Treatment Recommendations for HIV-Infected Patients With Co-infections

Updated: Dec 16, 2019
  • Author: Syed Faisal Mahmood, MBBS; Chief Editor: Michelle R Salvaggio, MD, FACP  more...
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Infection with human immunodeficiency virus (HIV) can result in immunosuppression, allowing opportunistic pathogens to cause disease. Certain opportunistic infections are associated with increases in viral load, which may accelerate HIV progression or increase transmission of HIV. [1, 2, 3] Opportunistic infections are a major cause of morbidity and mortality in HIV-infected patients; however, with the availability of antiretroviral therapy, there is a decline in the incidence of opportunistic infections in both low- and high-income countries. [4, 5]


Treatment of Hepatitis B Virus With Coexisting HIV Infection

Patients with HIV infection are at a greater risk for hepatitis B virus (HBV) infection, due to the common route of transmission.

Patients with HIV infection are at a higher risk for developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma than patients diagnosed with only chronic HBV infection. [6, 7]

Treatment of HIV infection may improve the virological, histological, and clinical evolution of chronic HBV infection. [8]

Several antiretroviral agents, such as emtricitabine, lamivudine, and tenofovir, have activity against HIV and HBV, while others, such as entecavir, have limited activity against HIV but lead to the development of HIV-resistant strains if used alone. [9]

Prior to the initiation of antiretroviral therapy, all patients who test positive for hepatitis B surface antigen (HBsAg) should be tested for HBV deoxyribonucleic acid (DNA) using a quantitative assay to determine the level of HBV replication. [6]

Chronic HBV is defined as testing positive for HBsAg for more than 6 months [10] ; patients with chronic HBV infection already receiving antiretroviral therapy active against HBV should undergo quantitative HBV DNA testing every 6-12 months. [6]

Routine screening and immunization are recommended for all HIV-infected patients to prevent primary HBV infection; however, the immune response to HBV vaccine is lower in patients with HIV infection than in uninfected patients, and postvaccination HBsAg must be tested to document immunity. [11, 12, 13, 14]

All patients with HBV/HIV coinfection must be assessed for hepatitis A virus (HAV) immunity and vaccinated if negative. [14]

Recommendations for patients requiring hepatitis B virus and HIV treatment

In patients with HIV and HBV coinfection, HBV infection should be treated only in conjunction with HIV infection. Treatment of HBV infection alone without addressing the HIV infection will lead to emergence of HIV strains that are resistant to nucleoside reverse-transcriptase inhibitors (NRTI). [15]

Only tenofovir is fully active for the treatment of patients with known or suspected lamivudine-resistant HBV infection [16]

In treatment-naive patients with HIV/HBV coinfection, a regimen containing TDF plus FTC or TDF plus 3TC should be used as the backbone of HIV therapy.

If TDF cannot be used, entecavir may be used to treat HBV infection; however, owing to its weak activity against HIV, [6] this is not considered an active component of the antiretroviral regimen. Lamivudine-resistant strains of HBV may rapidly develop resistance; therefore, a higher dose (1 g/day) is recommended with more frequent HBV viral load monitoring.

If the HIV therapy requires modification (eg, due to HIV virologic failure), the HBV-active antiretroviral must be continued and new antiretrovirals added to achieve HIV viral suppression.


Treatment of Hepatitis C Virus With Coexisting HIV Infection

Increased rates of cirrhosis in patients with hepatitis C virus (HCV) are attributable to various factors, including older age, alcoholism, male sex, and HIV infection; higher rates of progression to cirrhosis are seen in patients with HCV/HIV. [6]

HCV infection in patients with HIV infection can have significant consequences, including liver disease progression, cirrhosis, increased rates of end-stage liver disease, and shortened lifespan after hepatic decompensation. [6, 17]

Initial evaluation and treatment recommendations for patients with hepatitis C virus/HIV coinfections

Prior to initiating antiretroviral therapy, screen patients with HIV infection for HCV using sensitive immunoassays licensed for the detection of antibody to HCV in blood; to confirm the presence of chronic infection, persons who are HCV seropositive should be tested for HCV ribonucleic acid (RNA) using a qualitative or quantitative assay. [18]

Advise patients with HCV/HIV to avoid alcohol and receive HAV and HBV vaccines, if screened negative via serology. [6]

Drug-induced liver injury (DILI) following antiretroviral therapy is more common in HIV/HCV coinfection; eradication of HCV infection may decrease the likelihood of antiretrovirus-associated DILI. [6]

It is important to monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at 1 month and then every 3 months after the initiation of antiretroviral therapy.

Antiretroviral therapy should be started in persons co-infected with HCV and HIV in accordance with the recommendations for initiating antiretroviral therapy in treatment-naive patients. [19, 20, 21]

Special considerations for antiretroviral therapy in patients with hepatitis C virus/HIV coinfection

See the list below:

Patients receiving or considering therapy with ribavirin should avoid didanosine, stavudine, and zidovudine.

Use caution with antiretroviral agents with the greatest risk of DILI (eg, nevirapine).

Assess cirrhotic patients for signs of liver decompensation according to the Child-Turcotte-Pugh classification system; hepatically metabolized antiretroviral drugs may require dose modification or avoidance in patients with Child-Pugh class B and C disease. [6]

Treatment of both HCV and HIV can be complicated by drug interactions, drug toxicities, and pill burden. Many of the newer directly acting anti-HCV drugs have significant interactions with antiretroviral agents; however, ledipasvir with sofosbuvir and daclatasvir plus sofosbuvir have been demonstrated as efficacious. [22, 23]

The timing of HCV treatment in relation to HIV treatment depends on the immune status of the patient, as follows: [15]

  • In patients with higher CD4 counts (>500 cells/µL), HCV treatment before antiretroviral therapy may be considered to avoid drug-drug interactions.
  • In patients with CD4 counts between 500 and 200 cells/µL, the decision to start HCV treatment before antiretroviral therapy should be individualized.
  • In patients with CD4 counts between 500 and 200 cells/µL, prompt initiation of antiretroviral therapy is recommended.

Treatment Recommendations for Tuberculosis and HIV Infection

Tuberculosis (TB) is caused by Mycobacterium tuberculosis, which commonly affects the lungs, although it can also affect other parts of the body.

Patients with HIV infection are more likely to be affected by TB; HIV infection may increase the risk of progression from latent to active TB.

All patients should be tested for latent TB infection (LTBI) at the time of HIV diagnosis using skin testing or interferon-gamma release assay (IGRA).

Patients diagnosed with active TB should be started on TB treatment as soon as possible; recommendations for anti-TB treatment regimens in adults infected with HIV follow the same principles as recommendations for adults without HIV infection. Standard anti-TB regimens include isoniazid plus a rifamycin (rifampin or rifabutin) plus pyrazinamide plus ethambutol for 2 months, followed by isoniazid plus a rifamycin for 4-7 months. [6, 4, 24]

Weekly isoniazid plus rifapentine for 3 months (3HP) is now recommended as an alternative regimen for LTBI when provided as directly observed or self-administered therapy. Patients with LTBI who cannot receive isoniazid should receive daily rifampin monotherapy for four months. [25]

Symptoms may worsen among patients with active TB upon initiation of antiretroviral therapy owing to immune reconstitution inflammatory syndrome (IRIS). Patients at high risk for IRIS should receive pre-emptive adjunctive prednisone with the initiation of ART. [25]

The timing of antiretroviral therapy and anti-TB therapy must therefore be taken into consideration, as follows:

  • For patients with a CD4 count of less than 200 cells/µL, those with multidrug-resistant (MDR) TB, or those with CNS disease, antiretroviral therapy should be initiated within 2-4 weeks of starting TB treatment.
  • For patients with a CD4 count of 200-500 cells/µL, antiretroviral therapy should be initiated within 2-4 weeks or at least by 8 weeks after the commencement of TB therapy.
  • For patients with a CD4 count above 500 cells/µL, most experts recommend starting antiretroviral within 8 weeks of TB therapy. [6, 15]

Decisions to use a regimen containing either rifampin or rifabutin should be made after considering potential drug interactions. Rifamycins, such as rifampin and rifabutin, are a major part of anti-TB regimens; rifampin is a strong inducer of CYP3A enzymes and is associated with drug interactions with antiretroviral agents, such as protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs); rifabutin is a weak inducer and can be used as an alternative to rifampin. [6, 4] However, dose adjustments must always be considered. For patients undergoing treatment for active TB, starting antiretroviral therapy with efavirenz or an integrase strand transfer inhibitor (INSTI) is preferred, owing to fewer interactions with rifampin. [6, 4] Nevirapine-based regimens should be avoided owing to a higher rate of treatment failure.

There is a potential for drug-induced hepatitis with antiretroviral and anti-TB drugs, so frequent monitoring is required for signs and symptoms of hepatitis; monitoring of liver enzymes is also necessary.