pre-AIDS Mortality Research Articles

Natural history of HIV infections among injecting drug users in Dehong prefecture, Yunnan province

To study the natural history of HIV-1 infection among intravenous drug users (IDUs) detected in late 1989 in the study area and the factors related to survival of these IDUs infected with HIV. 196 injecting drug users first detected during August and December, 1989 were observed in Ruili county, Yunnan province. Data gathered from the 20-year follow-up program was collected and analyzed retrospectively. After 20 years' follow-up period, 90.3% of the 196 IDUs with HIV infection died, 5.1% of them were still alive, and 4.6% were lost. The crude pre-AIDS mortality rate was 98.1/1000 person-years, and the AIDS mortality rate was 54.9/1000 person-years. Malaria, septicemia were the main causes of death among the natural diseases whereas overdose and accidental causes were the principal causes related to those non-disease deaths. The median survival time from sero-conversion to death was 8.6 years (95%CI: 7.6 - 9.7). The median survival time from sero-conversion to death due to AIDS was 11.3 years (95%CI: 10.3 - 12.8) with the incubation time as around 10.3 years. People older than 30 years at seroconversion and length of drug usage were associated with shorter survival time, with hazards ratios as 1.9 and 0.7, respectively. A high pre-AIDS mortality was observed among IDUs. Both the median survival time from sero-conversion to death and the HIV incubation period were shorter than that observed in the developed countries. Age of HIV infection seemed to have a strong effect on survival.

HIV prevalence for New York State using Newborn Seroprevalence and AIDS Surveillance Data

The objective of this work is to estimate human immunodeficiency virus (HIV) prevalence in the adult populations of New York City, and of New York State (NYS) excluding New York City. Evidence is presented that not all HIV-infected persons live long enough to satisfy an acquired immunodeficiency syndrome (AIDS) diagnosis. The term preAIDS mortality refers to the mortality of HIV-infected persons, due to any cause, before they can be diagnosed with AIDS. The effect of preAIDS mortality on the estimate of HIV incidence, using back calculation of AIDS Surveillance Data, is to produce low-biased estimates of HIV incidence and prevalence. Estimates of HIV prevalence in women of childbearing age were obtained from the Newborn Seroprevalence Survey [Lessner L. The estimation of HIV prevalence for women of childbearing age in New York City, presently under review]. HIV-positive women in this population typically do not have an opportunistic infection. Thus estimates of HIV prevalence in this population occurred earlier in the spectrum of HIV disease then when they finally satisfied the definition of AIDS that depends on incidence of an opportunistic disease. These earlier estimates of HIV prevalence in women were found to be substantially larger then those obtained from back calculation using female AIDS Surveillance Data. This comparison was used to obtain a quantitative measure R of the effect of preAIDS mortality on HIV prevalence: where 1/ R equals the proportion of HIV-infected intravenous drug users that become AIDS cases The preAIDS mortality adjustment factor R was used in the estimation of HIV prevalence and incidence for NYS. We believe that the use of the adjustment factor resulted in more accurate estimates. Using this factor, our estimated HIV incidence for New York City in 1991 was nearly 26% larger than without the adjustment while projected HIV prevalence for 1996 was nearly 27% larger. The paper estimates HIV prevalence. The AIDS Surveillance operation uses AIDS cases to back calculate HIV incidence and prevalence. Since many HIV-infected intravenous drug using (IDU) population die before they become an AIDS case, the estimates from the back calculation are low biased. Low biased because there were many HIV-infected people who died before they ever satisfied the AIDS protocol. The totals presented here adjust for preAIDS mortality and are necessarily larger than what was recorded by the NYS Dept. of Health. After the change in the definition of AIDS to simply HIV prevalence and the change to electronic reporting, the totals were mostly HIV cases reported in the given year and not AIDS. Thus there is no comparison. This paper represents the last best look at the natural history of AIDS in NYS.

Including pre-AIDS mortality in back-calculation model to estimate HIV prevalence in France, 2000

Since the advent of highly active antiretroviral therapy (HAART) the lengthening of AIDS incubation time has led to a decrease of AIDS incidence and mortality, and to the increase of the proportion of pre-AIDS mortality. The objective was to develop an extension of the back-calculation model by including pre-AIDS mortality and to estimate HIV prevalence in France. Our previous back-calculation model was modified to take into account the probability of survival for HIV-infected individual using the relative risk to die at different period for an HIV-infected person versus the general population (psi). AIDS cases reported to InVS (Institut de Veille Sanitaire) until March 2003 were back-calculated to estimate HIV incidence until December 2000. AIDS deaths occurring until December 2000 were used to obtain HIV prevalence in 2000. Plausible intervals were calculated taking into account uncertainties on AIDS incubation time. Taking into account pre-AIDS mortality increased the goodness-of-fit of the model to the data. The relative risk, psi, was estimated as 3 for homo-bisexual men, haemophiliacs and transfused cases, 10 for intravenous drug users, and 4 for heterosexual cases, with no difference over period. HIV prevalence in 2000 was estimated as 88,200 (with a plausible interval of 52,300-168,000), versus 78,200 when mortality was not considered. Pre-AIDS mortality estimates show the amount of this mortality during the era of HAART but also evidenced its existence before HAART. Taking into account pre-AIDS mortality of HIV-infected person in the back-calculation model increased the estimated HIV prevalence.

Estimation of AIDS adult mortality by verbal autopsy in rural Malawi.

To estimate AIDS-related adult mortality using verbal autopsies (VA) in a rural sub-Saharan African setting with high HIV prevalence. VA data were collected from relatives and neighbors that described the circumstances leading to death for 92 adults in three rural areas of Malawi. These adults were initially interviewed in 1998 as part of a longitudinal social survey of a sample of 1554 women and 1126 men, and their deaths occurred between then and a 3-year follow-up interview in 2001. AIDS-related deaths were identified using a standard World Health Organization (WHO) algorithm and this observed number of deaths was compared with the expected number. The expected number is derived from a comparison of adult mortality in this sample with the pre-AIDS mortality levels measured in the 1987 Malawi census, giving an 'excess mortality factor' that can be considered to be AIDS related. It was calculated that 74.9% of observed deaths in 1998-2001 would be from AIDS. According to the WHO algorithm, 75.5% of the VA deaths could be categorized as AIDS deaths. The gender-specific figures were 75.1% for females and 76.3% for males. Results are consistent with those found in studies conducted in other areas of sub-Saharan Africa at earlier stages in the epidemic. They confirm that VA data can be used to estimate with a reasonable degree of confidence the distribution of AIDS- and non-AIDS-related deaths in the aggregate, even in a rural population with relatively low levels of education.

Anonymous reporting of HIV infection: an evaluation of the HIV/AIDS surveillance system in Norway 1983-2000.

Several European countries are considering implementing surveillance systems for HIV infection, but questions remain regarding patient confidentiality. The population-based HIV/AIDS surveillance system in Norway integrates anonymous HIV case reports from laboratories and clinicians and named AIDS case reports. This evaluation includes a description of the system, evidence of system attributes, estimation of resources for system operations, and documentation of the system's usefulness. HIV case reports provide a far better picture of the epidemic than AIDS reports. The median delay between positive HIV test and reporting was 30 days (interquartile range 18-49 days). Completeness of demographic and epidemiologic information in the surveillance database ranges from 60 to 100%. Information on pre-AIDS mortality and emigration is incomplete. The system cost euro 25,200 in 1999. Results are published every week and used for planning of health care and prevention. We conclude that the Norwegian surveillance system with anonymous reporting of HIV cases is simple, inexpensive and flexible, and capable of providing a representative and timely overview that guides prevention. The system fulfils its objectives while respecting confidentiality and adhering to ethical principles. A similar system may be considered in other countries.

Pre-AIDS mortality and its association with HIV disease progression in haemophilic men, injecting drug users and homosexual men.

To study pre-AIDS mortality and its association with HIV disease progression in different exposure groups with known intervals of HIV seroconversion. The type and rate of pre-AIDS deaths were assessed in 111 HIV-infected haemophilic men followed in London, and 118 injecting drug users and 158 homosexual men followed in Amsterdam. In each group, the association between CD4+ T-cell count, HIV RNA and pre-AIDS mortality was studied using proportional hazards analysis. By 10 years after seroconversion 7.3% of the haemophilic men had died without AIDS and 38.2% had developed AIDS. These figures were 20.2 and 30.5% for injecting drug users, and 8.0 and 55.0% for homosexual men. The major causes of pre-AIDS mortality appear to differ in the three exposure groups. The risk of pre-AIDS death tended to increase with decreasing CD4 cell count and increasing HIV RNA levels in injecting drug users and homosexual men. In men with haemophilia the associations were less obvious, although the log-transformed CD4 cell count was predictive for pre-AIDS death. Pre-AIDS deaths occur and are at least partially related to HIV disease progression irrespective of how individuals became infected. Because of the longer life expectancy due to highly active antiretroviral therapy (HAART), pre-AIDS deaths are likely to show a further increase. Methods to incorporate these intermediate outcomes should be considered in the estimation of the size of the HIV epidemic and in the survival analysis of HIV-infected individuals. Prevention and treatment of non-AIDS infections, especially hepatitis C virus infection, and cancers will become increasingly important in HIV-infected individuals. The interaction between these therapies and HAART should be closely monitored.

Some aspects of the natural history of HIV infection.

Studying factors influencing the length of the incubation period of HIV/AIDS is important to our understanding of the natural history of the disease and for the decision when to start with anti-retroviral therapy. In a multicentre study among HIV-positive homosexual men with a known date of seroconversion, we found that the median survival time after HIV infection was 12.1 years. Age is an important determinant of the survival: the older the shorter the incubation period and survival. Gender does not seem to play a role, but women appear to have higher CD4 counts than men at seroconversion, AIDS and death. HIV-positive drug users often die before they 'reach' AIDS often from HIV-related causes e.g. bacterial infections. In a multicentre study we found that such pre-AIDS mortality is now also found among homosexual men and haemophiliacs but at a much lower level. Most studies show that HIV subtype does not influence the incubation period. On the other hand genetic factors do play an important role.

Geographical variation in disease progression in HIV-1 seroconverted injecting drug users in Europe?

Human immunodeficiency virus (HIV) disease progression might vary by geographical region due to differences in the spectrum of HIV-related illnesses and (access to) health care. Therefore, the effect of geographical region, next to the effect of other potential cofactors, on disease progression in 664 injecting drug users (IDU) with documented HIV seroconversion from eight cohorts in Europe was studied. Kaplan-Meier methods and Cox proportional hazards analysis were performed to assess the effect of geographical region, other sociodemographics, drug use and repeated HIV exposure on progression from HIV seroconversion to immunosuppression, AIDS and death with AIDS. We considered the confounding effect of study-design related factors (e.g. setting of follow-up), and accounted for pre-AIDS death from natural causes by imputing when each endpoint would have occurred, had they not died without AIDS. Estimates of progression to AIDS and death with AIDS were substantially faster after taking pre-AIDS mortality into account. Median incubation time from seroconversion to the first CD4 count < 200 cells/microliter was 7.7 years (95% CI: 7.1-8.3) and to AIDS 10.4 years (95% CI: 9.8-infinity). The 10-year survival was 70.3% (95% CI: 62.8-76.6). The relative hazards (RH) of AIDS for IDU from central and southern Europe compared with IDU from northern Europe was 1.9 (95% CI: 1.2-3.0) and 1.2 (95% CI: 0.6-2.3), respectively, before, and 1.5 (95% CI: 0.7-3.2) and 1.1 (95% CI: 0.6-2.3) after taking differences in study-design related factors into account. Accounting for these factors, the RH of death with AIDS was 0.9 (95% CI: 0.3-2.5) for central and 1.2 (95% CI: 0.4-3.4) for southern Europe compared with northern Europe. For the first CD4 count < 200 cells/microliter these figures were 0.8 (95% CI: 0.5-1.4) and 0.8 (95% CI: 0.5-1.4). Age at seroconversion was the strongest predictor of disease progression. No statistically significant differences in disease progression were found by gender, foreign nationality, drug use and potential repeated HIV exposure. We found no evidence for regional variability in HIV disease progression among European IDU. Future studies evaluating geographical differences should consider the confounding effect of study-design related factors and differential non-AIDS mortality. As age is an important determinant of disease progression, it should be considered in recommending treatment.

Pre-AIDS Mortality and Morbidity among Injection Drug Users in Amsterdam and Baltimore: An Ecological Comparison

Mortality and morbidity between injecting drug users in Amsterdam (n= 624) and Baltimore (n = 2,185) are compared to generate a hypothesis about the role of different health care systems and drug user policies (universal care and harm reduction versus episodic care and criminalization, respectively). Overdose/suicide mortality was twofold higher in Amsterdam; no sufficient explanation was found. Other independent “risk factors” for overdose/suicide mortality were recent injecting, polydrug use, and HIV-seropositivity (especially with CD4 count < 200/mm3). High dose methadone maintenance was associated with lower mortality. Incidence of hospitalizations and emergency room visits was substantially lower in Amsterdam, suggesting that higher accessibility to primary care in Amsterdam lowers (inpatient) hospital visits and presumably societal costs.

Tiempo libre de SIDA y supervivencia de una cohorte de usuarios de drogas por vía parenteral seroconvertores frente al VIH

To analyze AIDS free time, survival and the pre-AIDS survival for a injecting drug users cohort (IDU) of HIV seroconvertors. Interval for seroconversion was available for 276 IDUs from Centers for AIDS Information and Prevention (CIPS) recruited between 1987 and until June of 1996. AIDS diagnosis and vital status dates were obtained by follow up at hospitals, mortality and AIDS registries, and CIPS visits. The end of follow up was December of 1996. Seroconversion date was estimated as the middle point between last HIV- and first HIV+. Kaplan-Meier extension and Cox regression for truncated data were fitted to estimate AIDS-free and survival times and to observe differences by sex, age consumption time and year of seroconversion. Weibull, and Log-normal parametric models were fitted to estimate median and percentiles of AIDS-free and survival times distribution. 34 cases have been identified as AIDS, 24 as deaths, 9 of them being before AIDS. 63.5% of the individuals were AIDS-free 7 years after seroconversion, and the probability of death was 25.50. Pre-AIDS mortality is around 8.7%. There were not significant differences by sex, age, consumption time and year of seroconversion. Log-normal model fitted better estimating an AIDS-free median time of 10.93 years and 13.67 survival years. The incubation period of HIV infection in a cohort of seroconvertors in our environment was around 11 years, not different from that observed out of the Mediterranean area as Holland, Scotland or United States

Pre-AIDS mortality in HIV-infected individuals in England, Wales and Northern Ireland, 1982-1996.

To assess pre-AIDS mortality in HIV-infected patients in England, Wales and Northern Ireland during the period 1982-1996. Surveillance data on pre-AIDS and AIDS deaths reported to the PHLS-AIDS Centre were analysed. Pre-AIDS mortality was estimated as the proportion of pre-AIDS deaths among all deaths in HIV-infected people. Trends over time in the number of pre-AIDS and AIDS deaths were compared using Poisson regression with logarithmic link. Causes of pre-AIDS deaths were recorded. Comparisons were made between the pre-AIDS and the AIDS death groups by logistic regression for: age, location of residence at death, year of death and risk exposure. Four-hundred and sixty-eight pre-AIDS deaths and 8574 AIDS deaths were identified. Pre-AIDS mortality accounted for 5.0% of HIV-related deaths. Trends over time in the number of pre-AIDS and AIDS deaths were not significantly different (P=0.11). Reported causes of pre-AIDS death included pneumonia (92), liver disease (62), septicaemia (51), malignancies (49), suicide (45), cardiopulmonary causes (46), haemorrhage (42), overdose (24) and accidental causes (24). Factors positively associated with pre-AIDS death were injecting drug use, haemophilia and blood transfusion, residence outside the Thames regions, and death at an older age. Pre-AIDS mortality represents a substantial proportion of HIV mortality, particularly where injecting drug use is a frequent route of HIV transmission.

Pre-AIDS mortality in the Edinburgh City Hospital HIV Cohort

Pre-AIDS mortality in the Edinburgh City Hospital HIV Cohort

Pre-AIDS mortality in the Edinburgh City Hospital HIV Cohort

Pre-AIDS mortality in the Edinburgh City Hospital HIV Cohort

Pre-AIDS mortality from natural causes associated with HIV disease progression: evidence from the European Seroconverter Study among injecting drug users.

To study differences in pre-AIDS mortality between European cohorts of injecting drug users (IDU) and to evaluate whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count. The study population consisted of 664 IDU with documented intervals of HIV seroconversion from eight cohort studies. Differences in pre-AIDS mortality were studied between European sites; an evaluation of whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count was carried out using Poisson regression. One hundred and seven IDU died, of whom 57 did not have AIDS. Pre-AIDS causes of death were overdose/suicide (49%), natural causes such as bacterial infections/cirrhosis (40%), and unintentional injuries/unknown (11%). Considering pre-AIDS death and AIDS as competing risks, 14.7% were expected to have died without AIDS and 17.3% to have developed AIDS at 7 years from seroconversion. No statistically significant differences in pre-AIDS mortality were found between European regions, men and women, age categories and calendar time periods. Overall pre-AIDS mortality did not increase with time since seroconversion, but did increase with decreasing CD4 count. Evaluating cause-specific mortality, only pre-AIDS mortality from natural causes appeared to be associated with time since seroconversion as well as immunosuppression. For natural causes, the death rate per 100 person-years was 0.13 the first 2 years after seroconversion, 0.73 in years 2-4 [risk relative (RR) to years 0-2, 5.6], 1.83 in years 4-6 (RR, 14.0) and 1.54 for > or = 6 years (RR, 11.7). This rate was 0 for a CD4 cell count > or = 500 x 10(6)/l, 1.06 for 200-500 x 10(6)/l and 4.06 for < 200 x 10(6)/l (RR versus > or = 200 x 10(6)/l, 7.0). In multivariate analysis, both CD4 count and time since seroconversion appeared to be independently associated with death from natural causes; CD4 count appeared to be the strongest predictor (adjusted RR, 5.9). A high pre-AIDS mortality rate was observed among IDU. No significant differences were observed across European sites. Pre-AIDS mortality from natural causes but not from overdose and suicide was associated with HIV disease progression.

The effect of the 1993 European revision of the AIDS case definition in Italy: implications for modelling the HIV epidemic.

To evaluate the effect of the 1993 European AIDS definition on reducing pre-AIDS mortality and to what degree an earlier diagnosis can be made. Prospective observational study. All patients diagnosed between January 1993 and December 1994 and reported to the National AIDS Registry from four Italian regions, who met only the new criteria for the 1993 case definition (AIDS-1993) were studied. Follow-up of patients who did not eventually meet the 1987 definition (AIDS-1987), or had not died from other causes (pre-AIDS-1987 death), was censored at the last available clinical visit before 1 April 1996. We analysed the data using Kaplan-Meier non-parametric survival analysis and Cox proportional hazards model. A total of 74 (4.1%) individuals met only the new criteria. Of these, 49 (62.2%) were men, 42 (56.8%) had pulmonary tuberculosis, 22 (29.7%) had recurrent bacterial pneumonia, and 10 (13.5%) had cervical cancer. During follow-up, 35 (45.3%) individuals developed an AIDS-1987 disease, and 10 (13.5%) died without fulfilling the AIDS-1987 definition. Pre-AIDS-1987 death accounted for 22.2% (10 out of 45) of the subsequent outcomes observed prior to 1 April 1996. Using Kaplan-Meier technique, we estimated that after 9.8 months 50% of these individuals were diagnosed with AIDS-1987 disease, or died without such a diagnosis. Individuals with lower CD4+ count at the time of the AIDS-1993 diagnosis progressed more rapidly to AIDS-1987 than those with a higher count. In contrast, pre-AIDS-1987 mortality was strongly associated with injecting drug use, whereas no association was found with CD4+ count. Approximately 50% of individuals with one of the three new AIDS-defining diseases will develop an AIDS-1987 disease or will die within 1 year. Time from AIDS-1993 to AIDS-1987 disease is strongly associated with CD4+ count at diagnosis. AIDS_1993 diagnosis reduced the pre-AIDS-1987 mortality in injecting drug users. Furthermore, approximately 20% of individuals diagnosed with AIDS-1993 disease are expected to die without developing an AIDS-1987 disease. These data should be useful for correcting the AIDS incidence curve in Europe for the effect of the changes in the AIDS definition.

Differences in progression to AIDS between injection drug users and homosexual men with documented dates of seroconversion.

We compared rates of progression to AIDS for 99 injection drug users and 120 homosexual men with documented dates of HIV-1 seroconversion. The crude risk of developing AIDS was higher among homosexual men than injection drug users [relative hazard (RH) = 2.4; 95% confidence interval (CI) = 1.3-4.4]. The relative hazard was slightly smaller among participants with a seroconversion interval of < or = 1 year (RH = 2.2; 95% CI = 1.0-5.2). The effect was partially explained by the inclusion of Kaposi's sarcoma in the AIDS case definition. Excluding those with Kaposi's sarcoma, the relative hazard was 2.0 (95% CI = 1.1-3.8). Using the 1993 AIDS case definition decreased the effect (RH = 1.9; 95% CI = 1.1-3.4). Finally, the high pre-AIDS mortality among injection drug users could partially explain the difference in progression rate between injection drug users and homosexual men. Combining the effect of the above-mentioned factors resulted in a relative hazard of 1.3 (95% CI = 0.7-2.6). Thus, the slower progression to AIDS among injection drug users compared with homosexual men was largely explained by differences in the spectrum of AIDS-defining illnesses, pre-AIDS mortality, and length of seroconversion interval.

Clinical features of early HIV in the Edinburgh City Hospital cohort

In order to describe the clinical features of HIV (non-AIDS), particularly injection drug use (IDU) related HIV, in patients attending the Regional Infectious Diseases Unit in Edinburgh, a prospective review utilizing the WHO staging system of the 680 HIV positive patients, 30% of whom were women and 68% were infected via IDU, was undertaken. Despite the fact that the majority of drug users and heterosexuals enrolled asymptomatic, by 1993, 71% of the patients had developed some HIV related clinical problem. The important clinical problems observed for the cohort were; minor skin problems, minor bacterial infections, major bacterial sepsis, oral thrush, oral hairy leucoplakia, significant weight loss of > 10%, HIV related thrombocytopenia and of course AIDS. Unlike previous reports from other areas, in Edinburgh drug users were not more likely than other risk groups to develop severe bacterial disease. Differences in morbidity and mortality rates by risk group but not by gender were noted but these may well be affected by the very different enrolment pattern observed in the various risk groups. The pre-AIDS mortality rates for drug users were remarkably similar to published rates from other centres.

High mortality among HIV-infected injecting drug users without AIDS diagnosis

To quantify mortality without AIDS diagnosis (pre-AIDS death) among HIV-infected injecting drug users (IDU) and to compare it with that among homosexual men. Municipal Health Service in Amsterdam, The Netherlands. HIV-infected participants of a cohort of homosexual men (recruited since 1984) and a cohort of IDU (recruited since 1985) were followed up to investigate the occurrence of AIDS and pre-AIDS death up to 1 October 1992. Both seroprevalent and seroconverted participants were included. Product-limit estimates of cumulative AIDS incidence and cumulative pre-AIDS mortality were calculated for a competing risks model. Of 455 HIV-infected homosexual men, 127 developed AIDS and two died without a diagnosis of AIDS during follow-up; 31 out of 279 HIV-infected IDU were diagnosed with AIDS and 33 died without an AIDS diagnosis. After 6.5 years of follow-up an estimated 43.7% of the homosexual men had been diagnosed with AIDS and 0.7% had died without an AIDS diagnosis, while 32.7% of the IDU had been diagnosed with AIDS and 19.8% had died without an AIDS diagnosis. After 6.5 years of follow-up one-fifth of a group of HIV-infected IDU had died without being diagnosed with AIDS. This phenomenon seriously limits the number of HIV-infected IDU that may ever be diagnosed with AIDS and should be considered by HIV infection epidemic modellers. The new case definitions for AIDS will limit the number of recorded cases of pre-AIDS death.