymes necessary for replication of the virus.
Entry inhibitors include:
- Fusion inhibitor enfuvirtide
HIV uses reverse transcriptase to convert its genetic material into DNA, which results viral DNA migrating into the nucleus of the cell.
Nucleoside/nucleotide reverse transcriptase inhibitors include:
- Tenofovir disoproxil fumarate and tenofovir alafenamide
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The Impact Of Art On The Economic Outcomes Of People Living With Hiv/aids
1Infectious Diseases Institute Makerere University, Kampala, Uganda
2Rand Corporation, Santa Monica, CA 90401, USA
Background. Clinical benefits of ART are well documented, but less is known about its effects on economic outcomes such as work status and income in sub-Saharan Africa. Methods. Data were examined from 482 adult clients entering HIV care in Kampala, Uganda. Self-reported data on work status and income were assessed at baseline, months 6 and 12. Multivariate analysis examined the effects of ART over time, controlling for change in physical health functioning and baseline covariates. Results. Fewer ART patients worked at baseline compared to non-ART patients 48.8% of those not working at baseline were now working at month 6, and 50% at month 12, with similar improvement in both the ART and non-ART groups. However, multivariate analysis revealed that the ART group experienced greater improvement over time. Average weekly income did not differ between the groups at baseline nor change significantly over time, among those who were working being male gender and having any secondary education were predictive of higher income. . ART was associated with greater improvement in work status, even after controlling for change in physical health functioning, suggesting other factors associated with ART may influence work.
2.2.1. Work Status
2.2.2. Weekly Income Level
2.2.5. Physical Health
What Is Antiretroviral Therapy
Antiretroviral therapy refers to combination drug therapy used to treat human immunodeficiency virus . Antiretroviral drug therapy frequently combines three or more drugs from more than one class to help prevent drug resistance.
Antiretroviral therapy does not cure HIV, but it helps patients live longer and also reduces the risk of transmitting the virus to others. People who are diagnosed with HIV should start taking HIV medications right away.
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Is It Hard To Take These Drugs
The HIV medicines that currently are recommended are usually very simple and easy to take. Several drug combinations are available that package 3 separate medicines into only 1 pill, taken once a day, with minimal side effects.
For the great majority of people, HIV medicines are tolerable and effective, and let people with HIV live long and healthy lives. For some people, the drugs may be difficult to take every day, and for a small number, they cause serious side effects or don’t work well.
Once patients are on medications, they must work with their health care providers to find solutions for side effects and monitor how well the drugs are working.
The good news is that there are many excellent HIV medicines. Finding the right combination of medicines for each person is usually possible–a combination that controls the virus but does not cause side effects.
Choosing The Anchor Drug In Regimen
The choice of the third drug, commonly referred to as the anchor drug, to combine with an NRTI backbone for an initial antiretroviral regimen depends on clinical, pharmacologic, and patient-level factors. In the Adult and Adolescent ARV Guidelines, the Recommended Initial Regimens for Most People with HIV utilize the INSTI bictegravir or dolutegravir as the anchor drug the recommendation to use these two INSTIs as the anchor drug is based on high efficacy, high genetic barrier to resistance, low adverse effect profile, and minimal drug interactions. In previous years, the Adult and Adolescent ARV Guidelines included the INSTI elvitegravir, raltegravir, protease inhibitors, and NNRTIs as the anchor drug in the recommended regimen category, but certain limitations, such as poor tolerability, restrictions for use based on CD4 cell count and/or HIV RNA level, and lower genetic barrier to resistance have relegated these anchor drugs to the alternative regimen category.
Choice of INSTI
Choice of PI
Choice of NNRTI
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Data For Clinical Benefit Of Antiretroviral Therapy
The Adult and Adolescent ARV Guidelines recommendation to initiate antiretroviral therapy in all persons living with HIV to reduce morbidity and mortality is based on multiple cohort studies and clinical trials, as outlined below, that have shown a clear benefit of starting antiretroviral therapy earlier in the course of HIV disease progression.
How Can I Tell If My Treatment Is Working
Regular blood tests will show how well your treatment is working. The main blood test used to monitor how your body is responding to treatment measures the viral load .
The aim of HIV treatment is to lower your viral load and then to keep it as low as possible. When your viral load is very low, it is not possible for tests to measure it. This is a really good result, your viral load is called undetectable. You still have HIV, but it is being kept under control by the HIV treatment. Not only should you feel healthy, but if your viral load is undetectable, you cannot transmit HIV.
WHO recommends that you have a viral load test at 6 and 12 months after you start taking treatment, and then once every year. If treatment is begun early enough and followed correctly, your viral load can become undetectable within 6 months.
The other main blood test is a CD4 count, which shows the strength of your immune system. CD4 cells, an important part of your immune system, are attacked by the HIV virus. When you start taking treatment the numbers of CD4 cells you have will go up and if you were feeling ill because of HIV, you should start to feel better.
In some countries, viral load testing is not available. If this is the case where you are, your healthcare professional will monitor your health and your CD4 count in other ways.
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Barriers To Antiretroviral Therapy
HIV has a rapid rate of genomic evolution due to several factors:
- Rapid rate of viral production
- Rapid turnover of productively infected cells
- The reverse transcriptase enzyme being prone to errors.
This rapid genomic evolution allows new strains and mutations of HIV to arise, some of which are resistant to antiretroviral therapy .
According to the World Health Organization , up to 26% of people starting antiretroviral therapy are infected by an HIV strain that is resistant to first-line medicines.
Another identified issue is that in some cases, HIV viral load is detectable in semen despite being undetectable in the blood due to long-term ART. This suggests the presence of a persistent HIV reservoir in the male genital tract .
As with any treatment regimen, there are also patient-related factors that may increase the risk of adverse drug reactions to ART. These include:
- Other medicines being taken
- Comorbidities including underlying liver disease, viral hepatitis infection, liver steatosis and renal dysfunction
- Psychiatric disorders
- Genetic predisposition to hypersensitivity to certain antiretroviral medicines
- Age .
Compliance with treatment is essential and requires deep understanding and cooperation from patients and their family members. Consistent counselling and follow-ups are crucial in ensuring adherence.
What Barriers Do Patients Face In Adhering To Art
Barriers to ART adherence may arise from a patients personal or cultural beliefs, cognitive abilities, or health status, including comorbidities. 3,4,5 A patients capacity for treatment competence or regimen-specific barriers also may impact adherence, as well as psychosocial or structural issues such as poor mental health, drug use, or even lack of housing or health insurance. 3,4,5
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What Hiv Medicines Are Included In An Hiv Regimen
There are many HIV medicines available for HIV regimens. The HIV medicines are grouped into seven drug classes according to how they fight HIV.
The choice of an HIV regimen depends on a person’s individual needs. When choosing an HIV regimen, people with HIV and their health care providers consider many factors, including possible side effects of HIV medicines and potential drug interactions.
Randomized Controlled Trials Of Early Vs Deferred Antiretroviral Therapy
Two large randomized controlled trials, START and TEMPRANO, provide the evidence for the Panels recommendation to initiate ART in all patients regardless of CD4 count . The results of these two studies are summarized below.
START was a large, multi-national, randomized controlled clinical trial designed to evaluate the role of early ART initiation in asymptomatic patients with HIV in reducing a composite clinical endpoint of AIDS-defining illnesses, serious non-AIDS events, or death. The study began at a time when initiating ART was not recommended until an individuals CD4 count fell below 350 cells/mm3. In this study, ART-naive adults with CD4 counts > 500 cells/mm3 were randomized to initiate ART at randomization or to wait to initiate ART until their CD4 counts declined to < 350 cells/mm3 or until they developed a clinical indication for therapy .
More than 2,000 participants enrolled in the trial, with a median follow-up of 30 months. Among the 849 participants who had baseline CD4 counts > 500 cells/mm3, 68 primary outcome events were reported in 61 patients. The risk of primary events was lower among those who were randomized to start ART early than among those in the deferred arm, with an HR of 0.56 in favor of early ART . On the basis of these results, the study team concluded that early ART initiation is beneficial in reducing the rate of these clinical events.13
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Newborns Of Mothers Who Receive An Hiv Diagnosis While Breastfeeding
Women with suspected HIV should discontinue breastfeeding immediately until HIV is ruled out. Pumping and temporarily discarding or freezing breast milk can be recommended to mothers who are suspected of having HIV but whose HIV serostatus is not yet confirmed and who want to continue to breastfeed. If HIV is ruled out, breastfeeding can resume. Breastfeeding is not recommended for women with confirmed HIV in the United States, including those receiving ART .54
The risk of HIV acquisition associated with breastfeeding depends on multiple newborn and maternal factors, including maternal viral load and CD4 T lymphocyte cell count.55 Newborns of women who develop acute HIV while breastfeeding are at greater risk of acquiring HIV than those whose mothers have chronic HIV infection56 because acute HIV infection is accompanied by a rapid increase in viral load and a corresponding decrease in CD4 count.57
Other than discontinuing breastfeeding, optimal strategies for managing a newborn who was breastfed by a mother with HIV have yet to be defined. Some Panel members would consider the use of postexposure prophylaxis in newborns for 4 to 6 weeks after cessation of breastfeeding. Postexposure prophylaxis, however, is less likely to be effective in this circumstance than with other nonoccupational exposures because the exposure to breast milk is likely to have occurred over a prolonged period rather than during a single exposure to the virus.58
Immediate Antiretroviral Therapy Initiation On The Day Of Hiv Diagnosis
Since individuals may fail to engage in care between the initial HIV diagnosis and the time ART is prescribed, some groups have proposed rapid ART initiation on the same day of HIV diagnosis as a strategy to increase ART uptake and engagement in care and to accelerate the time to ART-mediated viral suppression. Rapid ART initiation also has the potential to reduce the time during which people with newly diagnosed HIV can transmit HIV. The rapid ART initiation strategy is supported by randomized controlled trials that were performed in resource-limited settings outside of the United States27-29 and observational trials in the United States that included both immediate initiation of ART 30-32 and rapid ART initiation .32,33 The results from some of these studies are discussed below.
There are many differences between health care in southern Africa and Haiti and in the United Statesincluding differences in the health care systems, structural barriers to engagement in care, underlying HIV and tuberculosis epidemics, and ART regimens usedthat limit the generalizability of the findings of the results from the studies described above. These studies, however, suggest that same-day initiation of ART is feasible and could potentially improve clinical outcomes.
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Use Of Art To Reduce The Risk Of Hiv Transmission
The proposal that ART be used to reduce the risk that an HIV-infected individual will transmit the virus is based on successful use of these agents to prevent perinatal transmission of HIV type 1 , on the biological and epidemiologic aspects of heterosexual transmission of HIV, and on the pharmacologic properties of ART.
However, mother-to-child transmission and sexual transmission are not analogous biological events, and the exact mechanism by which ART prevents mother-to-child transmission is not known. Some studies have documented mother-to-child transmission of HIV even when the mother’s HIV RNA level was undetectable. In addition, more-complete protection from HIV is observed when the neonate also receives ART .
Deductive reasoning suggests that sexual transmission should also be strongly related to the concentration of virus present in genital fluid, because this represents the infectious inoculum. In some investigations, HIV RNA concentrations in blood can be correlated with HIV RNA concentrations in genital fluid , and the correlation coefficient increases dramatically in subjects receiving ART . However, local replication of HIV is possible, particularly in the presence of inflammation . Chakraborty et al. have developed a model that predicts the probability of transmission of HIV from men to women as a function of HIV levels in seminal plasma.
Optimizing Adherence Antiretroviral Therapy Access And Care Engagement
The key to successfully maintaining viral suppression is continuous access to ART and adherence to the prescribed regimen. Lack of adherence or intermittent access to ART can result in treatment failure and the emergence of drug resistance mutations that may compromise future treatment options. While optimizing adherence and linkage to care and ensuring continuous access are critical regardless of the timing of ART initiation, the evidence thus far indicates that drug resistance occurs more frequently in individuals who initiate therapy later in the course of infection than in those who initiate ART earlier.48 It is important to discuss strategies to optimize adherence, care engagement, and ART access with all patients.
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What If I Have Another Illness Or A Co
You may have a co-infection or another illness such as cardiovascular disease, HIV-related cancer, chronic kidney disease or HIV-associated neurocognitive impairment.
In these situations your doctor may need to tailor your antiretroviral treatment or treat your other condition before starting your HIV treatment. This will be explained to you by the clinicians looking after you.
Hiv Entry And Entry Inhibitors
The initial step in the HIV life cycle involves a complex interaction between HIV envelope spikes and host surface proteins. The HIV envelope consists of two structural components: surface envelope glycoprotein and transmembrane envelope glycoprotein . The surface of HIV is studded with approximately 14 envelope spikes, with each spike consisting of a trimer of three gp120 and gp41 subunits . Both gp120 and gp41 play an essential role in HIV entry into the host cell.
- gp120: The gp120 subunit is the component of the envelope that interacts with the host receptors and coreceptors these interactions involve the gp120 CD4 binding site on the outermost surface of gp120 and the more internal variable 3 region of gp120. The gp120 V3 region plays a major role in determining the coreceptor tropism of HIV.
- gp41: The gp41 subunit consists of three domains: ectodomain , the transmembrane domain , and the cytoplasmic tail . The gp41 ectodomain has several functional components that include the N-terminal hydrophobic region and the N-terminal heptad repeat region 1 and the heptad repeat region 2 . Prior to cell binding, the HIV gp41 exist in a conformation in which the gp41 is folded back on itself in an energy loaded state.
HIV Entry Inhibitors
The FDA-approved HIV entry inhibitors includes three subclasses: CD4 postattachment inhibitor, CCR5 coreceptor antagonists, and fusion inhibitors each one of these subclasses of entry inhibitors has one FDA-approved drug.
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