Abstract
Introduction
Opportunistic infections can occur in up to 40% of people with HIV infection and a CD4 count less than 250/mm3, although the risks are much lower with use of highly active antiretroviral treatment.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylaxis for Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis? What are the effects of antituberculosis prophylaxis in people with HIV infection? What are the effects of prophylaxis for disseminated Mycobacterium avium complex (MAC) disease for people with, and without, previous MAC disease? What are the effects of prophylaxis for cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV)? What are the effects of prophylaxis for invasive fungal disease in people with, and without, previous fungal disease? What are the effects of discontinuing prophylaxis against opportunistic pathogens in people on highly active antiretroviral treatment (HAART)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aciclovir; antituberculosis prophylaxis; atovaquone; azithromycin (alone or plus rifabutin); clarithromycin (alone, or plus rifabutin and ethambutol); discontinuing prophylaxis for CMV, MAC, and PCP; ethambutol added to clarithromycin; famciclovir; fluconazole; isoniazid; itraconazole; oral ganciclovir; rifabutin (alone or plus macrolides); trimethoprim–sulfamethoxazole; and valaciclovir.
Key Points
Opportunistic infections can occur in up to 40% of people with HIV infection and a CD4 count less than 250/mm3, although the risks are much lower with use of highly active antiretroviral treatment (HAART).
HAART has reduced the rate of Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, and other opportunistic infections, so the absolute benefits of prophylactic regimens for opportunistic infections are probably smaller in people with HIV who are also taking HAART, and even smaller for those whose HIV is suppressed.
Primary prophylaxis with trimethoprim–sulfamethoxazole may reduce the risk of PCP, and has been found to be more effective than pentamidine or dapsone.
Atovaquone may prevent PCP in people who cannot tolerate trimethoprim−sulfamethoxazole.
We don't know whether these drugs prevent toxoplasmosis as we found few RCTs, but there is consensus that standard trimethoprim–sulfamethoxazole prophylaxis or dapsone should offer adequate coverage for toxoplasmosis.
Tuberculosis can be prevented by standard primary prophylaxis in people who are tuberculin skin test positive.
Short-term combination treatment has similar efficacy to long-term isoniazid monotherapy, but is associated with a greater risk of adverse effects.
Azithromycin or clarithromycin reduce the risk of disseminated Mycobacterium avium complex (MAC) disease as primary prophylaxis for people without prior MAC disease. Adding rifabutin may also be beneficial in this population, but is also associated with an increased risk of adverse effects.
There is consensus that secondary prophylaxis with clarithromycin plus ethambutol decreases the risk of relapse in people with previous MAC disease. It remains unclear whether adding rifabutin to the dual drug regimen confers additional benefit as secondary prophylaxis, and the three-drug combination increases adverse effects.
Aciclovir as secondary prophylaxis reduces the risk of herpes simplex virus (HSV) and varicella zoster virus infection (VZV) and all-cause mortality.
Valaciclovir may reduce the risk of recurrent HSV infection, but it may be associated with serious adverse effects.
There is consensus that famciclovir is effective as secondary prophylaxis against HSV or VZV and that ganciclovir is effective as secondary prophylaxis against CMV, HSV, or VZV.
Fluconazole and itraconazole as primary prophylaxis may reduce the risk of invasive fungal infections, but azoles have been associated with potentially serious interactions with other drugs.
As secondary prophylaxis, itraconazole seems effective in reducing relapse of Penicillium marneffei, but seems less effective than fluconazole at reducing recurrence of cryptococcal meningitis.
In people who have responded to HAART and have a CD4 cell count greater than 100/mm3 to 200/mm3 (depending on the condition), discontinuation of primary or secondary prophylactic treatment for PCP, toxoplasmosis, MAC, herpes virus, or invasive fungal disease infection seems safe.
About this condition
Definition
Opportunistic infections are intercurrent infections that occur in people infected with HIV. Prophylaxis aims to avoid either the first occurrence of these infections (primary prophylaxis) or their recurrence (secondary prophylaxis, maintenance treatment). This review includes Pneumocystis jirovecii pneumonia (PCP), Toxoplasma gondii encephalitis, Mycobacterium tuberculosis, Mycobacterium avium complex (MAC) disease, cytomegalovirus (CMV) disease (most often retinitis), infections from other herpes viruses (herpes simplex virus [HSV] and varicella zoster virus [VZV]), and invasive fungal disease (Cryptococcus neoformans, Histoplasma capsulatum, and Penicillium marneffei).
Incidence/ Prevalence
The incidence of opportunistic infections is high in people with immune impairment. Data available before the introduction of highly active antiretroviral treatment (HAART) suggest that, with a CD4 count less than 250/mm3, the 2-year probability of developing an opportunistic infection is 40% for PCP, 22% for CMV, 18% for MAC, 6% for toxoplasmosis, and 5% for cryptococcal meningitis. The introduction of HAART has reduced the rate of opportunistic infections. One cohort study found that the introduction of HAART decreased the incidence of PCP by 94%, CMV by 82%, and MAC by 64%, as presenting AIDS events. HAART decreased the incidence of events subsequent to the diagnosis of AIDS by 84% for PCP, 82% for CMV, and 97% for MAC.
Aetiology/ Risk factors
Opportunistic infections are caused by a wide array of pathogens and result from immune system defects induced by HIV. The risk of developing opportunistic infections increases dramatically with progressive impairment of the immune system. Each opportunistic infection has a different threshold of immune impairment, beyond which the risk increases substantially. Opportunistic pathogens may infect the immunocompromised host de novo, but usually they are simply reactivations of latent pathogens in such hosts.
Prognosis
Prognosis depends on the type of opportunistic infection. Even with treatment they may cause serious morbidity and mortality. Most deaths due to HIV infection are caused by opportunistic infections. The absolute benefits of prophylactic regimens for opportunistic infections are probably smaller in people with HIV who are also taking HAART and even smaller for those whose HIV is suppressed. HAART has reduced the rate of PCP, toxoplasmosis, and other opportunistic infections.
Aims of intervention
To prevent the occurrence and relapse of opportunistic infections; to discontinue unnecessary prophylaxis; to minimise adverse effects of prophylaxis and loss of quality of life.
Outcomes
First occurrence of and relapse of opportunistic infections, mortality, and adverse effects of treatments. We have not considered neoplastic diseases associated with specific opportunistic infections. We have considered all-cause mortality as a secondary outcome in this review as many meta-analyses and RCTs were underpowered to detect a clinically important difference between groups in this outcome.
Methods
Clinical Evidence search and appraisal March 2008. The following databases were used to identify studies for this systematic review: Medline 1966 to March 2008, Embase 1980 to March 2008, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2008, Issue 1 (1966 to date of issue). An additional search was carried out of the NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We have not excluded "open", "open label", or not blinded trials owing to the ethical and practical difficulties of blinding trials in people with HIV. When assessing effects of primary prophylaxis for specific opportunistic infections, we have included only systematic reviews and RCTs that assessed incidence of infection; we excluded those studies that reported only on mortality without specifying that it was preceded by an opportunistic infection. When assessing invasive fungal disease, we have included only Cryptococcus neoformans, Histoplasma capsulatum, and Penicillium marneffei. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. We also reviewed abstract books/CDs for the following conferences held between 1995 and early 2001: European Clinical AIDS, HIV Drug Treatment, Interscience Conferences on Antimicrobial Agents and Chemotherapy, National Conferences on Human Retroviruses and Opportunistic Infections, and World AIDS Conference. We placed emphasis on systematic reviews and RCTs published after 1993. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see GRADE table ). The categorisation of the quality of the evidence (into high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table 1.
GRADE evaluation of interventions for HIV: primary and secondary prophylaxis for opportunistic infections
| Important outcomes | Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, tuberculosis, Mycobacterium avium complex (MAC), cytomegalovirus (CMV)/herpes simplex virus (HSV)/or varicella zoster virus (VZV), invasive fungal disease, Penicillium marneffei, cryptococcal meningitis, mortality | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of primary prophylaxis for Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis? | |||||||||
| 7 (at least 605) | PCP | Trimethoprim–sulfamethoxazole or pentamidine aerosol v placebo for primary prophylaxis against PCP | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (incomplete reporting of results, blinding). Directness point deducted for small number of events in 1 RCT (no cases of PCP) |
| 7 (at least 543) | Mortality | Trimethoprim–sulfamethoxazole or pentamidine aerosol v placebo for primary prophylaxis against PCP | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for weak methods (incomplete reporting of results, blinding) and no intention-to-treat analysis in 1 RCT |
| 14 (unclear) | PCP | Trimethoprim–sulfamethoxazole v pentamidine aerosol for primary prophylaxis against PCP | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (incomplete reporting of results, blinding). Directness point deducted for inclusion of data on secondary prophylaxis |
| 14 (unclear) | Mortality | Trimethoprim–sulfamethoxazole v pentamidine aerosol for primary prophylaxis against PCP | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (incomplete reporting of results, blinding). Directness point deducted for inclusion of data on secondary prophylaxis |
| 13 (unclear) | PCP | Trimethoprim–sulfamethoxazole v dapsone (with or without pyrimethamine) for primary prophylaxis against PCP | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for weak methods (incomplete reporting of results, blinding). Directness points deducted for inclusion of data on secondary prophylaxis and variable intervention (with or without pyrimethamine) |
| 13 (unclear) | Mortality | Trimethoprim–sulfamethoxazole v dapsone (with or without pyrimethamine) for primary prophylaxis against PCP | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for weak methods (incomplete reporting of results, blinding). Directness points deducted for inclusion of data on secondary prophylaxis and variable intervention (with or without pyrimethamine) |
| At least 2 (at least 2625) | PCP | High-dose dose trimethoprim–sulfamethoxazole v low-dose trimethoprim–sulfamethoxazole for primary prophylaxis against PCP | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of results and open-label RCT. Directness point deducted for no direct statistical analysis between groups in one review |
| 1 (2625) | Mortality | High-dose trimethoprim–sulfamethoxazole v low-dose trimethoprim–sulfamethoxazole for primary prophylaxis against PCP | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of results and open-label RCT. Directness point deducted for small number of comparators |
| 1 (545) | Toxoplasmosis | Trimethoprim–sulfamethoxazole v placebo for primary prophylaxis against toxoplasmosis | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for small number of events (7 events in total) and for restricted population |
| 1 (545) | Mortality | Trimethoprim–sulfamethoxazole v placebo for primary prophylaxis against toxoplasmosis | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for restricted population and no intention to treat analysis |
| 8 (unclear) | Toxoplasmosis | Trimethoprim–sulfamethoxazole v dapsone (with or without pyrimethamine) for primary prophylaxis against toxoplasmosis | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (incomplete reporting of results, blinding). Directness point deducted for inclusion of data on secondary prophylaxis |
| 8 (unclear) | Mortality | Trimethoprim–sulfamethoxazole v dapsone (with or without pyrimethamine) for primary prophylaxis against toxoplasmosis | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (incomplete reporting of results, blinding). Directness point deducted for inclusion of data on secondary prophylaxis |
| 1 (2625) | Toxoplasmosis | High-dose trimethoprim–sulfamethoxazole v low-dose trimethoprim–sulfamethoxazole for primary prophylaxis against toxoplasmosis | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of results and open-label RCT. Directness point deducted for small number of dose comparators |
| 1 (2625) | Mortality | High-dose trimethoprim–sulfamethoxazole v low-dose trimethoprim–sulfamethoxazole for primary prophylaxis against toxoplasmosis | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of results and open-label RCT. Directness point deducted for small number of dose comparators |
| 1 (549) | PCP | Atovaquone v pentamidine aerosol for primary prophylaxis against PCP | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for open-label RCT. Directness points deducted for restricted population (people intolerant of trimethoprim–sulfamethoxazole) and for inclusion of data on secondary prophylaxis |
| 1 (1057) | PCP | Atovaquone v dapsone for primary prophylaxis against PCP | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for open-label RCT. Directness points deducted for restricted population (people intolerant of trimethoprim–sulfamethoxazole) |
| 1 (1057) | Mortality | Atovaquone v dapsone for primary prophylaxis against PCP | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for open-label RCT. Directness points deducted for restricted population (people intolerant of trimethoprim–sulfamethoxazole) |
| What are the effects of primary antituberculosis prophylaxis in people with HIV infection? | |||||||||
| At least 13 (at least 5595) | Tuberculosis | Antituberculosis regimens v placebo for primary prophylaxis against TB | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for weak methods in some RCTs (blinding, placebo group received active treatment in 1 RCT, 1 RCT terminated early) |
| 6 (at least 5298) | Mortality | Antituberculosis regimens v placebo for primary prophylaxis against TB | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for weak methods in some RCTs (blinding, placebo group received active treatment in 1 RCT, 1 RCT terminated early, 1 RCT no intention-to-treat analysis). Consistency point deducted for inconsistent effects between population groups (adults, children) |
| 10 (5584) | Tuberculosis | Antituberculosis regimens v each other for primary prophylaxis against TB | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (unclear rates of adherence, definitions varying between RCTs). Directness point deducted for different rates of adherence between regimens affecting interpretation of results |
| 11 (5520) | Mortality | Antituberculosis regimens v each other for primary prophylaxis against TB | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (unclear rates of adherence, definitions varying between RCTs). Directness point deducted for different rates of adherence between regimens affecting interpretation of results |
| 8 (5584) | Adverse effects | Antituberculosis regimens v each other for primary prophylaxis against TB | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (unclear rates of adherence, definitions varying between RCTs). Directness point deducted for different rates of adherence between regimens affecting interpretation of results |
| What are the effects of primary prophylaxis for disseminated Mycobacterium avium complex (MAC) disease for people without previous MAC disease? | |||||||||
| 1 (174) | MAC | Azithromycin v placebo for primary prophylaxis against MAC | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for restricted population |
| 1 (174) | Mortality | Azithromycin v placebo for primary prophylaxis against MAC | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for restricted population |
| 1 (667) | MAC | Clarithromycin v placebo for primary prophylaxis against MAC | 4 | 0 | 0 | –1 | +1 | High | Directness point deducted for restricted population (advanced AIDS). Effect-size point added for HR less than 0.5 |
| 1 (667) | Mortality | Clarithromycin v placebo for primary prophylaxis against MAC | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for restricted population (advanced AIDS) |
| 1 (1178) | MAC | Clarithromycin plus rifabutin v clarithromycin alone or v rifabutin alone primary prophylaxis against MAC | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (1178) | Mortality | Clarithromycin plus rifabutin v clarithromycin alone or v rifabutin alone primary prophylaxis against MAC | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (1178) | Adverse effects | Clarithromycin plus rifabutin v clarithromycin alone or v rifabutin alone primary prophylaxis against MAC | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for no direct statistical analysis between individual groups for overall adverse effects or uveitis |
| 1 (693) | MAC | Azithromycin plus rifabutin v azithromycin alone or v rifabutin alone for primary prophylaxis against MAC | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (693) | Mortality | Azithromycin plus rifabutin v azithromycin alone or v rifabutin alone for primary prophylaxis against MAC | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for no direct statistical analysis between groups |
| 1 (unclear) | Adverse effects | Azithromycin plus rifabutin v azithromycin alone or v rifabutin alone primary prophylaxis against MAC | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and for unclear outcome |
| What are the effects of secondary prophylaxis for disseminated Mycobacterium avium complex (MAC) disease for people with previous MAC disease? | |||||||||
| 1 (160) | MAC | Clarithromycin plus ethambutol v clarithromycin plus ethambutol plus rifabutin for secondary prophylaxis against MAC | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, open-label RCT, and incomplete reporting of results |
| 1 (160) | Mortality | Clarithromycin plus ethambutol v clarithromycin plus ethambutol plus rifabutin for secondary prophylaxis against MAC | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, open-label RCT, and incomplete reporting of results |
| What are the effects of secondary prophylaxis for cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV)? | |||||||||
| 1 (unclear) | Herpes simplex virus (HSV), varicella zoster virus (VZV) | Aciclovir v valaciclovir for secondary prophylaxis against HSV or VZV | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (293) | Herpes simplex virus (HSV), varicella zoster virus (VZV) | Valaciclovir v placebo for secondary prophylaxis against CMV, HSV, VZV | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (unclear) | Herpes simplex virus (HSV), varicella zoster virus (VZV) | Different valaciclovir dosage schedules v each other for secondary prophylaxis against CMV, HSV, VZV | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (48) | Herpes simplex virus (HSV), varicella zoster virus (VZV) | Famciclovir v placebo for secondary prophylaxis against CMV, HSV, VZV | 4 | –3 | 0 | –2 | 0 | Very low | Quality points deducted for sparse data, high withdrawal rate, and analysis by number of days with symptoms rather than by randomised groups. Directness point deducted for surrogate non-clinical outcome and inclusion of people with recurrent HSV |
| What are the effects of primary prophylaxis for invasive fungal disease in people without previous fungal disease? | |||||||||
| 1 (90) | Invasive fungal disease | Fluconazole v placebo for primary prophylaxis against invasive fungal disease | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for sparse data. Directness points deducted for small number of events (10 in total) and restricted population |
| 1 (90) | Mortality | Fluconazole v placebo for primary prophylaxis against invasive fungal disease | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for sparse data. Directness points deducted for small number of events (10 in total) and restricted population |
| 3 (808) | Invasive fungal disease | Itraconazole v placebo for primary prophylaxis against invasive fungal disease | 4 | 0 | 0 | 0 | +2 | High | Effect-size points added for RR less than 0.2 |
| 3 (808) | Mortality | Itraconazole v placebo for primary prophylaxis against invasive fungal disease | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (636) | Invasive fungal disease | High-dose fluconazole v low-dose fluconazole for primary prophylaxis against invasive fungal disease | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for small number of comparators |
| 1 (636) | Mortality | High-dose fluconazole v low-dose fluconazole for primary prophylaxis against invasive fungal disease | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for small number of comparators |
| 1 (428) | Invasive fungal disease | Fluconazole v clotrimazole troches for primary prophylaxis against invasive fungal disease | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for open-label RCT. Directness point deducted for restricted population |
| 1 (428) | Mortality | Fluconazole v clotrimazole troches for primary prophylaxis against invasive fungal disease | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for open-label RCT. Directness point deducted for restricted population |
| What are the effects of secondary prophylaxis for invasive fungal disease in people with previous invasive fungal disease? | |||||||||
| 1 (71) | Penicillium marneffei | Itraconazole v placebo for secondary prophylaxis against invasive fungal disease | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (71) | Mortality | Itraconazole v placebo for secondary prophylaxis against invasive fungal disease | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (108) | Cryptococcal meningitis | Itraconazole v fluconazole for secondary prophylaxis against invasive fungal disease | 4 | –1 | 0 | –1 | +2 | High | Quality point deducted for sparse data. Effect-size points added for RR less than 0.2. Directness point deducted for small number of events |
| 1 (108) | Mortality | Itraconazole v fluconazole for secondary prophylaxis against invasive fungal disease | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for small number of events |
| What are the effects of discontinuing primary prophylaxis against opportunistic pathogens in people on highly active antiretroviral treatment (HAART)? | |||||||||
| 1 (474) | Pneumocystis jirovecii pneumonia (PCP) | Discontinuation v continuation of primary prophylaxis for PCP | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for open-label RCT |
| 2 (at least 381) | Toxoplasmosis | Discontinuation v continuation of primary prophylaxis for toxoplasmosis | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for open-label RCT and for incomplete reporting of results |
| 2 (1163) | Mycobacterium avium complex (MAC) | Discontinuation v continuation of primary prophylaxis for MAC | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for small number of comparators (azithromycin only) |
| What are the effects of discontinuing secondary prophylaxis against opportunistic pathogens in people on highly active antiretroviral treatment (HAART)? | |||||||||
| 2 (259) | Pneumocystis jirovecii pneumonia (PCP) | Discontinuation v continuation of secondary prophylaxis for PCP | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for open-label RCTs |
| 1 (57) | Toxoplasmosis | Discontinuation v continuation of secondary prophylaxis for toxoplasmosis | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and open-label RCT |
| 1 (42) | Invasive fungal disease | Discontinuation v continuation of secondary prophylaxis for invasive fungal disease | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for small number of comparators (cryptococcus only) |
Type of evidence: 4 = RCT Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio
Glossary
- High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Penicillium marneffei infection
A common opportunistic infection in South East Asia.
- Very low-quality evidence
Any estimate of effect is very uncertain.
- WHO staging system
for HIV infection and disease consists of a “clinical axis” that is represented by a sequential list of clinical conditions believed to have prognostic significance, which subdivides the course of HIV infection into four clinical stages; and a “laboratory axis” that subdivides each clinical stage into three strata according to CD4 cell count or total lymphocyte count.
Antiretroviral regimens (see review on HIV infection)
Treating P jirovecii pneumonia in people with HIV
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Judith Aberg, Director of Virology, Bellevue Hospital Center, New York University School of Medicine, New York, USA.
William Powderly, Dean, UCD School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
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