The virus targets the immune system.

HIV is most commonly transmitted through having unprotected sex with someone with HIV who isn't taking HIV treatment. Unprotected sex means having sex without taking HIV PrEP or using condoms.

HIV can also be transmitted by:

• sharing infected needles and other injecting equipment
• an HIV-positive mother to her child during pregnancy, birth and breastfeeding

All pregnant women are offered an HIV test and if the virus is found, they can be offered treatment which virtually eliminates risk to their child during pregnancy and birth.

People who take HIV treatment and whose virus level is undetectable can't pass HIV on to others. Although there is no cure for HIV yet, people living with HIV who take their treatment should have normal lifespans and live in good health.

Without treatment, people with HIV will eventually become unwell. HIV can be fatal if it's not detected and treated in time to allow the immune system to repair. It's extremely important to test for HIV if you think you've been exposed.

To enter a host cell, HIV binds to a CD4 receptor and a coreceptor (either CCR5 or CXCR4) on the host cell.

A protein found primarily on the surface of CD4 T lymphocytes (CD4 cells).

AIDS

AIDS is the consequence of infection with HIV-1, a retrovirus that infects multiple cell lines, including lymphocytes, monocytes, macrophages, and dendritic cells.

With HIV infection, there is an absolute reduction of CD4 T lymphocytes, an accompanying deficit in CD4 T-lymphocyte function, and an associated increase in CD8 cytotoxic T lymphocytes (CTLs). In addition to the cell-mediated immune defects, B-lymphocyte function is altered such that many infected individuals have marked hypergammaglobulinemia but impaired specific antibody responses. The resultant immunosuppression predisposes patients to the constellation of opportunistic infections that characterizes AIDS.

The loss of CD4 cells seen in HIV infection is the result of multiple mechanisms, including (1) autoimmune destruction, (2) direct viral infection and destruction, (3) fusion and formation into multinucleated giant cells, (4) toxicity of viral proteins to CD4 T lymphocytes and hematopoietic precursors, and (5) apoptosis (programmed cell death).

The clinical manifestations of HIV infection and AIDS are the direct consequence of progressive and severe immunosuppression and can be correlated with the degree of CD4 T-lymphocyte destruction. HIV infection may present as an acute, self-limited febrile syndrome. This is often followed by a long, clinically silent period, sometimes associated with generalized lymphadenopathy. The time course of disease progression may vary; the majority of individuals remain asymptomatic for 5–10 years. Approximately 70% of HIV-infected individuals will develop AIDS after a decade of infection. Approximately 10% of those infected manifest rapid progression to AIDS within 5 years after infection. A minority of individuals are “long-term nonprogressors.” Genetic factors, host cytotoxic immune responses, and viral load and virulence all appear to have an impact on susceptibility to infection and the rate of disease progression. Multidrug antiretroviral therapy has dramatically changed this natural history and markedly prolonged survival.

As the CD4 count declines, the incidence of infection increases. At CD4 counts between 200/μL and 500/μL, patients are at an increased risk for bacterial infections, including pneumonia and sinusitis. As CD4 counts continue to drop—generally below 250/μL—they are at high risk for opportunistic infections such as pneumocystic pneumonia, candidiasis, toxoplasmosis, cryptococcal meningitis, cytomegalovirus (CMV) retinitis, and Mycobacterium avium complex infection. HIV-infected individuals are also at increased risk for certain malignancies, including Kaposi sarcoma, non-Hodgkin lymphoma, primary CNS lymphoma, invasive cervical carcinoma, and anal squamous cell carcinoma. Other manifestations of AIDS include AIDS dementia complex, peripheral neuropathy, monoarticular and polyarticular arthritides, unexplained fevers, and weight loss. Since patients are living longer due to potent antiretroviral therapies (ART), cardiovascular complications are more prominent. ART has been associated with dyslipidemia and metabolic abnormalities including insulin resistance. HIV infection may be atherogenic as well, through effects on lipids and proinflammatory mechanisms.

HIV is a long term health condition which is now very easy to manage.

Start immunizations regardless of CD4 count or viral load.

HIV infection is now known to cause heightened levels of immune activation and inflammation, which may increase the incidence of myocardial infarction and malignancy independent of CD4 count. There is increasing evidence to support the theory that untreated HIV infection may lead to accelerated aging, with premature loss of bone density and neurocognitive decline. In addition, recent studies such as the HPTN 052 study showed a 96% decrease in HIV transmission validating “treatment as prevention.” Successful suppression of viral replication by antiretroviral therapy mitigates these consequences significantly.]

• Immunizations
• Treatment of Concomittant Diseases

Follow Up

• Absolute CD4 lymphocyte count is widely used for staging HIV disease. 

• Acquired immune deficiency syndrome (AIDS) is defined as a CD4 <200 cells/μL. AIDS represents advanced HIV disease that is associated with opportunistic infections or malignancy in the absence of treatment.

• HIV RNA level (viral load) is used to monitor response to antiretroviral therapy.

 

 

Daily Anti-Tuberculosis Regimen in HIV-Infected Patients Superior to Intermittent Regimens 

by Robert W. Eisinger, PhD, Office of the Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Anthony S. Fauci, MD, Chief, Laboratory of Immunoregulation, Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Update to Chapter 202: Tuberculosis and to Chapter 226: Human Immunodeficiency Virus Disease: AIDS and Related Disorders

Investigators in India report that HIV-infected patients receiving antiretroviral therapy (ART) with pulmonary tuberculosis (TB) treated with a daily anti-tuberculosis (TB) regimen of ethambutol (E), isoniazid (H), rifampicin (R), and pyrazinamide (Z) for 6 months demonstrated higher cure rates and fewer cases of rifampicin resistance compared with patients receiving a thrice-weekly regimen of the same anti-TB drugs.

Treatment for individuals living with HIV and newly diagnosed with pulmonary TB remains a challenge, especially in resource-poor settings, due to the lack of clinical trial data comparing various anti-TB regimens.

Gopalan and colleagues (2018) recently reported the findings from an open-label, parallel-group, randomized clinical trial comparing the safety and efficacy of daily, part-daily (daily during the intensive phase and thrice-weekly during the continuation phase), and intermittent (thrice-weekly during the intensive and continuation phases) anti-TB regimens in HIV-infected patients newly diagnosed with pulmonary TB (NCT00933790). The study was designed to determine the treatment regimen with the lowest rates of treatment failure and acquired rifampicin resistance. The primary outcome for the trial was defined as the proportion of patients who completed treatment and whose sputum cultures were negative for Mycobacterium tuberculosis (Mtb) during the last 2 months of treatment. The authors enrolled 331 adults between September 2009 and January 2016 at 3 sites in southern India. At the time of the clinical trial, the World Health Organization (WHO) treatment guidelines for pulmonary TB recommended a daily or part-daily (daily only during the intensive phase) treatment regimen of EHRZ for 2 months followed by a continuation regimen of HR for 4 months (WHO, 2010). At that time, the Indian Revised National TB Control Program used the thrice-weekly regimen for TB (India Ministry of Health and Family Welfare, 2008).

Study participants were randomized to one of three anti-TB regimens, and stratification was based on baseline CD4+ T lymphocyte counts (<150 cells/µL vs >150 cells/µL) and sputum smear grading (0 and 1+ vs 2+ and 3+). The anti-TB regimens were as follows:

1. Daily in both the intensive and continuation phases of E (800 mg), H (300 mg), R (450/600 mg depending on weight), and Z (1500 mg) for 2 months followed by HR for 4 months in the continuation phase (designated 2EHRZ7/4HR7);

2. Part-daily involving daily E (800 mg), H (300 mg), R (450/600 mg depending on weight), and Z (1500 mg) during the 2-month intensive phase and intermittent (thrice-weekly) H (600 mg) and R (450/600 mg) during the 4-month continuation phase (designated 2EHRZ7/4HR3); and

3. Intermittent (thrice-weekly) E (1200 mg), H (600 mg), R (450/600 mg depending on weight), and Z (1500 mg) during both the 2-month intensive and 4-month continuation phases (designated 2EHRZ3/4HR3).

All study participants also received daily pyridoxine (100 mg) and cotrimoxazole double strength. Blood and sputum specimens were collected monthly until 18 months after randomization for detection of Mtb, drug susceptibility testing, complete blood cell count, liver and renal function tests, CD4+ T cell counts, and plasma HIV viral load. The anti-TB drugs were administered under direct observation during weekdays and self-administered over the weekends. Patients not already on ART were started on lamivudine + efavirenz along with either zidovudine, stavudine, or tenofovir between 2 and 8 weeks after starting anti-TB treatment. Patients were excluded from this clinical trial if they were on ART containing protease inhibitors, had significant renal or liver disease, or had rifampicin-resistant TB at baseline.

The authors report that the study was terminated by the data safety monitoring committee after the second interim analysis due to the difference in the outcome measure between the daily regimen (91%), part-daily regimen (80%), and intermittent regimen (77%) groups. The outcome differences between the daily and intermittent regimen groups were statistically significant (14%; 95% confidence interval, 3.9–25). There were 18 deaths across the groups during anti-TB therapy, including 4 deaths in the daily group, 9 deaths in the part-daily group, and 5 deaths in the intermittent group. While there were no drug-induced deaths, adverse reactions were reported in all 3 groups including 27% of study participants in the daily group, 21% in the part-daily group, and 17% in the intermittent group. Hepatoxicity was seen more frequently (9%) in the daily regimen group compared with 2% in the intermittent regimen group. All cases of jaundice were resolved by 28 days in the daily and part-daily regimen groups and 20 days in the intermittent regimen group. The authors report that TB recurrence was observed in a total of 16 study participants including 6 patients, 4 patients, and 6 patients in daily, part-daily, and intermittent regimen groups, respectively. There were also 82 cases of immune reconstitution inflammatory syndrome across the 3 groups (27 patients in the daily group, 21 patients in the part-daily group, and 34 patients in the intermittent group), with 68% of these cases classified as extrapulmonary lesions and 32% as pulmonary lesions.

Gopalan and colleagues conclude that the daily 6-month anti-TB regimen (2EHRZ7/4HR7) in HIV-infected patients on ART with newly diagnosed pulmonary TB resulted in higher cure rates and prevented development of acquired rifampicin resistance compared with the 6-month thrice-weekly (2EHRZ3/4HR3) regimen. They also noted that higher CD4+ T cell counts at the end of the intensive phase, instead of the levels at baseline, were associated with successful outcomes in this clinical trial. The authors reported that even study participants with CD4+ cell counts <150 cells/µL had better survival rates with the daily regimen compared with the other two anti-TB regimens. The authors suggest that the high incidence of hepatotoxic effects seen across all 3 regimens may be due to several factors including prior alcohol intake, advanced immunodeficiency, extrapulmonary site involvement, and coadministration of ART with the daily intensive phase of the anti-TB regimen, which requires closer monitoring of liver function. They also note that the part-daily regimen had no benefits over the intermittent regimen with regard to efficacy or tolerability; however, the part-daily regimen did prevent more cases of acquired rifampicin resistance.

Current U.S. treatment guidelines for individuals with HIV infection and pulmonary TB recommend daily directly observed therapy (DOT) for a 2-month intensive phase with ethambutol, isoniazid, rifampicin, and pyrazinamide followed by daily DOT dosing of isoniazid and rifampin during the 4-month continuation phase (Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents, 2017). As newer antiretrovirals are incorporated into first-line therapies, additional clinical studies will be needed to ensure that individuals with HIV and pulmonary TB are provided the appropriate anti-TB treatment regimens with minimum drug-drug interactions and toxicities. In a commentary accompanying the Gopalan report, Zuger (2018) discusses the continued need for alternatives to daily anti-TB treatment regimens that can reduce development of anti-TB drug resistance, adverse events, and pill burden.

References

Gopalan  N  et al: Daily vs intermittent antituberculosis therapy for pulmonary tuberculosis in patients with HIV: A randomized clinical trial. JAMA Intern Med 178:485; 2018. 
[PubMed: 29507938] 

India Ministry of Health and Family Welfare: TB India 2008—RNTCP status report: I am stopping TB. Available at: tbcindia.gov.in/showfile.php?lid=2920. 
[PubMed: 29641576] 

National Institutes of Health: Comparing daily vs Intermittent Regimen of ATT in HIV with Pulmonary Tuberculosis. Available at: clinicaltrials.gov/ct2/show/NCT00933790.

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents: Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. 2017. Available at: aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportunistic-infection/325/tb.

World Health Organization: Treatment of Tuberculosis Guidelines. Fourth edition. Geneva, World Health Organization, 2010. Available at: who.int/tb/publications/2010/9789241547833/en/.

Zuger  A: Daily treatment for HIV-associated TB is still best. NEJM Journal Watch, March 26, 2018. Available at: jwatch.org/na46258/2018/03/26/daily-treatment-hiv-associated-tb-still-best.

 

Complications of Injecting Drug Use

• Local problems—Abscess (Figures 240-2 
  

  A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of ­Richard P. Usatine, MD.)

  and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2
  • IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
  • Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
• IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
  • Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.