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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine, even though the effectiveness of most of these therapies has not been established. There is not enough evidence to support the use of herbal medicines. There is insufficient evidence to recommend or support the use of medical cannabis to try to increase appetite or weight gain.
There is currently no cure or effective HIV vaccine. Treatment consists of highly active antiretroviral therapy (HAART) which slows progression of the disease. As of 2010 more than 6.6 million people were taking them in low and middle income countries. Treatment also includes preventive and active treatment of opportunistic infections.
It is currently recommended that HIV-infected individuals with TB receive combined treatment for both diseases, irrespective of CD4+ cell count. ART (Anti Retroviral Therapy) along with ATT (Anti Tuberculosis Treatment) is the only available treatment in present time. Though the timing of starting ART is the debatable question due to the risk of immune reconstitution inflammatory syndrome (IRIS). The advantages of early ART include reduction in early mortality, reduction in relapses, preventing drug resistance to ATT and reduction in occurrence of HIV-associated infections other than TB. The disadvantages include cumulative toxicity of ART and ATT, drug interactions leading to inflammatory reactions are the limiting factors for choosing the combination of ATT and ART.
A systematic review investigated the optimal timing of starting antiretroviral therapy in adults with newly diagnosed pulmonary tuberculosis. The review authors included eight trials, that were generally well-conducted, with over 4500 patients in total. The early provision of antiretroviral therapy in HIV-infected adults with newly diagnosed tuberculosis improved survival in patients who had a low CD4 count (less than 0.050 x 109 cells/L). However, such therapy doubled the risk for IRIS. Regarding patients with higher CD4 counts (more than 0.050 x 109 cells/L), the evidence is not sufficient to make a conclusion about benefits or risks of early antiretroviral therapy.
In the case of rape, the person can be treated prophylacticly with antibiotics.
An option for treating partners of patients (index cases) diagnosed with chlamydia or gonorrhea is patient-delivered partner therapy, which is the clinical practice of treating the sex partners of index cases by providing prescriptions or medications to the patient to take to his/her partner without the health care provider first examining the partner.
When HIV-negative children take isoniazid after they have been exposed to tuberculosis, their risk to contract tuberculosis is reduced. A Cochrane review investigated whether giving isoniazid to HIV-positive children can help to prevent this vulnerable group from getting tuberculosis. They included three trials conducted in South Africa and Botswana and found that isoniazid given to all children diagnosed with HIV may reduce the risk of active tuberculosis and death in children who are not on antiretroviral treatment. For children taking antiretroviral medication, no clear benefit was detected.
The goal of antiretroviral use during pregnancy is to reduce the risk of transmission of HIV from mother to child. It is important to choose medications that are safe for the mother and the fetus and which are effective at decreasing the total viral load. Some studies have shown an increase in stillbirths, preterm delivery, and delayed fetal growth in women using high doses of antiretroviral drugs during pregnancy. However, the overall benefits of ART are believed to outweigh the risks and all women are encouraged to use ART for the duration of their pregnancy.
Due to physiological changes in the body during pregnancy, it may be necessary to alter the dosing of medications so that they remain effective. Generally, the dose or the frequency of dosing are increased to account for these changes.
The recommended ART regimen for HIV-positive pregnant women consists of drugs from 4 different classes of medications listed below. In the United States, the favored regimen is a three-drug regimen where the first two drugs are NRTIs and the third is either a protease inhibitor, an integrase inhibitor, or an NNRTI.
- Nucleoside reverse transcriptase inhibitors (NRTIs) are considered the "backbone" of ART and 2 medications are generally used in combination. Due to its known safety profile and extensive use in pregnant patients, zidovudine-lamivudine (ZDV/3TC) is the preferred choice as the NRTI backbone. Zidovudine may worsen anemia, so patients with anemia are advised to use an alternative agent. For women who are coinfected with Hepatitis B, tenofovir with either emtricitabine or lamivudine is the preferred NRTI backbone. NRTI use may cause lactic acidosis in some women, so it is important to monitor patients for this complication. Deaths from lactic acidosis and liver failure have been associated with the use of two NRTIs, stavudine and didanosine (Zerit and Videx, respectively); therefore, combinations involving these drugs should be avoided in pregnancy.
- Protease inhibitors (PIs) have been studied extensively in pregnancy and are therefore the preferred third drug in the regimen. Atazanavir-ritonavir and darunavir-ritonavir are two of the most common PIs used during pregnancy. There is conflicting data regarding their association with preterm births, so women who are at a high risk for premature delivery are advised not to use PIs. Some PIs have been associated with hyperglycemia but is unclear whether they add to the risk of developing gestational diabetes. Some PIs have been noted to cause hyperbilirubinemia and nausea, so these side effects should be monitored for closely.
- Integrase inhibitors (IIs) are generally the third drug in the regimen when a PI cannot be used. They rapidly reduce the viral load and for this reason, they are often used in women who are diagnosed with HIV late in the pregnancy. Raltegravir is the most common II used.
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs), the most popular being efavirenz and nevirapine, may be used during pregnancy. However, there are significant toxicities associated with their use, making them a less desirable option.
- Efavirenz (brand name Sustiva, and a component of the combination drug Atripla) is classified as a category D drug by the US Food and Drug Administration indicating there are risks associated with its use during pregnancy. In a study analyzing the use of the drug in pregnant women, 2.3% of births were associated with birth defects. However, a systematic review of the safety of efavirenz use in humans during the first trimester found no increase in birth defects among women using the drug. Given the uncertain potential for risk the U.S. DHHS recommends against using efavirenz in the first trimester of pregnancy or in women who may become pregnant. They instead recommend a protease inhibitor based regimen with lopinavir or atazanavir. However, to simplify regimens and provide a uniform recommendation for HIV-infected individuals during pregnancy, the WHO continues to recommend efavirenz as a first line agent for HIV positive women. Women using efavirenz prior to their pregnancy may continue with the drug as it is more dangerous to stop or change medications during pregnancy because this can result in improper control of the viral load.
- Nevirapine (trade name Viramune) increases the risk of very serious liver damage in women with CD4 counts greater than 250 cells/mm . It is generally avoided in pregnant women. Women taking nevirapine safely prior to pregnancy may continue with the medication because nevirapine-related liver damage has not been seen in women previously using the medication.
Exposure to antiretroviral treatments has led to the evolution of HIV in response to selection pressure that eliminates strains of HIV that do not express resistance mechanisms. Drug resistance occurs in all antiretroviral treatments if patients are non-adherent, meaning that they do not take their medication regimens as prescribed. Lack of adherence may result from unreliable access to the medication, due to prohibitive cost or inadequate supply.
Current medical and scientific opinion is mixed on the most effective treatment methods, but is focused on drug cocktails and the importance of first-line regimens . The World Health Organization advocates a public-health approach to HIV treatment in order to make treatment uniform and available to patients around the world. As of July 2017, the WHO is implementing the Global Action Plan on HIV drug resistance 2017-2021. It is a 5-year initiative intended to help countries around the world manage HIV drug resistance.
Among treatment methods, the World Health Organization acknowledges the importance of successful first-line treatments. First-line treatments are known to affect the virus’ future response to other treatments, making the effectiveness of first-line treatments an issue of vital importance. The most successful treatments are combinations of three drugs used simultaneously, as this greatly reduces the probability of the virus developing resistance.
The principles of treatment for MDR-TB and for XDR-TB are the same. Treatment requires extensive chemotherapy for up to two years. Second-line drugs are more toxic than the standard anti-TB regimen and can cause a range of serious side-effects including hepatitis, depression, hallucinations, and deafness. Patients are often hospitalized for long periods, in isolation. In addition, second-line drugs are extremely expensive compared with the cost of drugs for standard TB treatment.
XDR-TB is associated with a much higher mortality rate than MDR-TB, because of a reduced number of effective treatment options. Despite early fears that this strain of TB was untreatable, recent studies have shown that XDR-TB can be treated through the use of aggressive regimens. A study in the Tomsk oblast of Russia, reported that 14 out of 29 (48.3%) patients with XDR-TB successfully completed treatment. Nix-TB regimen, a combination pretomanid, bedaquiline, and linezolid, has shown promise in early clinical trials.
Successful outcomes depend on a number of factors including the extent of the drug resistance, the severity of the disease and whether the patient’s immune system is compromised. It also depends on access to laboratories that can provide early and accurate diagnosis so that effective treatment is provided as soon as possible. Effective treatment requires that all six classes of second-line drugs be available to clinicians who have special expertise in treating such cases.
Researchers had hoped that nonoxynol-9, a vaginal microbicide would help decrease STI risk. Trials, however, have found it ineffective and it may put women at a higher risk of HIV infection.
Treatment for both pregnant and non-pregnant women is usually with metronidazole, by mouth once. Caution should be used in pregnancy, especially in the first trimester. Sexual partners, even if they have no symptoms, should also be treated.
For 95-97% of cases, infection is resolved after one dose of metronidazole. Studies suggest that 4-5% of trichomonas cases are resistant to metronidazole, which may account for some “repeat” cases. Without treatment, trichomoniasis can persist for months to years in women, and is thought to improve without treatment in men. Women living with HIV infection have better cure rates if treated for 7 days rather than with one dose.
Topical treatments are less effective than oral antibiotics due to Skene's gland and other genitourinary structures acting as a reservoir.
According to current recommendations by the WHO, US CDC and U.S. Department of Health and Human Services (DHHS), all individuals with HIV should begin ART. The recommendation is stronger under the following conditions:
- CD4 count below 350 cells/mm
- High viral load (>100,000 copies/ml)
- Progression of HIV to AIDS
- Development of HIV-related infections and illnesses
- Pregnancy
Women are encouraged to begin treatment as soon as they are diagnosed with HIV. If they are diagnosed prior to pregnancy, they should continue with ART during the pregnancy. If the diagnosis of HIV is made during the pregnancy, ART should be initiated immediately.
Treatments of proven efficacy are currently limited mostly to herpes viruses and human immunodeficiency virus. The herpes virus is of two types: herpes type 1 (HSV-1, or oral herpes) and herpes type 2 (HSV-2, or genital herpes). Although there is no particular cure; there are treatments that can relieve the symptoms. Drugs like Famvir, Zovirax, and Valtrex are among the drugs used, but these medications can only decrease pain and shorten the healing time. They can also decrease the total number of outbreaks in the surrounding. Warm baths also may relive the pain of genital herpes.
Human Immunodeficiency Virus Infection (HIV) is treated by using a combination of medications to fight against the HIV infection in the body. This is called antiretroviral therapy (ART). ART is not a cure, but it can control the virus so that a person can live a longer, healthier life and reduce the risk of transmitting HIV to others around him. ART involves taking a combination of HIV medicines (called an HIV regimen) every day, exactly as prescribed by the doctor. These HIV medicines prevent HIV Virus from multiplying (making copies of itself in the body), which reduces the amount of HIV in the body. Having less HIV in the body gives the immune system a chance to recover and fight off infections and cancers. Even though there is still some HIV in the body, the immune system is strong enough to fight off infections and cancers. By reducing the amount of HIV in the body, HIV medicines also reduce the risk of transmitting the virus to others. ART is recommended for all people with HIV, regardless of how long they’ve had the virus or how healthy they are. If left untreated, HIV will attack the immune system and eventually progress to AIDS.
Countries aim to prevent XDR-TB by ensuring that the work of their national TB control programmes, and of all practitioners working with people with TB, is carried out according to the International Standards for TB Care. These emphasize providing proper diagnosis and treatment to all TB patients, including those with drug-resistant TB; assuring regular, timely supplies of all anti-TB drugs; proper management of anti-TB drugs and providing support to patients to maximize adherence to prescribed regimens; caring for XDR-TB cases in a centre with proper ventilation, and minimizing contact with other patients, particularly those with HIV, especially in the early stages before treatment has had a chance to reduce the infectiousness. Also an effective disease control infrastructure is necessary for the prevention of XDR tuberculosis. Increased funding for research, and strengthened laboratory facilities are much required. Immediate detection through drug susceptibility testing's are vital, when trying to stop the spread of XDR tuberculosis.
Some vertically transmitted infections, such as toxoplasmosis and syphilis, can be effectively treated with antibiotics if the mother is diagnosed early in her pregnancy. Many viral vertically transmitted infections have no effective treatment, but some, notably rubella and varicella-zoster, can be prevented by vaccinating the mother prior to pregnancy.
If the mother has active herpes simplex (as may be suggested by a pap test), delivery by Caesarean section can prevent the newborn from contact, and consequent infection, with this virus.
IgG antibody may play crucial role in prevention of intrauterine infections and extensive research is going on for developing IgG-based therapies for treatment and vaccination.
Treatment options in persons without HIV-infection have not been well studied. Intravenous Amphotericin B combined with flucytosine by mouth is recommended.
Persons living with AIDS often have a greater burden of disease and higher mortality (30-70% at 10-weeks), but recommended therapy is with amphotericin B and flucytosine. Where flucytosine is not available (many low and middle income countries), fluconazole should be used with amphotericin. Amphotericin-based induction therapy has much greater microbiologic activity than fluconazole monotherapy with 30% better survival at 10-weeks. Based on a systematic review of existing data, the most cost-effective induction treatment in resource-limited settings appears to be one week of amphotericin B coupled with high-dose fluconazole. After initial induction treatment as above, typical consolidation therapy is with oral fluconazole for at least 8 weeks used with secondary prophylaxis with fluconazole thereafter.
The decision on when to start treatment for HIV appears to be very different than other opportunistic infections. A large multi-site trial supports deferring ART for 4–6 weeks was overall preferable with 15% better 1-year survival than earlier ART initiation at 1–2 weeks after diagnosis. A Cochrane review also supports the delayed starting of treatment until cryptococcosis starts improving with antifungal treatment.
Evidence from a randomized controlled trials for screening pregnant women who do not have symptoms for infection with trichomoniasis and treating women who test positive for the infection have not consistently shown a reduced risk of preterm birth. Further studies are needed to verify this result and determine the best method of screening. In the US, screening of pregnant women without any symptoms is only recommended in those with HIV as trichomonas infection is associated with increased risk of transmitting HIV to the fetus.
Development of new therapies has been hindered by the lack of appropriate animal model systems for some important viruses and also because of the difficulty in conducting human clinical trials for diseases that are rare. Nonetheless, numerous innovative approaches to antiviral therapy are available including candidate thiazolide and purazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpes virus drugs include viral helicase-primase and terminase inhibitors. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses.
Usually, multidrug-resistant tuberculosis can be cured with long treatments of second-line drugs, but these are more expensive than first-line drugs and have more adverse effects. The treatment and prognosis of MDR-TB are much more akin to those for cancer than to those for infection. MDR-TB has a mortality rate of up to 80%, which depends on a number of factors, including
1. How many drugs the organism is resistant to (the fewer the better)
2. How many drugs the patient is given (patients treated with five or more drugs do better)
3. Whether an injectable drug is given or not (it should be given for the first three months at least)
4. The expertise and experience of the physician responsible
5. How co-operative the patient is with treatment (treatment is arduous and long, and requires persistence and determination on the part of the patient)
6. Whether the patient is HIV positive or not (HIV co-infection is associated with an increased mortality).
The majority of patients suffering from multi-drug-resistant tuberculosis do not receive treatment, as they are found in underdeveloped countries or in poverty. Denial of treatment remains a difficult human rights issue, as the high cost of second-line medications often precludes those who cannot afford therapy.
A study of cost-effective strategies for tuberculosis control supported three major policies. First, the treatment of smear-positive cases in DOTS programs must be the foundation of any tuberculosis control approach, and should be a basic practice for all control programs. Second, there is a powerful economic case for treating smear-negative and extra-pulmonary cases in DOTS programs along with treating smear-negative and extra-pulmonary cases in DOTS programs as a new WHO “STOP TB” approach and the second global plan for tuberculosis control. Last, but not least, the study shows that significant scaling up of all interventions is needed in the next 10 years if the millennium development goal and related goals for tuberculosis control are to be achieved. If the case detection rate can be improved, this will guarantee that people who gain access to treatment facilities are covered and that coverage is widely distributed to people who do not now have access.
In general, treatment courses are measured in months to years; MDR-TB may require surgery, and death rates remain high despite optimal treatment. However, good outcomes for patients are still possible.
The treatment of MDR-TB must be undertaken by physicians experienced in the treatment of MDR-TB. Mortality and morbidity in patients treated in non-specialist centers are significantly higher to those of patients treated in specialist centers. Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients without this information. When treating a patient with suspected MDR-TB, pending the result of laboratory sensitivity testing, the patient could be started on SHREZ (Streptomycin+ isonicotinyl Hydrazine+ Rifampicin+Ethambutol+ pyraZinamide) and moxifloxacin with cycloserine. There is evidence that previous therapy with a drug for more than a month is associated with diminished efficacy of that drug regardless of "in vitro" tests indicating susceptibility. Hence, a detailed knowledge of the treatment history of each patient is essential. In addition to the obvious risks (i.e., known exposure to a patient with MDR-TB), risk factors for MDR-TB include HIV infection, previous incarceration, failed TB treatment, failure to respond to standard TB treatment, and relapse following standard TB treatment.
A gene probe for "rpoB" is available in some countries. This serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). If the results of a gene probe ("rpoB") are known to be positive, then it is reasonable to omit RMP and to use SHEZ+MXF+cycloserine. The reason for maintaining the patient on INH is that INH is so potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective (even though isoniazid resistance so commonly occurs with rifampicin resistance).
When sensitivities are known and the isolate is confirmed as resistant to both INH and RMP, five drugs should be chosen in the following order (based on known sensitivities):
- an aminoglycoside (e.g., amikacin, kanamycin) or polypeptide antibiotic (e.g., capreomycin)
- pyrazinamide
- ethambutol
- a fluoroquinolone (e.g., moxifloxacin (ciprofloxacin) should no longer be used);
- rifabutin
- cycloserine
- a thioamide: prothionamide or ethionamide
- PAS
- a macrolide: e.g., clarithromycin
- linezolid
- high-dose INH (if low-level resistance)
- interferon-γ
- thioridazine
- Ampicillin
"Note:" Drugs placed nearer the top of the list are more effective and less toxic; drugs placed nearer the bottom of the list are less effective or more toxic, or more difficult to obtain.
In general, resistance to one drug within a class means resistance to all drugs within that class, but a notable exception is rifabutin: Rifampicin-resistance does not always mean rifabutin-resistance, and the laboratory should be asked to test for it. It is possible to use only one drug within each drug class. If it is difficult finding five drugs to treat then the clinician can request that high-level INH-resistance be looked for. If the strain has only low-level INH-resistance (resistance at 0.2 mg/l INH, but sensitive at 1.0 mg/l INH), then high dose INH can be used as part of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when adding PZA to a four-drug regimen, another drug must be chosen to make five. It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: If possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter). Ciprofloxacin should not be used in the treatment of tuberculosis if other fluoroquinolones are available.
There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that giving injectable drugs for five days a week (because there is no-one available to give the drug at weekends) does not seem to result in inferior results. Directly observed therapy helps to improve outcomes in MDR-TB and should be considered an integral part of the treatment of MDR-TB.
Response to treatment must be obtained by repeated sputum cultures (monthly if possible). Treatment for MDR-TB must be given for a minimum of 18 months and cannot be stopped until the patient has been culture-negative for a minimum of nine months. It is not unusual for patients with MDR-TB to be on treatment for two years or more.
Patients with MDR-TB should be isolated in negative-pressure rooms, if possible. Patients with MDR-TB should not be accommodated on the same ward as immunosuppressed patients (HIV-infected patients, or patients on immunosuppressive drugs). Careful monitoring of compliance with treatment is crucial to the management of MDR-TB (and some physicians insist on hospitalisation if only for this reason). Some physicians will insist that these patients remain isolated until their sputum is smear-negative, or even culture-negative (which may take many months, or even years). Keeping these patients in hospital for weeks (or months) on end may be a practical or physical impossibility, and the final decision depends on the clinical judgement of the physician treating that patient. The attending physician should make full use of therapeutic drug monitoring (in particular, of the aminoglycosides) both to monitor compliance and to avoid toxic effects.
Some supplements may be useful as adjuncts in the treatment of tuberculosis, but, for the purposes of counting drugs for MDR-TB, they count as zero (if four drugs are already in the regimen, it may be beneficial to add arginine or vitamin D or both, but another drug will be needed to make five).
- arginine (peanuts are a good source)
- vitamin D
- Dzherelo
- V5 Immunitor
The drugs listed below have been used in desperation, and it is uncertain as to whether they are effective at all. They are used when it is not possible to find five drugs from the list above.
- imipenem
- co-amoxiclav
- clofazimine
- prochlorperazine
- metronidazole
On December 28, 2012 the U.S. Food and Drug Administration (FDA) approved bedaquiline (marketed as Sirturo by Johnson & Johnson) to treat multi-drug resistant tuberculosis, the first new treatment in 40 years. Sirturo is to be used in a combination therapy for patients who have failed standard treatment and have no other options. Sirturo is an adenosine triphosphate synthase (ATP synthase) inhibitor.
The following drugs are experimental compounds that are not commercially available, but may be obtained from the manufacturer as part of a clinical trial or on a compassionate basis. Their efficacy and safety are unknown:
- pretomanid (manufactured by Novartis, developed in partnership with TB Alliance)
- delamanid
In cases of extremely resistant disease, surgery to remove infection portions of the lung is, in general, the final option. The center with the largest experience in this is the National Jewish Medical and Research Center in Denver, Colorado. In 17 years of experience, they have performed 180 operations; of these, 98 were lobectomies and 82 were pneumonectomies. There is a 3.3% operative mortality, with an additional 6.8% dying following the operation; 12% experienced significant morbidity (in particular, extreme breathlessness). Of 91 patients who were culture-positive before surgery, only 4 were culture-positive after surgery.
The resurgence of tuberculosis in the United States, the advent of HIV-related tuberculosis, and the development of strains of TB resistant to the first-line therapies developed in recent decades—serve to reinforce the thesis that Mycobacterium tuberculosis, the causative organism, makes its own preferential option for the poor. The simple truth is that almost all tuberculosis deaths result from a lack of access to existing effective therapy.
Penicillin is used to treat neurosyphilis; however, early diagnosis and treatment is critical. Two examples of penicillin therapies include:
- Aqueous penicillin G 3–4 million units every four hours for 10 to 14 days.
- One daily intramuscular injection and oral probenecid four times daily, both for 10 to 14 days.
Follow-up blood tests are generally performed at 3, 6, 12, 24, and 36 months to make sure the infection is gone. Lumbar punctures for CSF fluid analysis are generally performed every 6 months.
Neurosyphilis was almost at the point being unheard of in the United States after penicillin therapy was introduced. However, concurrent infection of "T. pallidum" with human immunodeficiency virus (HIV) has been found to affect the course of syphilis. Syphilis can lie dormant for 10 to 20 years before progressing to neurosyphilis, but HIV may accelerate the rate of the progress. Also, infection with HIV has been found to cause penicillin therapy to fail more often. Therefore, neurosyphilis has once again been prevalent in societies with high HIV rates and limited access to penicillin. Blood testing for syphilis was once required in order to obtain a marriage license in most U.S. states, but that requirement has been discontinued by all 50 states over recent years, also contributing to the spread of the disease.
It is unknown what aspects of the natural immune response to HIV may protect someone from superinfection, but it has been shown that cytotoxic lymphocyte responses do not seem to be protective. In addition, it has been demonstrated that superinfection can occur in individuals that demonstrate a robust anti-HIV antibody response. The anti-HIV antibody response broadens and strengthens in individuals post-superinfection.
Taken with the finding that super-infection is common and occurs within and between HIV subtypes it has been suggested that the immune response elicited by primary infection may confer limited protection and raises concerns that HIV-vaccine strategies designed to replicate the natural anti-HIV immune response may have limited effectiveness in preventing new infections. However at the same time, HIV-infected individuals at high risk for super-infection who do not become superinfected may also provide a very interesting avenue for new vaccine research.
Fumagillin has been used in the treatment.
Another agent used is albendazole.
Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.
Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.
Each type of vertically transmitted infection has a different prognosis. The stage of the pregnancy at the time of infection also can change the effect on the newborn.
People with AIDS are given macrolide antibiotics such as azithromycin for prophylactic treatment.
People with HIV infection and less than 50 CD4+ T-lymphocytes/uL should be administered prophylaxis against MAC. Prophylaxis should be continued for the patient's lifetime unless multiple drug therapy for MAC becomes necessary because of the development of MAC disease.
Clinicians must weigh the potential benefits of MAC prophylaxis against the potential for toxicities and drug interactions, the cost, the potential to produce resistance in a community with a high rate of tuberculosis, and the possibility that the addition of another drug to the medical regimen may adversely affect patients' compliance with treatment. Because of these concerns, therefore, in some situations rifabutin prophylaxis should not be administered.
Before prophylaxis is administered, patients should be assessed to ensure that they do not have active disease due to MAC, M. tuberculosis, or any other mycobacterial species. This assessment may include a chest radiograph and tuberculin skin test.
Rifabutin, by mouth daily, is recommended for the people's lifetime unless disseminated MAC develops, which would then require multiple drug therapy. Although other drugs, such as azithromycin and clarithromycin, have laboratory and clinical activity against MAC, none has been shown in a prospective, controlled trial to be effective and safe for prophylaxis. Thus, in the absence of data, no other regimen can be recommended at this time.The 300-mg dose of rifabutin has been well tolerated. Adverse effects included neutropenia, thrombocytopenia, rash, and gastrointestinal disturbances.
Many people living with HIV in low and middle income countries who need antiretroviral therapy are unable to access or remain in care. This is often because of the time and cost required to travel to health centres as well as an inadequate number of trained staff such as medical doctors and specialists to provide treatment. One approach to improve access to HIV care is to provide antiretroviral therapy close to people’s homes. A systematic review found that when antiretroviral treatment was initiated at the hospital but followed up at a health centre closer to home, fewer patients died or were lost to follow up. The research also did not detect a difference in the numbers of patients who died or were lost to follow up when they received maintenance treatment in the community rather than in a health centre or hospital.