Morbidity in HIV-1-infected individuals before and after the introduction of antiretroviral therapy: a longitudinal study of a population-based cohort in Uganda.
ABSTRACT We compared morbidities in HIV-1-infected patients before and after the introduction of antiretroviral therapy (ART) in a rural Ugandan cohort followed from 1990 to 2008. ART was introduced in 2004.
Random-effects Poisson regression models were used to estimate incidence rates of World Health Organization (WHO) stage-defining diseases in HIV-infected individuals aged 13 years or older with known seroconversion dates, and in an age-stratified sample of HIV-negative individuals.
The most common morbid event was bacterial pneumonia, with an incidence of 7.4/100 person-years (pyr) among 309 HIV seroconverters and 1.3/100 pyr among 348 HIV-negative participants [hazard ratio (HR) 5.64; 95% confidence interval (CI) 3.6-8.8]. Among seroconverters, the incidence of the acquisition of any WHO stage-defining disease rose from 14.4/100 pyr (95% CI 11.1-18.6) in 1990-1998 to 46.0/100 pyr (95% CI 37.7-56.0) in 1999-2003. Following the introduction of ART, the incidence among seroconverters declined to 36.4/100 pyr (95% CI 27.1-48.9) in 2004-2005 and to 28.3/100 pyr (95% CI 21.2-37.8) in 2006-2008. At the individual level, a higher rate of acquiring any WHO stage-defining disease was independently associated with lower CD4 cell count, longer duration of HIV infection and older age. In addition, individuals who had been on ART for longer than 12 months had a substantially lower rate of any WHO stage disease than those not yet on ART (adjusted HR 0.35; 95% CI 0.2-0.6).
Morbidity in HIV-positive participants decreased following the introduction of ART, and this decline was more marked with increasing duration on ART. The benefits of decreased HIV-related morbidity from ART lend support to urgent efforts to ensure universal access to early diagnosis of HIV infection and to ART, especially in rural Africa.
- [show abstract] [hide abstract]
ABSTRACT: To determine the incidence of HIV-1 infection and HIV-1-associated mortality in a rural Ugandan population. A prospective cohort study. A cohort consisting of the population (de jure census 9820) of a cluster of 15 villages in Masaka District, south-west Uganda was enrolled between 1989 and 1990 through a demographic and medical survey. The HIV-1 seroprevalence rate was 4.8% for all ages combined and 8.2% for those aged 13 years or more. The survey was repeated after 1 year. The 1-year HIV-1 incidence rate among adults was 1% [9.2 per 1000 person-years of observation; 95% confidence interval (CI), 5.5-12.9). A total of 84 deaths were observed. In adults, half of all deaths (31 out of 60) were in HIV-1-seropositive individuals. The age-adjusted overall mortality rate ratio for HIV-positive adults compared with HIV-negatives was 20.8 (95% CI, 12.0-35.7). In the 13-44 age group the corresponding rate ratios for men, women and both sexes combined were 16.3, 108.9 and 58.7, respectively. The HIV-attributable mortality fractions, i.e., the proportion of deaths that would have been avoided in the absence of HIV, were 44, 50 and 89% for adult men, adult women and adults aged 25-34 years (both sexes combined), respectively. The 1-year progression to death among HIV-1-seropositive adults was 10.3%. These results demonstrate the profound impact that the HIV-1 epidemic has on adult mortality in a rural area of Uganda where the HIV-1 prevalence and incidence rates in adults are 8 and 1%, respectively.AIDS 02/1994; 8(1):87-92. · 6.41 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid. The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.New England Journal of Medicine 03/1998; 338(13):853-60. · 51.66 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The use of protease inhibitor-containing (PI) combination antiretroviral therapy has led to a reduction in the incidence of opportunistic illness and mortality (events) in HIV infection. We wished to quantify the changing incidence of these events in our clinical practice and delineate the relationship between CD4, HIV-1 RNA, and development of events in patients receiving PI combination therapy. We assessed HIV-infected patients with CD4 counts < or =500 cells x10(6)/l. We calculated the incidence of events from 1994 through 1998 and analyzed the association of temporal changes in event incidence and use of antiretroviral therapy. In patients on PI combination therapy, we determined the probability of achieving and maintaining an undetectable HIV-1 RNA response and determined the association of CD4, HIV-1 RNA, and developing an event. The incidence of opportunistic illness declined from 23.7 events/100 person-years in 1994 to 14.0 events/100 person-years in 1998 (P<0.001). Mortality declined from 20.2 deaths/100 person-years in 1994 to 8.4 deaths/ 100 person-years in 1998 (P<0.001). Use of PI combination therapy was associated with a relative rate of opportunistic illness or death of 0.66 [95% confidence interval (CI), 0.51-0.85; P<0.001]. The relative incidence of each of 16 opportunistic illnesses was approximately the same in 1998 as in 1994 except for lymphoma, cervical cancer and wasting syndrome which do not appeared to have declined in incidence. Approximately 60% of patients who received PI therapy achieved an undetectable HIV-1 RNA, and 65% of these patients maintained durable suppression of HIV-1 RNA. Achieving an undetectable HIV-1 RNA was associated with a decreased risk of an event, and was the variable most strongly associated with an increase in CD4 level. By multivariate analysis, the concurrent CD4 level was most strongly associated with developing an event. We observed a significant decline in the incidence of opportunistic illness and death from 1994 through 1998 associated with combination antiretroviral therapy. Patients who develop events while being treated with PI combination therapy were not likely to have achieved an undetectable HIV-1 RNA and are likely to have a low concurrent CD4 level.AIDS 11/1999; 13(14):1933-42. · 6.41 Impact Factor