V. Prevention

In the absence of more effective antiviral therapy, strategies are needed to reduce the impact of bacterial infections on morbidity and mortality during the course of HIV infection. Research to date has identified injection drug use, lower CD4 counts, and indwelling vascular catheters as risk factors for developing serious bacterial infections. Data from prospective studies are needed to determine whether additional factors may help identify patients at highest risk for developing bacterial infections. If high-risk individuals can be identified, then more targeted strategies to reduce the impact of bacterial infections can be developed. Possible interventions include bacterial vaccines, eradication of nasal staphylococcus carriage among patients with indwelling venous catheters,⁽⁶³⁾ chronic administration of antibacterial agents, use of growth factors, and intravenous immunoglobulins. Recent developments in some of these areas are summarized below.

A. Pneumococcal Vaccination

Administration of the polyvalent pneumococcal vaccine is currently recommended for patients with HIV infection.⁽⁸⁵⁾ Several studies have demonstrated that HIV-infected patients develop measurable antibody after vaccination.^(86-89) In one recent study, HIV-infected adults were found to have lower postvaccination antibody titers than controls, however, the difference did not reach statistical significance.⁽⁹⁰⁾ In this study, 76% of the patients with CD4 counts below 100/mm³ had a twofold or greater increase in antibody after vaccination compared with 86% of those with counts of 101-300/mm³ and 87% of those with CD4 counts of >300/mm³. In another study, response to vaccination with the polyvalent pneumococcal vaccine did not correlate with CD4 count; however, among patients with CD4 counts of >200/mm³, response did correlate with a greater T-cell activation index.⁽⁹¹⁾ These authors suggest that response to vaccination may be an indicator of better T-cell function and may be of value clinically.

Attempts to improve response rates to pneumococcal vaccination have included the use of a protein-conjugated vaccine.⁽⁹²⁾ Preliminary results from a randomized comparison of a new conjugate vaccine with the current polysaccharide vaccine suggest that while an augmentation in response is seen in HIV-negative subjects, no enhancement of antibody titer has been observed in HIV-infected subjects.⁽⁹²⁾ Further work is in progress to determine whether boosting with the conjugate vaccine will improve response rates.

There are limited data on the clinical efficacy of the pneumococcal vaccine among HIV-infected adults. In a case-control study, patients who developed invasive pneumococcal infection were less likely to have received the vaccine than matched controls.⁽⁹³⁾ Despite the recommendation that the vaccine be given and the data showing measurable antibody even among patients with advanced disease, one recent study suggests that the vaccine is not being routinely given.⁽⁹⁴⁾ In a review of medical records of more than 9000 HIV-infected adults and adolescents receiving medical care at more than 90 U.S. facilities, only 37% had documented pneumococcal vaccination.⁽⁹⁴⁾ Efforts to increase vaccination rates and to evaluate the efficacy of this strategy are needed.

B. Antibiotic Prophylaxis

Data suggest that trimethoprim-sulfamethoxazole (TMP-SMX), when used for PCP prophylaxis, reduces the risk of bacterial infections.^{(95, 96)} In a randomized trial comparing TMP-SMX with aerosolized pentamidine (ACTG 021), patients randomized to TMP-SMX had significantly fewer bacterial infections (19 infections vs. 38 infections, respectively) and a longer time to the development of a bacterial infection. In this study the most common bacterial infections were pneumonia, bronchitis, and sinusitis.⁽⁹⁵⁾ In a recent retrospective study, patients receiving TMP-SMX were matched with patients receiving aerosolized pentamidine (AP) and data on bacterial infections were abstracted from medical records.⁽⁹⁶⁾ In this study the rate of clfinically diagnosed and microbiologically confirmed bacterial infections as well as the number of days of hospitalization were significantly reduced for patients receiving TMP-SMX compared to those receiving AP.

The impact on bacterial infections of chronic administration of clarithromycin and rifabutin (both with broad-spectrum antibacterial activity) for prophylaxis against Mycobacterium avium complex (MAC) is the focus of an ongoing prospective study (ACTG 815) data should be available in mid-1995. In addition, data from this study should help to identify risk factors for the development of bacterial infections in patients with advanced HIV disease.

Chronic administration of antibiotics may lead to the development of antimicrobial resistance. Recently, there has been concern about the emergence of drug resistance among pneumococcal isolates.⁽⁹⁷⁾ In one report from Spain, antimicrobial susceptibility was determined for 76 isolates of S. pneumoniae.⁽⁹⁸⁾ Pneumococcal strains from HIV-infected patients were less likely than those from uninfected patients to be resistant to penicillin, however, 57% had reduced sensitivity to TMP-SMX compared to 13% of the controls. All HIV-infected patients in this study with TMP-SMX-resistant pneumococcal isolates were receiving chronic TMP-SMX therapy. Further investigation into the relationship between drugs used for prophylaxis in HIV infection and drug-resistant bacterial infections is needed.

C. Intravenous Immunoglobulin

Monthly administration of intravenous immunoglobulin (IVIG) at a dose of 400 mg/kg has been shown to reduce the incidence of serious and minor bacterial infections in children with HIV infection.⁽⁹⁹⁾ Several recently conducted small studies using different doses of intravenous immunoglobulin in adults have yielded conflicting results.^(100-102) In one nonrandomized study using IVIG (1 g/kg monthly) with antiretroviral therapy, the rate of recurrent respiratory infections was reduced in the group receiving IVIG; however, a higher rate of opportunistic infections was also observed among IVIG recipients.⁽¹⁰⁰⁾ In a preliminary report from a randomized study using 400 mg/kg of IVIG (followed by 200 mg/kg/ month), a significant reduction in serious infections and death was reported for the IVIG recipients.⁽¹⁰¹⁾ Additional data from randomized controlled studies targeting patients at highest risk for bacterial infections are needed to determine the role of this expensive parenteral therapy in the management of HIV disease.