More than 90% of cases of acute HIV infection go unrecognized.
In 2016 about 80% of new HIV cases stemmed from people who didn’t know they had HIV or were not receiving treatment.
In 2021 the number of new infections worldwide exceeds 5000 per day.
Presently, an estimated one in seven persons with HIV in the US is unaware of the infection.
A minimum of 300,000 Americans are estimated to be unaware of having HIV.
Presently (in 2018) about 86% of patients living with HIV have received that diagnosis.
Most of the 75.7 million people with HIV infection worldwide are in sub-Saharan Africa, were subtype C of HIV type 1 is prevalent.
It is estimated that more than 1.1 million people in the US are living with HIV infection.
Without treatment for HIV infection it causes AIDS and AIDS-defining cancers: non-Hodgkin’s lymphoma, Kaposi’s sarcoma, and cervical cancer.
25% of all new cases occur in white persons.
In acute infection the mucosa is the dominant site of infection.
Acute infection contributes disproportionately to HIV transmission.
Viral load often peaks at greater than 10 million copies per mL. contribute to this highly infectious phase.
Identifying patients with acute HIV infection is critical to preventing further disease transmission, as diagnosis can lead to preventive interventions.
Individuals with HIV who receive anti-retroviral therapy and have achieved and maintained an undetectable viral load can not sexually transmit virus to others.
Acute HIV infection is characterized as the interval between the appearance of HIV
RNA and detection of HIV specific antibodies.
Acute HIV infection is diagnosed with assay that detect either HIV RNA or the p24 antigen, an HIV core protein, which are both detectable early after HIV infection and before an anybody response develops.
Approximately 1.1 million people in the US are infected with HIV.
At the present rate one in two black men who have sex with men in the United States will contract HIV during their lifetime.
80% of adults are infected through exposure of the mucosal surfaces to the virus, while 20% are infected by cutaneous or intravenous inoculations.
An estimated 7500 incident HIV infections occur each day worldwide.
HIV infections have decreased by an estimated 33% since 2001 but remains high with approximately 2.2 million new infections in 2012.
In the US approximately 35,000 infections occur each year, and the number is unchanged since the 1990s.
As of 2011 more than 34 million adults and children living with HIV.
Death from AIDS-related causes peaked in 1995 in the United States and globally in 2005.
Leading cause of death in patients with HIV is tuberculosis.
People living with HIV have higher risk of cardiovascular disease including myocardial infarction, heart failure, stroke, pulmonary hypertension, and sudden cardiac death then those without HIV.
Worldwide an approximately 1000 people with HIV virus infection die from tuberculosis each day.
HIV patients have a life expectancy near those of I infected counterparts, and infected patients are about as likely to die from HIV independent comorbidities as from HIV/acquired immunodeficiency syndrome.
Women with HIV have decreased fertility, as they are more likely to be infected with other sexually transmitted diseases, placing them at higher risk
Males with HIV appear to have decreased semen volume and sperm motility, which decreases their fertility.
Less than 0.5% of patients have remained clinically well without antiretroviral therapy after as many as 20 years of infection.
Estimated 1.2 million people in the US are infected with HIV, and approximately 250,0000 remain undiagnosed and approximately 37,000 new cases are diagnosed each year.
Estimated 34 million people infected worldwide.
In the US an estimated 48,100 new cases occurred in 2009: of these 27% were in heterosexual men and women who not inject drugs, and 64% were in men having sex with men, including 3% of those who inject drugs.
Responsible for deaths of 30 million people.
The natural course of HIV infection is associated with three stages: the acute infectious stage characterized by viremia, rapid decrease in CD4 positive T-cell count and development of influenza like symptoms, an asymptomatic stage with the continuous and moderate declining T-cell counts and AIDS, Acquired Immune Deficiency Syndrome with opportunistic diseases developing due to a a dysfunction of the immune system.
Acute infection is rarely recognized and is associated with a high probability of secondary HIV transmission because of the magnitude of the viremia and shedding of the virus from the genitalia.
After the initial exposure to the virus, replication of the virus occurs in the mucosa, submucosa and draining lymphoreticular tissues and the virus can not be detected in the plasma-this phase is called the eclipse phase, and generally lasts 7-21 days.
The virus can be detected when the HIV-1 RNA reaches a concentration of 1-5 copies per milimeter in plasma by nucleic acid amplification techniques.
The virus can be detected when the HIV-1 RNA reaches a concentration of 50 copies per millimeter by quantitative assay.
HIV infection is characterized by rapid and profound decrease in peripheral blood CD4 + T cells: this is followed by spontaneous but transient recovery in the cell counts, and subsequently there is a progressive decline in CD4 positive counts.
During the acute infection viral load peaks in the blood and genital secretions and makes the individual highly infectious.
Concentration of HIV in blood and seminal plasma correlates with the probability of transmission of HIV to a sexual partner: Reducing levels of HIV with ART decreases the probability of transmission.
Acute human immunodeficiency virus infection is the stage of the disease in which viral replication and shedding occurs before detectable antibody appears.
Acute HIV infection, 5-15% have genital ulcers.
During acute human immunodeficiency virus infection the viral load peaks in the blood and genital secretions, making the individual highly infectious.
Up to 50% of new HIV infections are acquired by the onward transmission from individuals with acute HIV infection.
Three rapid is techniques are regularly used: immunoconcentration, immunochromatohraphy, and particle agglutinatioin.
Rapid testing, generally, use HIV-1 antigens, typically located in the Gag and Env regions of HIV, that are fixed or coated on a test strip-a positive will be as a result of HIV antibodies in the specimen.
Conventional HIV antibody screening tests are third-generation immunoassays testing for HIV antibodies are able to identify infections earlier than previous assays.
Testing is also recommended after the diagnosis of incident sexually transmitted infections and during pregnancy.
The natural immune response to HIV infection is inadequate to control infection.
Neutralizing bodies generated during HIV infection are mostly directed towards exposed highly variable portions of the HIV envelope protein on the viral particle.
Antibodies generated early in HIV infection are directed at the intersecting viral strain, which rapidly evolves to escape recognition.
The p24 antigen, a major core HIV protein, can be detected earlier than HIV antibody.
Acute infection can be identified by nucleic acid amplification testing (NAAT) and can detect HIV infection 45 days earlier than first generation IgG sensitive indirect enzyme immunoassays, 32 days sooner than second-generation EIAs, 11 days sooner than third-generation EIAs and six days sooner than fourth-generation EIAs (Feibig EW).
Acute HIV infection associated with a negative test for HIV antibodies on EIA, a negative or indeterminate test for HIV on Western blot analysis, and detection of HIV-1 RNA in plasma.
Acute HIV infection associated with an acute retroviral syndrome occurring 2-3 weeks after infection, usually coinciding with onset of viremia, and is accompanied by nonspecific symptoms, including fatigue, pharyngitis, weight loss, headache and myalgia.
A transient decline in CD4+ lymphocyte count is characteristic od acute HIV infections.
HIV primarily infects activated CD4 T cells integrating its genetic material into the hosts cells DNA and co-opts the cell’s machinery to make new virus particles that move out of the cell to infect others cells.
Many infected CD4 T cells die because of the cytopathic effects of the virus or because immune system’s CD8 killer T cells eliminate the infected cells.
Micronutrient deficiencies are prevalent before the development of symptoms of HIV disease and are associated with accelerated HIV disease progression.
Micronutrient supplementation improves markers of HIV disease progression such as CD4 cell count, HIV viral load and mortality.
Vitamin D, vitamin C and vitamin E, and the trace element selenium are essential nutrients for maintaining a response of immune system.
For each new recipient of treatment, worldwide, another 10 persons will become infected.
The WHO reports the rate of sudden cardiac death among HIV positive persons is 4.5 times general population.
About 30-40 infants become infected with HIV through perinatal transmission each year in the U.S.
Approximately 43% of patients with HIV present as late testers, meaning they present at a time when their CD4 Tone lymphocyte cell counts or less than 200 cells per microL.
Estimated 56,000 new cases in U.S. during 2006, with an incidence of 22.8 cases per 100,000 population.
Incidence peaked in the U.S. in the mid 1980s to approximately 130,000 new infections annually and reached low levels of about 50,000 cases in the early 1990s.
It is estimated that the number of persons with HIV/AIDS 50 years and older increased by 77% from 2001 to 2005.
Number of persons aged 50 years or older accounted for 15% of newly diagnosed cases in 2005.
Between 180,000 and 280,000 infected persons are unaware of their infected status.
About 21% of HIV infected persons in the US are unaware of their serostatus.
HIV patients have an early onset of cardiovascular disease .
HIV infected patients have 50-100 percent greater cardiovascular risk.
Overall prevalence of HIV cannot be measured directly because a large proportion of infected persons have not been diagnosed or reported to surveillance programs.
In 2009, 57% of newly diagnosed cases were transmitted by male to male sexual contact, 31% by heterosexual contact, and 9% by drug injection, and 3% by male to male sexual contact and injection drug use.
With the advent of highly active antiretroviral therapies that cause delay in the progression of HIV to AIDS and of deaths from AIDS methods to estimating prevalence of HIV based on the number of cases of reported AIDS is no longer reliable.
Life expectancy and age specific death rates in some successfully treated subgroups of HIV-infected patients has been estimated to approach those of the uninfected general population (Bhaskaran K et al, Lewden C et al).
Patients with HIV have a shorter lifespan then uninfected counterparts and greater than expected risk of cardiovascular disease, in part due to associated traditional risk factors such a cigarette smoking, the effects of antiretroviral therapy on lipids, insulin resistance, and body composition.
HIV subtype C is associated with a more prolonged early viremia and a higher setpoint than other HIV subtypes, with more adverse health consequences.
It is suspected that chronic inflammation and immune activation are associated with increased risk of HIV-associated cardiovascular disease.
Immunologic modulations may play a role in atherosclerosis in patients with HIV.
Patients with HIV have a high prevalence of noncalcified coronary atherosclerotic lesions that are increased with markers of macrophage activation.
There is a significant infiltration of activated monocytes and macrophages in the endothelium and contributes to the development of atherosclerotic plaques susceptible to rupture in patients with HIV.
Death rates have been reduced by complete suppression of viral replication by anti-retro viral therapy and the decreased death rates are dependent on the duration of continued viral suppression.
Virologic failure is a result of sub optimal medication adherence and the development of resistance.
Median time from infection to development of AIDS is 8-10 years.
Hematologic manifestations include: anemia, thrombocytopenia, neutropenia, aids-related lymphomas/lymphoproliferative disorders.
Cytopenias in HIV infection can be caused by HIV infection directly, opportunistic infections, medications for antiviral therapy and infection prophylaxis, hypersplenism, and neoplasms.
Anemia occurs in more than 60% of HIV patients at some point in their disease, with chronic disease being the most frequent cause.
Before antiretrovirals therapy for HIV thrombocytopenia occurred in 10-30% of patients, with primary HIV-associated thrombocytopenia being the most common cause.
Anemia and thrombocytopenia are more common once HIV infections advances to AIDS.
Risk for women acquiring HIV infections is heterosexual sex, accounting for approximately 80% of current infections (2007).
Sexual transmission is the least efficient mode of HIV transmission.
The five-year cumulative incidence of HSIL+ and CIN-2 positive analyses was similar in HIV-infected women and HIV uninfected women who were cytologically normal and oncogenic HPV negative at an enrollment study (Keller MJ et al).
HIV infected women undergoing long-term clinical follow-up who are cytologically normal and oncogenic HPV-negative have a risk of cervical precancer similar to that in HIV uninfected women through five years of follow-up.
Can penetrate normal genital tissue in women and not just through breaks in the skin.
19% of females acquire HIV infections by injection drug use (CDC 2007).
Among males 67% of cases acquired from men having sex with men (2007).
CDC suggests 45% of individuals infected are men having sex with men, 27% are infected with heterosexual contact and 22% are infected with the use of intravenous drugs.
Black men having sex with men have a disproportionately higher burden of disease compared to whites and Hispanics, 46%, 21% and 17%, respectively (CDC).
Incidence of men having sex with men as the cause of HIV infection has been increasing.
It is reported that among black men and especially Hispanic men the incidence of men having sex with men as the cause of HIV infection is much less, which may be due to underreporting.
Late testers often present with opportunistic infections
Incidence of HIV infection among all men having sex with men estimated to be 1.9-3.6%, with a prevalence of 8% by age 20 and 38% predicted prevalence, in the absence of interventions, by age 40.
Prevalence of HIV infection among black men aged 15-22 years having sex with men is about 4% and the projected prevalence by age 40 is 60%.
Approximately half of untreated HIV infected patients will develop AIDS within 10 years.
Goal of therapy in infected patients is the keep CD4+ T-lymphocyte count above 200/L to avoid progression to AIDS and opportunistic infections.
The main obstacle to eradicating HIV with anti-retro viral therapy is the reservoir of latent virus found in long- lived resting memory CD4 T cells: the cells are not actively replicating and the virus is hidden from immune system and invulnerable to antiretrovirals therapy.
Rapid progressors have a rapid decline of CD4+ T lymphocyte cell count, poorly produce neutralizing antibodies and develop AIDS in a few years.
Long-term nonprogressors, defined as individuals who remain healthy with CD4 cell counts exceeding 500/uL for 10 or more years without antiretroviral treatment.
Only a small number of long-term nonprogressors have RNA HIV levels below the lower limits of detection.
The CD4 count and plasma HIV RNA levels can discriminate independently between rapid and slow progressors.
Adult male circumcision decreases the incidence of HIV by men via penile-vaginal intercourse by 48-60% over a median follow-up time of 18months (McNeil).
Primary infection induces depletion of CD4+ T cells in the gastrointestinal tract.
The initial stage of an acute HIV infection is of short duration, measured in weeks to months and is difficult to diagnose.
Without treatment most patients develop acquired immunodeficiency syndrome within 10 years of infection.
Anti-retro viral therapy delays progression of disease and increases length of survival, but is most effective when initiated during the asymptomatic phase of the disease.
It is estimated that an HIV-positive person age 25 who receives adequate care will survive an additional 39 years.
The acute HIV infection is associated with high levels of virus.
In the acute phase of illness, the large amount of virus in newly infected individuals will renders them highly infectious.
Acute infection resolves relatively quickly, and evolves without treatment, into a state of chronic infection with relatively stable and lower levels of viremia that can remain relatively constant for years.
Following the acute phase risk of transmission, compared to that of the acute infection, the risk of transmission is much lower.
Patients with late diagnosis have missed the opportunity for early treatment when they are asymptomatic and for the prevention of transmission to others plus they have a shortened life expectancy: Therefore early HIV testing reduces the spread of disease, extend life expectancy, and reduces the cost of care.
The median duration of untreated chronic HIV infection stage is eight years, and the can we have a two fraction of transmissions of infection that occurred during this and of time is significant.
The third phase of untreated disease the results in advanced stage of AIDS associated with a dramatic increase in viremia and increased risk of transmission of disease.
The frequency with which a person with acute HIV infection and transmits the disease tends on their personal behavior.
A risk factor for the development of heart failure, in that ongoing viral replication is the highest associated with higher risk (Butt AA et al).
HIV-RNA levels, low CD4 lymphocyte counts, are associated with increased risk of cardiovascular disease in HIV.
The risk of sexual transmission of HIV is negotiable, if an infected individual as an undetectable viral load up after six months of anti-retro viral therapy.
Antiviral therapy is approximately 99% effective in blocking transmission of HIV.
HIV treatment guidelines recommend antiretroviral therapy should be started when CD4 cell count reaches 350 cells/microliter.
More than 40% of HIV infections in children in sub-Saharan Africa are acquired from breast milk.
Antiretroviral regimens in breast feeding infants or lactating mothers decrease postnatal acquisition of HIV-1: It is possible to eliminate new perinatal HIV-1 infections by using antiretroviral therapy for maternal health or adding postpartum prophylaxis to antepartum and intrapartum prophylaxis,
In a randomized double blind controlled trial of high-dose versus standard dose multivitamin supplementation for 24 months and 3418 patients with HIV initiating HAART therapy: there was no decrease in HIV disease progression or death, but they may have been an increase in ALT levels (Isanaka S et al).
Increasing risk of disease progression and AIDS when increasing plasma level of HIV RNA, as it is inversely associated with CD4 depletion, suggesting HIV replication within CD4 cells leads to accelerated destruction os such cells.
Infections should be considered when patients present with opportunistic infections, have cancers that are associated with HIV positivity, have sexually transmitted disease, herpes zoster, oral candidiasis, or have high-risk behavior.
In HIV-infected men it is associated with a slight transient decrease in the CD4 cell count and an increase in viral load, implying that syphilis may increase the risk of HIV transmission, even in patients receiving antiretroviral therapy and with the viral load less than 500 copies/mL(Jarzebowski W et al).
Truvada as an antiretroviral preexposure prophylaxis reduces the risk of HIV acquisition among men having sex with men, and among heterosexuals.
Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg) for HIV prevention was associated with a significant decline in new diagnoses across the United States.
Truvada approved for preexposure prophylaxis of HIV for adults at high risk.
Daily use of antiretroviral drugs can reduce the risk of HIV acquisition through sexual interourse.
Shedding of herpes simplex virus occurs from the genitals in patients with HIV infection often when they have no symptoms or observable lesions.
HSV- 2 may increase the infectiousness of HIV.
HSV encoded proteins bind HIV in co-infected cells and directly promote transcription of HIV.
Most individuals with HIV infection are also infected with herpes simplex virus type 2, and it is frequently reactivated and associated with increased levels of HIV in plasma and genital lesions.
The risk of transmission of HIV-1 to sexual partners is 4 fold among HIV patients with a symptomatic genital ulcer, compared with HIV patients without a genital ulcer: the majority of genital ulcers are related to HSV-2 infection (Gray RH).
Clinical trials reveal that daily treatment for HSV-2 for 8-12 weeks can reduce plasma HIV-1 levels by 0.25 to 0.50 log10 copies per mL.
Daily acyclovir does not reduce risk of transmission of HIV-1 despite reductions in plasma HIV-1 levels and a 73% reduction in the occurrence of HSV-2 genital ulcers (Partners in Prevention HSV/HIV Transmission Study Team).
Causes involution of thymus in children and adults leading to a depletion of thymocytes.
5-10% are long-term nonprogressors.
Long-term nonprogressors maintain CD4+ T cell counts at 500 cell/mL or greater, control viral replication in the absence of treatment, are able to mount cell and humoral responses, can produce neutralizing andtibodies and have healthy clinical status for 7-10 years.
Strong correlation between certain HLA class I alleles and nonprogressive HIV infection.
Early seroconverters have a lower proportion of HIV-specific IgG in their serum than those with long-term infections.
The presence of genital ulcerative disease increases the risk of HIV transmission 2-5 fold.
Infections of the urethra or cervix with Neisseria gonorrhoeae or Chlamydia trachomatis increase the infectiousness of HIV by increasing the viral load in genital secretions.
Approximately 10% of all HIV-infected persons are rapid progressors who develop AIDS within 5 years of infection with HIV.
Strong correlation between the amount of HIV-1 circulating in the blood and the rate at which AIDS develops.
Symptomatic neurological dysfunction develops in more than 50% of individuals infected with HIV.
Viral particles and anti-HIV antibodies have been identified in the CSF of patients with AIDS associated neurological disease.
Dementia clinical disease often correlated with HIV encephalitis and brain findings include monocyte infiltration, infection of brain macrophages and microglia, giant cells, myelin pallor, and astrogliosis.
The number of inflammatory macrophages accumulating in the brain correlates with the degree of dementia.
No significant difference in incidence of brain lesions in patients in the pre- and post HAART eras.
As patients live longer progressive CNS damage is now more common and this is true even if antivirals can cross the blood-brain barrier.
Dementia characterized by cognitive, behavioral, and motor abnormalities affecting up to 11% of infected patients in the HAART era.
The prevalence of HIV-associated dementia has decreased with effective anti-HIV therapy.
CNS is a sanctuary site for HIV and there is poor penetration of antiviral drugs into the CNS.
Neurological damage may reflect unchecked HIV replication and monocyte cytokine release in CSF.
Staphylococcus aureus is the most common cutaneous and systemic bacterial infectious agent in HIV+ patients.
Respiratory infections most common indication for ICU admissions and include Pneumocystis pneumonia, bacterial pneumonia, tuberculosis, emphysema and COPD.
Immune thrombocytopenia common complication of HIV infection with autoantibodies that recognized a restricted peptide sequence GPIIIa49-66 in platelet membrane glycoprotein IIIa.
Immune reconstitution syndromes for pneumocystis and tuberculosis can occur with paradoxical worsening with the initiation of antiretroviral therapy which causes an exuberant inflammatory response to these agents.
Tuberculosis is the most common opportunistic disease, and most common cause of death in patients with HIV infection in developing countries(Mukadi YD).
The Starting Antiretroviral Therapy at Three Points in (SAPIT) trial determined that the initiation of antiretroviral therapy during tuberculosis therapy signficantly improved survival (Abdool Karim, SS).
Trials have shown preventive treatment of HIV infected patients with INH for 6-12 months or a combination of INH and rifampin for 3 months reduces the risk of tuberculosis by 32-64%.
Primary isoniazid prophylaxis does not improve tuberculosis disease free survival among HIV infected children or tuberculosis infection free survival among HIV uninfected children immunized with BCG vaccine (Madhi SA et al).
A trial to prevent tuberculosis in HIV patients comparing 12 weeks of rifapentine plus INH, rifampin plus INH, INH daily for 6 years or INH for 6 months: all regimens were effective, but no regimen was superior to 6 months of INH (Martinson NA et al).
Among HIV infected adults with CD4+ T cell counts of 200 per cubic millimeter or lower initiating antiretroviral therapy two weeks after the start of tuberculosis treatment significantly improves survival compared with individuals treated later, at eight weeks (Blanc FX e al).
Diagnosis of reconstitution syndrome requires exclusion of other causes of respiratory failure.
HIV positive patients have a higher risk for anal malignancies, particularly squamous cell cancer of the anus or the precursor lesion squamous cell carcinoma in situ.
Positive patients have a 45-fold relative risk of developing gliomas.
Positive patients have a 60-fold relative risk of developing non-Hodgkin’s lymphoma.
Infected patients have a lifetime risk of developing non-Hodgkin’s lymphoma estimated between 5-20%.
One-third of patients with HIV also have hepatitis C infection.
Estimated 150,000 to 300,0000 people infected with both HIV and hepatitis C, representing 15-30% of all people living with HIV infection and 70-90% of injection drug users.
All patients with HIV infection should be tested for hepatitis C.
Patients at risk for HIV are at higher risk for acute and chronic hepatitis B.
Coinfection with hepatitis B associated with a decrease in survival time.
Coinfection with malaria results in increasing viral load and falling CD4 cell counts.
At least 1o to the 10th billion virions are produced and cleared each day in infected persons.
Half-life of virions in circulations is less than 6 hours and the half-life of actively infected CD4+Tcells is 1.5 days.
Lower mortality rate among patients coinfected with HIV and GBV-C.
Associated non-Hodgkin’s lymphoma median survival of 6-11 months.
About 80% of HIV transmission now occurs via vaginal intercourse.
Proportion of patients with HIV associated kidney disease is as high as 30%, but with HAART the progression of nephropathy has slowed.
Transmission of HIV and sexually transmitted disease is more efficient from men to women than vice versa.
Estimated that without rate 15-30% of babies born to HIV-seropositive mothers will be HIV-infected.
Zidovudine as monotherapy decreases by two-thirds the maternal-infant transmission rate.
Frequency of maternal-infant transmission with use of lamivudine-zidovudine is 1.6% compared to zidovudine monotherapy with a 6.8% transmission rate.
Elective cesarean delivery decreases transmission rate by two-thirds compared to other types of delivery.
18% of associated non-Hodgkin’s lymphomas are primary central nervous system lymphoma associated with Epstein-Barr virus.
Growth hormone secretion is reduced in patients with HIV infection and abdominal fat accumulation and relative growth hormone deficiency is seen in one third of such patients.
Relative deficiency common among patients with HIV and lipodystrophy and is seen mostly in men with HIV and abdominal fat accumulation.
Positive pregnant females should receive zidovudine monotherapy beginning at 14 to 34 weeks’ gestation, intravenously during labor and, orally to the newborn for 6 weeks.
Perinatal transmission rates of 4-10% in the U.S.
HIV transmission rate to newborns is now less than 1% for women treated during pregnancy (Coovadia H et al).
Standard recommendations include immunization for hepatitis A and hepatitis B virus.
Susceptibility of CD4+ helper T-cells because of its high affinity for the viral-envelope glycoprotein.
Profound loss of CD4+ T-cells the main finding in HIV.
May be able to mediate depletion of gut CD4+ T cells by impairing integrin alpha4beta7 which directs such cells to the gut.
A small population of CD4+ T-cells stop proliferating and allows persistence of HIV associated with a latent reservoir of virus.
Clinical trials demonstrate survival benefit with antiretroviral therapy for patients with severe immunodeficiency.
Antiretroviral therapy for asymptomatic patients with CD4-cell counts of greater than 200/’L may not be associated with a survival advantage.
Does reach semen and replication takes place in T-cells and macrophages present.
With the introduction of highly active antiretroviral therapy (HAART) there has been a significant decline in Kaposi’s sarcoma and the a lesser extent non-Hodgkin’s lymphoma.
With the introduction of highly active antiretroviral therapy (HAART) there has been an increase in Hodgkin’s disease, lung cancer, skin cancers, anogenital cancer and head and neck malignancies.
Goal of antiviral therapy is the suppression of viremia to less than 50 copies/mL of HIV-RNA, the limit of detection by most assays.
Triple drug antiretroviral treatment decreases the risk of invasive pneumococcal disease.
Pneumococcal vaccination decreases risk of pneumococcal infection in patients vaccinated when their CD4+ cell count is greater than 500/ microL.
Structured interruptions in treatment are attempts at reducing toxicity and cost of continuous therapy, but is not yet accepted routine practice as it may be associated with higher virological failure rates.
SMART (Strategies for Management of Antiretroviral Therapy) study utilized strategy of intermittent antiretroviral therapy based on CD4+ counts in patients with chronic infection, evaluating 5400 patients with CD4+ counts greater than 350 cells per cc.
SMART study randomized patients to continuous antiretroviral therapy or to intermittent antiretroviral therapy administered when the CD4+ count fell to 250 cells per cc and stopped when the count rose to more than 350 cells per cc.
SMART study revealed that patients in the continuous group received antiretroviral treatment 94% of the time and the conservative group received therapy 33% of the time.
Adverse reactions to antiviral drugs are are among the most common reasons for changing or discontinuing such drugs, and cause poor adherence to medication program.
The presence of adverse laboratory events with antiviral therapy associated with increased mortality during 6 years of follow-up (Keiser O).
Toxic effects from antiviral infections range from 3% with combined tenofir, emitricitabine with atazanavir, 4% with tenofir, emitricitabine with efavirenz, and 9% for zidovudine, lamivudine, and efavirenz (Gallant JE).
The CDC now recommends HIV screening for all individuals aged 13-64 years as part of routine medical care.
Infection is not inevitable or instantaneous after exposure.
After exposure of HIV via percutaneous or mucous membranes there is a window of approximately 3-5 days before durable infection is established, allowing an opportunity to decreases the transmission risk by post exposure prophylaxis.
The average risk of infection transmission by an occupational needle stick involving an HIV infected patients is about 0.3%.
The average per contact transmission rate after unprotected receptive anal intercourse is 1-5%.
The average per contact transmission rate for unprotected insertive anal intercourse and receptive vaginal intercourse is about 0.1-1%, similar to the needle stick rate.
The per contact transmission rate after unprotected insertive vaginal intercourse is less than 0.1%
The average per contact transmission rate is increased when sexually exposure is associated with trauma, genital ulceration and cervical ectopy.
Applying estriol cream to the inner foreskin increases keratinization within 24 hours and persists for at least 5 days, possibly resulting in increased protection against HIV infection.
The risk of receptive oral sex has been difficult to quantify but is probable infrequent.
Range of CD4+ cells define conditions of HIV complications by stage of immunosuppression.
HIV depletes CD4 lymphocytes, leading to dysfunction of both cellular and humoral immunity and increases the risk of viral, bacterial, and fungal infections.
CD4+cells >500 cells/ul-a normal range with no symptoms except during primary HIV infection.
CD4+ cells 350-500 cells/ul-usually no symptoms but may have a slight increased risk of tuberculosis and long periods of time in this range may modestly increases the risk of cancer and heart disease.
CD4+cells 200-350 cells/ul-increased risk of shingles, bacterial pneumonia, oral and vaginal candidiasis, fatigue, oral hairy leukoplakia, tuberculosis Kaposi’s sarcoma and Mycobacterium infections.
CD4+cells 100-200 cells/ul-cervical cancer, lymphomas, pseudocysts carinii pneumonia, toxoplasmosis, coccidioidomycosis, histoplasmosis and recurrent pneumonia.
CD4+cells <100 cells/ul-esophageal and bronchial candidiasis, cryptosporidiosis, Cytomegalovirus infections, herpes simplex, CNS lymphoma mycobacterium infections and progressive multifocal leukoencephalopathy.
Incidence and prevalence of renal disease is increasing in older patients because of the widespread use of antiretroviral therapy.
Despite anti-anti-retroviral therapy, CD4 positive T-lymphocytes in individuals infected with HIV remain lower than a control group without HIV.
HIV induces B cell activation and paradoxically causes an inappropriate response to stimulation, which results in sub optimal primary and secondary responses to vaccination.
This change is a similar to the immunosenescence scene in elderly people and is most likely associated with persistent inflammation.
Fracture rates among HIV-infected patients is 2 to 4 times higher than in the general public.
In two trials the Subcutaneous Recombinant, Human Interleukin-2 in HIV Infected Patients with Low CD4 positive Counts under Active Anti-Retro Viral therapy (SILCAAT) and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) revealed a sustained increase in CD4 positive cell count, as compared to anti-retroviral therapy alone, interleukin 2+ anti-retroviral therapy but yielded no clinical benefit.
Regimens containing a ritonavir-boosted protease inhibitor with two nucleoside transcriptase inhibitors (NRTIs) or an non-nucleotide reverse transcriptase inhibitor (NNTRI) with two NRTIs are the recommended first-line treatments.
Vast majority of patients receive treatment with a 3-drug combination of efavinenz, emitricitabine, and tenofovir available as a single pill, taken once daily (Atripla).
The protease inhibitor lopinavir with its pharmacological booster ritonavir is now the most widely prescribed ritonavir boosted protease inhibitor in children.
In studies of anti-retro viral treatment of naI’ve participants initiating nonnucleoside reverse transcriptase inhibitor based regimens revealed that the presence of minority HIV-one resistant mutations is associated with a greater than twofold increase risk of first line antiretroviral treatment failure (Li JZ et al).
Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression (ATLAS and FLAIR trials).
Chronic immune activation occurs in HIV infection and is not completely abrogated by ART.
Slight elevations of pro inflammatory and pro coagulation biomarkers are associated with poor outcomes and include increased mortality, suggesting chronic immune activation and dysfunction seen in chronic HIV disease can lead to comorbidities.
Patients with HIV including those who have received ART have an increased risk of ischemic heart disease and other serious cardiovascular process.
Patients with HIV receiving ART have an increased risk for bone mineral density loss.