This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

BACKGROUND The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

/pdf/effect-of-early-versus-deferred-antiretroviral-therapy-for-151y3faw0v.pdf

Effect of early versus deferred antiretroviral therapy for HIV on survival.

BACKGROUND
Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy.


METHODS
The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, and stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude mortality rates were also calculated.


FINDINGS
18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, respectively. 2056 (4.7%) deaths were observed during the study period, with crude mortality rates decreasing from 16.3 deaths per 1000 person-years in 1996-99 to 10.0 deaths per 1000 person-years in 2003-05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36.1 (SE 0.6) years to 49.4 (0.5) years. Women had higher life expectancies than did men. Patients with presumed transmission via injecting drug use had lower life expectancies than did those from other transmission groups (32.6 [1.1] years vs 44.7 [0.3] years in 2003-05). Life expectancy was lower in patients with lower baseline CD4 cell counts than in those with higher baseline counts (32.4 [1.1] years for CD4 cell counts below 100 cells per muL vs 50.4 [0.4] years for counts of 200 cells per muL or more).


INTERPRETATION
Life expectancy in HIV-infected patients treated with combination antiretroviral therapy increased between 1996 and 2005, although there is considerable variability between subgroups of patients. The average number of years remaining to be lived at age 20 years was about two-thirds of that in the general population in these countries.

Antiretroviral therapy cohort collaboration : life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

Unselected patients in whom highly active antiretroviral therapy is started in a clinic setting achieve viral suppression substantially less frequently than do patients in controlled clinical trial...

Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions.

Context.—Time to development of acquired immunodeficiency syndrome (AIDS) and
time to death have been extended with the increased use of combination therapy
and protease inhibitors. Cohort studies following up persons with human immunodeficiency
virus (HIV) infection in periods characterized by different therapies offer
the opportunity to estimate therapy effectiveness at the population level.Objective.—To assess the effectiveness of self-reported, long-term potent antiretroviral
therapy in a cohort of 536 men whose duration of HIV infection was known (seroconverters).Design.—Cohort study. The cohort was compared for time to development of AIDS
and time to death in 1984 to 1990, 1990 to 1993, 1993 to July 1995, and July
1995 to July 1997 when the major treatments were no therapy, monotherapy,
combined therapy, and potent antiretroviral therapy, respectively. Survival
analysis methods with time zero set as the date of seroconversion and incorporating
staggered entries into each period were used. Mean CD4 cell change, stratified
by infection duration, was determined for each period using a random effects
model.Setting.—The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore,
Md; Chicago, Ill; Los Angeles, Calif; and Pittsburgh, Pa).Participants.—A total of 5622 men who were 18 years or older were enrolled into MACS.
Of the 5622, there were 2191 HIV-positive individuals at enrollment. Of the
3431 men who were HIV-negative, 536 were observed to seroconvert and were
followed up for up to 13 years. The group of 536 who seroconverted constituted
the study population.Main Outcome Measures.—Time from seroconversion to development of AIDS and to death and change
in CD4 cell count.Results.—A total of 231 seroconverters developed AIDS, and 200 men died. Using
1990 to 1993 as the reference period, the relative hazard of AIDS was 1.04
(95% confidence interval [CI], 0.73-1.48) during 1993 to July 1995 and 0.35
(95% CI, 0.20-0.61) during July 1995 to July 1997. Relative hazards of death
were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% CI, 0.38-1.01) for the same periods.
The relative time (the factor by which times are contracted or expanded) to
development of AIDS was 0.97 (95% CI, 0.86-1.09) for 1993 to July 1995 and
1.63 (95% CI, 1.40-1.89) for July 1995 to July 1997. Relative survival time
for 1993 to July 1995 was 1.01 (95% CI, 0.91-1.12) and for July 1995 to July
1997 was 1.21 (95% CI, 1.07-1.36) relative to 1990 to 1993. The rate of CD4
cell count decline in July 1995 to July 1997 was significantly lower (P<.05) compared with the previous 2 periods.Conclusions.—In the calendar period when potent antiretroviral therapy was introduced,
the time to development of AIDS and time to death were extended, and rate
of CD4 cell count decline was arrested.

/pdf/effectiveness-of-potent-antiretroviral-therapy-on-time-to-miouz6hssp.pdf

Effectiveness of Potent Antiretroviral Therapy on Time to AIDS and Death in Men With Known HIV Infection Duration

Non-Hodgkin’s lymphoma (NHL) has been increasing in frequency in the industrialized world, but the environmental and genetic factors that contribute to susceptibility are not known. B-cell lymphomas represent a major cause of morbidity and mortality in HIV-infected individuals. The identification of a deletion in the CCR5 chemokine receptor gene that alters the risk for infection and progression to AIDS led us to examine a potential role of this gene in AIDS lymphoma. A matched case-control analysis was performed using all eligible NHL cases in the Multicenter AIDS Cohort Study. Patients were matched for age, study center, time AIDS-free, and slope of the CD4+ T-cell decline. The CCR5-Δ32 allele was found to be associated with a 3-fold lower risk of NHL among individuals after controlling for time of infection and progression toward AIDS. The CCR5 gene was not associated with a difference in risk for Kaposi’s sarcoma, another common malignancy in AIDS patients, or opportunistic infections. Costimulation of normal phorbol 12-myristate 13-acetate-treated B cells with the CCR5 ligand RANTES induced a proliferative response, indicating that RANTES is a mitogen for B cells. Taken together, these findings suggest that the CCR5 gene plays a role in the risk of NHL in HIV-infected patients, perhaps through a mechanism involving a decreased response of B cells to the mitogenic activity of RANTES.

https://cancerres.aacrjournals.org/content/canres/59/15/3561.full.pdf

Reduced Risk of AIDS Lymphoma in Individuals Heterozygous for the CCR5-Δ32 Mutation

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Effectiveness of Potent Antiretroviral Therapy on Time to AIDS and Death in Men With Known HIV Infection Duration

Reduced Risk of AIDS Lymphoma in Individuals Heterozygous for the CCR5-Δ32 Mutation