HIV-1 infection in rural Africa: is there a difference in median time to AIDS and survival compared with that in industrialized countries?
Morgan, Dilys; Mahe, Cedric; Mayanja, Billy; Okongo, J. Martin; Lubega, Rosemary; Whitworth, James A. G.
From the Medical Research Council Programme on AIDS, Uganda Virus Research Institute, Entebbe, Uganda.
Requests for reprints to: Dr D. Morgan, PHLS Communicable Disease Surveillance Centre, 61 Colindale Ave, London NW9 5EQ, UK.
Received: 13 August 2001;
revised: 27 September 2001; accepted: 3 October 2001.
Sponsorship: this work was funded by the Medical Research Council (UK) and the Department for International Development.
Objectives: To describe the progression times of HIV-1 infection from seroconversion to AIDS and to death, and time from first developing AIDS to death in rural Uganda. Also, to describe the proportion of individuals within the cohort dying with AIDS and the CD4 lymphocyte count before death.
Design: A prospective, longitudinal, population-based cohort.
Methods: Since 1990, 107 HIV-prevalent cases, 168 incident cases and 235 HIV-seronegative controls have been recruited into a cohort in rural Uganda. Participants are recruited from the general population and they are reviewed routinely every 3 months and at other times when ill.
Results: The median time from seroconversion to death was 9.8 years. Age over 40 years at seroconversion was associated with more rapid progression (P < 0.001, log rank test). For the first 4 years of the study, HIV contributed little to the death rates in the HIV incident cases, but after 5 years, the contribution of HIV became greater and was particularly marked in the oldest age group. Survival rates in the cohort were similar to those in the general population. The median time from seroconversion to AIDS was 9.4 years and from AIDS to death was 9.2 months. Of those infected with HIV-1, 80% died with AIDS and 20% had a CD4 count < 10 × 106 cells/l.
Conclusions: Survival with HIV-1 infection is similar in Africa to industrialized countries before the use of antiretroviral therapy; when they do die, many of those in Africa are severely immunosuppressed and most have clinical features of AIDS.
More than 70% of the 30 million adults infected with HIV-1 in the world live in subSaharan Africa and prevalence rates of over 25% have been reported from several African countries , yet little is known about the progression of HIV disease on that continent. Although some studies have suggested that HIV-1 infection progresses more rapidly in Africans [2–4], others have found a similar disease progression to that in industrialized countries [5–8]. However, cohorts of individuals with documented negative and positive HIV tests and hence an estimated date of seroconversion are rare. We are aware of only one study in Africa that has reported the median time from seroconversion to AIDS; this was in a cohort of sex workers in Kenya . Otherwise all reports of survival and AIDS-free time from Africa are based on prevalent cohorts with unknown dates of seroconversion [4,7,10,11].
Uganda was the first government in Africa to acknowledge publicly that an HIV-1epidemic was occurring in the general population. The political leaders took an active stance, and extensive HIV/AIDS prevention programmes were developed through governmental and non-governmental organizations. The high level of HIV/AIDS awareness, which is so obvious in the country today, has probably contributed to the decline in prevalence that has been reported from all over the country, both in sentinel sites and population-based studies [12,13]. The fall has been most pronounced in the younger age groups, a sector that gives a better measure of incidence. In our study area, the prevalence of HIV-1 infection in adults fell significantly from 8.2% in 1989–1990 to 6.9% in 1996–1997, with a non-significant reduction in incident rates from 7.7 to 4.6/1000 person-years of observation over the same period . Despite these encouraging findings, the reality of coping for those who are infected with HIV and of providing treatment remains grim. Although Uganda recently became part of the UNAIDS drug access initiative to reduce the cost of antiretroviral therapy, the per capita GDP (gross domestic product) was around US$100 in 1999–2000 , and so even the subsidized treatment cost is beyond the means of most people. This is particularly so in the rural areas where the majority of Ugandans reside, and where the main occupation is subsistence farming.
Knowledge of progression times and the main clinical problems associated with HIV infection is, therefore, important when trying to plan provision of health services to African populations. This information is also necessary for modelling estimates of the evolution of the epidemic, including the expected number of people living with HIV.
We report rates of progression to AIDS and death in adults with estimated dates of HIV-1 seroconversion enrolled in a clinical cohort in rural Uganda. We also examine the proportion of all participants with HIV infection who died with AIDS, the median survival from first being seen with AIDS and CD4 cell counts before death.
Selection of participants
Participants were recruited from a large general population study based in rural Uganda. The population study was established in 1989 to investigate the dynamics of HIV-1 infection in a population of around 4500 adults residing in 15 neighbouring villages . This is done by annual HIV serosurveys. In 1990, a random selection of individuals found to be HIV positive at the first round of the population study were enrolled into a clinical cohort as prevalent cases of infection. All seroconverters detected during subsequent annual surveys of the population study were invited to enrol as incident cases, along with randomly selected, age-stratified, HIV-negative controls for the HIV-infected subjects. The estimated date of seroconversion of the incident cases was taken as the mid-point between the dates of the last HIV-negative and the first HIV-positive test.
Home visitors contacted and explained the nature of the study to selected individuals and then, if they consented to attend the study clinic, the study was again explained by one of two clinicians. At the enrolment visit, all participants gave informed, written (signed or thumbprint) consent. Clinicians reviewed participants every 3 months and completed a detailed questionnaire about their medical and sexual history. At these routine visits, the participants also had a physical examination. After 1995, CD4 lymphocyte counts were routinely performed in the main laboratory 3 h drive away from the study area using FACSCOUNT (Becton Dickinson, San Jose, California, USA). Any complaints or medical findings were investigated and treated. Participants could also attend for free investigation and treatment of illnesses occurring between routine appointments. For each routine visit, HIV-seropositive participants were categorized according to the clinical and performance scale of the proposed WHO staging system  using a computer algorithm. AIDS is used synonymously with WHO stage 4. The study provided transport and cost of all hospital referrals for the participants and their families.
For reasons of confidentiality, the HIV status of participants in the cohort was unknown to any of the staff at the clinic. This also reduced reporting biases. All participants were strongly encouraged to attend HIV counselling and testing facilities provided by the project in the study villages.
Kaplan–Meier survival methods were used to estimate the median [and interquartile ranges (IQR)], cumulative and survival probabilities [and 95% confidence intervals (CI)] for times to the various endpoints. Log rank test was used to compare survival in different subgroups. All analyses were performed using STATA 6.0. statistical package (Stata Corporation, College Station, Texas, USA).
Analyses of time from seroconversion to AIDS included all incident cases. The endpoint was the date first seen with an AIDS-defining condition, whether at routine or interim visit, and follow-up of an individual was censored at his or her last routine appointment before 31 December 2000.
For time from seroconversion to death, the vital status of all but one of the incident cases of HIV infection was known at the end of 2000, and he was known to be alive at the end of 1997. His follow-up was, therefore, censored at this date. All the living incident cases were censored at the end of 2000. The age-standardized mortality ratio was computed by linking data from the clinical cohort to the large population cohort from which participants are recruited. In order to take into account the increasing age of the population over the study period, a lexis transformation was performed (whereby each individual contributes to the different age groups as their age increases during follow-up).
A comparison of the incidence of death from seroconversion in different age groups is difficult to interpret because it combines HIV attributable deaths and deaths from other causes. Older age groups would be expected to have a greater proportion of deaths from natural causes; therefore, an HIV-attributable death cumulative incidence was computed by age group. For each year from enrolment, the death rate in the HIV-seronegative controls was subtracted from the death rate in the incident cases. A Nelson–Aalen-like cumulative incidence estimator was then obtained by adding these yearly HIV-attributable death rates.
All HIV-infected participants were used in the analysis of survival from developing AIDS. Participants with AIDS on enrolment were excluded. Time was estimated from first being seen with an AIDS-defining condition to death or last visit. Although most participants had only one AIDS-defining condition, if a participant presented with more than one at the same visit, he or she was included in the analyses for all presenting conditions.
Participants were classified as having died with AIDS if they were in WHO stage 4 at their last routine visit or, if they were not, from their medical records held at the clinic or information about the nature of their final illness from family and friends.
To compare survival of people in the cohort, who have regular follow-up and open-access to medical facilities, with those in the general population, who do not, all prevalent cases in the general population study who were infected with HIV-1 during the initial round of analysis in 1989–1990 were considered (cohort joiners and non-cohort). At the end of September 2000, the survival of prevalent cases who were randomly selected and joined the cohort between 1 October and 31 December 1990 was compared with the other prevalent cases not selected for enrolment (but still alive on 1 October 1990). People who were selected but did not enrol were excluded. As for participants in the cohort, home visitors contacted the family and friends of individuals who had moved out the study area to find out if they were still alive and, if they were not, when they died.
By the end of 2000, 107 prevalent and 168 incident cases of HIV-1 infection and 235 HIV-seronegative controls had been enrolled into the cohort. Details of these participants are given in Table 1. The male incident cases were significantly older than the females (P < 0.001, Mann–Whitney), which reflects the transmission pattern of HIV in this rural community. At enrolment, 82 (77%) prevalent and 143 (85%) incident subjects were asymptomatic. Compliance rates have remained high throughout the study. During 2000, there were 1137 visits made out of 1230 scheduled visits for available participants, making the compliance rate 92.4%.
The 168 incident cases had a median of 12.3 months (IQR, 11.0–24.2) between the last negative and first positive HIV-1 test. The median period between the estimated date of seroconversion and enrolment into the cohort was 12.9 months (IQR, 8.0–22.0). The median follow-up from seroconversion was 5.6 years (IQR, 3.6–7.3).
Of the incident cases, 44 developed AIDS. The median time from seroconversion to AIDS was 9.4 years (IQR, 5.5–10.1). The cumulative probability of AIDS was 22% (95% CI, 16–31), 36% (95% CI, 27–46) and 45% (95% CI, 34–57) at 5, 7 and 9 years, respectively, following seroconversion. Older age group (≥ 40 years) at seroconversion was associated with a faster progression to AIDS (P < 0.001, log rank test).
Among the incident cases, 47 died during 920.7 person-years of follow - up (age-standardized mortality rate 67.0/1000 person-years). The median survival from seroconversion was 9.8 years (IQR, 6.1 to > 10.3). The cumulative probability of death from seroconversion is shown in Fig. 1.
There were 10, 18 and 19 deaths among of 65, 68 and 35 participants in age groups 15–24, 25–39 and ≥ 40 years, respectively, at seroconversion. The cumulative probability of survival in each age group at 7 years was 79% (95% CI, 63–88), 72% (95% CI, 56–83) and 20% (95% CI, 6–40), respectively (Fig. 2). There was a lower probability of survival in the older age group compared with the younger age groups (P < 0.0001, log rank). Nineteen HIV-seronegative controls died during 1720.6 person-years of follow-up and the cumulative survival at 7 years was 92% (95% CI, 87–95). The age-standardized mortality rate was 8.5/1000 person-years. A significantly higher death rate was also seen in the HIV-seronegative controls aged ≥ 40 years on enrolment (P < 0.0001, log rank test). The HIV-attributable cumulative incidence of death is shown in Fig. 3. This shows that HIV-1 contributes little to the death rates in the HIV incident cases for the first few years in the cohort but then its contribution becomes greater; this is particularly marked in the oldest age group.
All together, 90 HIV-seropositive participants developed AIDS during follow-up. The median survival from developing AIDS to death was 9.2 months (IQR, 2.2–23.6). A CD4 lymphocyte count at, or within 3 months, of developing AIDS was available for 70 participants; the median count was 126 × 106 cells/l (IQR, 40–318). Survival was 3 to 4 months for those whose AIDS-defining conditions were wasting syndrome, candidiasis of the oesophagus and Kaposi's sarcoma. However, survival was over 20 months for participants with chronic herpes simplex virus infections and extrapulmonary tuberculosis as their AIDS-defining conditions. We have shown previously that survival depended on the initial AIDS-defining illness and there was little relationship between median survival and the CD4 cell count of the AIDS-defining conditions .
Of the 121 HIV-seropositive participants who died, 74 (61%) had AIDS at their last routine clinic visit. A further 11 had a history from relatives of an AIDS-like illness before death; for 15 a cause of death could not be ascertained. Consequently, 80% (85/106) of HIV-infected participants were in WHO stage 4 at their last visit or were reported to have died with AIDS.
The last recorded CD4 cell counts within 6 months before death were available for 68 HIV-seropositive and 12 HIV-seronegative participants. The median CD4 cell count before death was 61 × 106 cells/l (IQR, 17–199) for the HIV-seropositive individuals and 716 × 106 cells/l (IQR, 581–1103) in the HIV-seronegative controls. The CD4 cell count was < 10 × 106 cells/l prior to death in 22% of the HIV-infected participants.
A comparison of the survival of the 71 prevalent cases who joined the cohort between 1 October and 31 December 1990 and the 126 subjects who were not invited is shown in Fig. 4. There was no difference in survival times (P = 0.63, log rank test). Although there was a greater proportion of males in the cohort group (P = 0.009, chi-squared test) because of preferential selection aiming to recruit similar numbers of males and females, there was no difference in age group distribution (P = 0.44, chi-squared test). Many had moved away from the study area either permanently or for varying periods of time. Two individuals, one who joined the cohort and one who did not, were lost to follow-up. Another, not invited to join the cohort, was known to have died, but the date of death was not known. These three individuals were, therefore, excluded from the analysis.
This is the first report of median survival with HIV-1 infection in an incident population-based cohort in Africa. The median survival from seroconversion was 9.8 years, which shows that HIV infection is not a more rapidly progressive disease in Africans. Once AIDS developed, the median survival was only 9.2 months, which is similar to that reported early in the epidemic in industrialized countries although much shorter than survival in these countries now. The majority of HIV-infected persons die with AIDS and they often have very low CD4 cell counts at the time of death.
This cohort has a number of strengths. It provides 10 years of longitudinal data on a rural population-based cohort. There are 168 incident cases with dates of seroconversion that have been followed for a median of over 5.5 years. There is an HIV-seronegative control group to measure background rates of morbidity and mortality in the population. Participants are seen routinely every 3 months and compliance is good, with over 90% of those available in the study area being seen at routine visits. There are data on 9334 routine visits, 4195 in HIV-seropositive participants. Follow-up is comprehensive; intensive, detailed clinical case notes are kept at the clinic and information about interim visits is recorded on the questionnaire. CD4 lymphocyte counts and microbiological diagnoses were also available for the last 5 years of the study. A network of home visitors followed people not seen at routine appointment. By the end of 2000, the vital status was known for all but two of the HIV-infected participants.
Comparing progression times in the cohort with those reported from industrialized countries is problematic since progression to AIDS and death depends on frequency of follow-up and mode of transmission, available treatment and chemoprophylaxis in the cohort being studied. Most cohort studies reporting from industrialized countries are from one exposure group or, if composed of several exposure groups, have few individuals with HIV-1 acquired by heterosexual transmission and, therefore, median survival for this group is not readily available. Some studies have reported a difference in survival between different transmission categories [19,20], but age at seroconversion is thought to be a major factor explaining these differences . Comparing times to AIDS is further complicated by changes and different definitions of AIDS employed by each study. The median time to AIDS was 9.4 years in our Ugandan cohort. This is comparable with cohorts in industrialized countries before the better management of HIV infection, when the median survival to AIDS was around 9 or 10 years but ranged from 5.7 to over 12 years [19–25]. We found that the median survival from seroconversion to death was 9.8 years, which is considerably longer than has been expected in African populations. This is also comparable to survival times of around 10 years (ranging from 8.3 to approximately 13 years) reported by cohort studies in industrialized countries prior to the widespread use of antiretroviral therapy [19,23–24,26]. Several studies have shown that age at seroconversion is a major factor in determining survival, with wide survival differences between younger and older age groups [22,26]. If survival by age group at seroconversion is considered in our cohort, there is no statistical difference in survival between the younger age groups, but those aged ≥ 40 years at seroconversion had a much lower survival. Older people are more likely to die irrespective of HIV disease; to remove this confounding factor, the HIV-attributable cumulative incidence was determined. This was minimal for the first 4 years in the study but increased thereafter, with the greatest effect in those aged ≥ 40 years at seroconversion.
The survival rates in the cohort were achieved by regular clinical review and prompt treatment of conditions diagnosed using basic laboratory facilities and standard drugs from the WHO essential drug list, which should be available in any health post throughout Africa. Participants also received intensive treatment even if it was suspected that they were in late-stage disease. Treatment was free because, in this very poor area, even a minimal charge for treatment would deter patients seeking care for frequent HIV-related events. It was, therefore, disappointing to find that survival was similar in the participants who formed the randomly selected prevalent HIV-seropositive cases of the cohort in 1989–1990 to that in prevalent cases who were not invited to join the cohort. Home visitors contacted friends and relatives of those who had enrolled in the cohort and had not been seen in the clinic, and so if they had died we would have heard about it shortly after the death. For those who did not enrol and were not living in the study area, home visitors made enquiries of family and friends during October 2000, so many of those who had died had done so several years before. Therefore, there may have been recall bias but this is unlikely for something as important as approximate date of death. Consequently, although considerable thought has been given to identifying possible biases, we do not have a good explanation of this lack of difference. However, it is a common and major assumption that medical care is very effective in reducing morbidity and mortality, whereas, on a population basis, social and economic interventions are more likely to produce changes in mortality . It does mean, though, that our findings are likely to be representative of survival in the general population.
The median survival from developing AIDS in the cohort was 9.2 months. Although short, this is similar to the average of 10 months reported in industrialized countries early in the HIV epidemic [28–30]. However, the course of AIDS in developed countries has changed with better management of HIV infection through the use of prophylaxis and antiretroviral drugs. Survival after an AIDS diagnosis in the United Kingdom increased from 10.6 months before 1987 to over 19 months in 1991 . The survival of Africans attending a clinic in London was 22 months from attending with an AIDS-defining condition . With highly active antiretroviral therapy, the incidence of AIDS has been reduced further and the survival with AIDS has been prolonged .Of participants for whom a cause of death could be ascribed, 80% died with AIDS. This is in contrast to three other studies in Africa, where only 11% ,46%  and 66%  of deaths in HIV-positive subjects were reported to have been caused by AIDS, based on the WHO (Bangui) clinical case definition. In our study, we used the WHO staging system (which needs a positive HIV-1 test) . This, plus the coverage and frequency of follow-up, probably accounts for the higher proportion of deaths from AIDS in our study. As we have seen, survival following AIDS is usually short in Africa; therefore the frequency and quality of follow-up will determine the proportion of deaths with AIDS that are identified
The median CD4 cell count within 6 months of death was 61 × 106 cells/l. However, a quarter of those who died had a count of < 17 × 106 cells/l and some of these people survived many months with CD4 cell counts of this level. In a study of hospital admissions in Abidjan, the majority of persons with HIV had profound immunosuppression, as indicated by admission with a median CD4 cell count of 84 × 106 cells/l . Therefore, again contrary to first thought, people in Africa do survive, and often for quite long periods, with very low CD4 cell counts.
In conclusion, our study shows that African adults infected with HIV-1 survive on average around 10 years after seroconversion; when they do die, many are severely immunosuppressed and most have clinical features of AIDS.
We wish to thank all the clinic staff and, most importantly, the participants themselves.
1. UNAIDS. Report on the Global HIV/AIDS Epidemic, June 2000.
Geneva: UNAIDS; 2000.
2. Colebunders R, Ryder R, Francis H. et al
. Seroconversion rate, mortality and clinical manifestations associated with the receipt of a human immunodeficiency virus-infected blood transfusion in Kinshasa, Zaire
. J Infect Dis 1991, 164: 450–456.
3. N'Galy B, Ryder RW, Kapita B. et al
. Human immunodeficiency virus infection among employees in an African hospital. N Engl J Med 1988, 319: 1123–1127.
4. Whittle H, Egboga A, Todd J. et al
. Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-2 infection. AIDS 1992, 6: 685–689.
5. Mann JM, Bilak K, Colebunders RL. et al
. Natural history of human immunodeficiency virus infection in Zaire
. Lancet 1986, ii: 707–709.
6. Marlink R, Kanki P, Thior I. et al
. Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 1994, 265: 1587–1590.
7. Leroy V, Msellati P, Lepage P. et al
. Four years of natural history of HIV-1 infection in African women: a prospective cohort study in Kigali (Rwanda), 1988–1993. J Acquir Immune Defic Syndr Hum Retrovirol 1995, 9: 415–421.
8. French N, Mujugira A, Nakiyingi J, Mulder D, Janoff EN, Gilks CF. Immunological and clinical stages in HIV-1 infected adults are comparable and provide no evidence of rapid progression but poor survival with advanced disease. J Acquir Immune Def Syndr Hum Retrovirol 1999, 22: 509–516.
9. Anzala OA, Nakelkerke NJD, Bwayo JJ. et al
. Rapid progression to disease in African sex workers with human immunodeficiency virus type 1 infection. J Infect Dis 1995, 171: 686–689.
10. Lindan CP, Allen S, Serufilira A. et al
. Predictors of mortality among HIV-infected women in Kigali, Rwanda. Ann Intern Med 1992, 116: 320–328.
11. Morgan D, Maude GH, Malamba SS. et al
. HIV-1 disease progression and AIDS defining disorders in rural Uganda. Lancet 1997, 305: 245–250.
12. Kilian AHD, Gregson S, Ndyanabangi B. et al
. Reductions in risk behaviour provide the most consistent explanation for declining HIV-1 prevalence in Uganda. AIDS 1999, 13: 391–398.
13. Asiimwe-Okiror G, Opio AA, Musinguzi J. et al
. Change in sexual behaviour and decline in HIV infection among young pregnant women in urban Uganda. AIDS 1997, 11: 1757–1763.
14. Kamali A, Carpenter LM, Whitworth JAG. et al
. Seven-year trends in HIV-1 infection rates, and changes in sexual behaviour, among adults in rural Uganda. AIDS 2000, 114: 427–434.
15. Uganda Bureau of Statistics. 2000 Statistical Abstract.
Kampala: Industrial Graphic Systems for UBOS; June 2000.
16. Mulder DW, Nunn AJ, Wagner U-H, Kamali A, Kengeya-Kayondo JF. HIV-1 incidence and HIV-1-associated mortality in a rural Ugandan population cohort. AIDS 1994, 8: 87–92.
17. World Health Organization. Acquired immune deficiency syndrome (AIDS): interim proposal for a WHO staging system for HIV-1 infection and disease
. Wkly Epidemiol Rec 1990, 65: 221–228.
18. Morgan D, Malamba SS, Orem J, Mayanja B, Okongo M, Whitworth JAG. Survival by AIDS-defining condition in rural Uganda. Sex Trans Infect 2000, 76: 193–197.
19. Multicohort Analysis Project Workshop. Immunological markers of AIDS progression: consistency across five HIV-infected cohorts, part 1. AIDS 1994, 8: 911–921.
20. Pehrson P, Lindbäck S, Lidman C, Gaines H, Gieseke J. Longer survival after HIV infection for injecting drug users than for homosexual men: implications for immunology. AIDS 1997, 11: 1007–1012.
21. Pezzotti P, Galai N, Vlahov D for the ALIVE and ISS groups. Direct comparison of time to AIDS and infectious disease death between HIV seroconverter injection drug users in Italy and the United States: results from the ALIVE and ISS studies. J Acquir Immune Defic Syndr Hum Retrovirol 1999, 20: 275–282.
22. Collaborative Group on AIDS Incubation and HIV Survival including the CASCADE EU Concerted Action. Time from HIV-1 seroconversion to AIDS and death before widespread use of highly active retroviral therapy: a collaborative re-analysis
. Lancet 2000, 355: 1131–1137.
23. Veugelers PJ, Page KA, Tindall B. et al
. Determinants of HIV disease progression among homosexual men registered in the tricontinental seroconvertor study. Am Journ Epidemiol 1994, 140: 747–758.
24. UK Register of HIV Seroconvertors Steering Committee. The AIDS incubation period in the UK estimated from a national register of HIV seroconvertors. AIDS 1998, 12: 659–667.
25. van Benthem BHB, Veugelers PJ, Cornelisse PGA. et al
. Is AIDS a floating pont between HIV seroconversion and death? Insights from the tricontinental seroconvertor study. AIDS 1998, 12: 1039–1045.
26. Koblin BA, van Benthem BHB, Buchbinder SP. et al
. Long-term survival after infection with human immunodeficiency virus type1 (HIV-1) among homosexual men in hepatitis B vaccine trial cohorts in Amsterdam, New York City, and San Francisco, 1978–1995. Am J Epidemiol 1999, 150: 1026–1030.
27. Navarro V. Assessment of the World Health Report 2000. Lancet 2000, 356: 1598–1601.
28. Friedland GH, Saltzman B, Vileno J. et al
. Survival differences in patients with AIDS. J Acquir Immune Syndr Hum Retrovirol 1991, 4: 144–153.
29. Lemp GF, Payne SF, Neal D. et al
. Survival trends for patients with AIDS
. JAMA 1990, 263: 402–406.
30. Moore RD, Hidalgo J, Sugland BW. et al
. Zidovudine and the natural history of the acquired immunodeficiency syndrome. N Engl J Med 1991, 324: 1412–1116.
31. Rogers PA, Whitmore-Overton SE, Evans BG. et al
. Survival of adults with AIDS in the United Kingdom. Commun Dis Rep Rev 1997, 7: R93–R100.
32. Del Amo J, Petruckevitch A, Phillips A. et al
. Disease progression and survival in HIV-1-infected Africans in London. AIDS 1998, 12: 1203–1209.
33. Fleming PL, Ward JW, Karon JM. et al
. Declines in AIDS incidence and deaths in the USA: a signal change in the epidemic. AIDS 1998, 12 (suppl A): S55–S61.
34. Todd J, Balira R, Grosskurth H. et al
. HIV-associated adult mortality in a rural Tanzanian population. AIDS 1997, 11: 801–807.
35. Grant AD, Djomand GD, Smets P. et al
. Profound immunosuppression across the spectrum of opportunistic disease among hospitalized HIV-infected adults in Abidjan, Côte d'Ivoire. AIDS 1997, 11: 1357–1364.
This article has been cited 155 time(s).
Applied Mathematical ModellingGlobal stability for an HIV/AIDS epidemic model with different latent stages and treatmentApplied Mathematical Modelling
2012 American Control Conference (Acc)
Controlling AIDS progression in patients with rapid HIV dynamics
2012 American Control Conference (Acc), ():
Proceedings of the National Academy of Sciences of the United States of AmericaProspects of elimination of HIV with test-and-treat strategyProceedings of the National Academy of Sciences of the United States of America
Journal of General VirologyHuman immunodeficiency virus type 1 gp120 envelope characteristics associated with disease progression differ in family members infected with genetically similar virusesJournal of General Virology
26Th Ieee International Conference on Micro Electro Mechanical Systems (Mems 2013)
An Intergated Microfluidic System for Detecting Human Immunodeficiency Virus in Blood Samples
26Th Ieee International Conference on Micro Electro Mechanical Systems (Mems 2013), ():
Plos OneCost-Effectiveness of Pre-Exposure Prophylaxis (PrEP) in Preventing HIV-1 Infections in Rural Zambia: A Modeling StudyPlos One
World DevelopmentDoes Prime-Age Mortality Reduce Per-Capita Household Income? Evidence from Rural ZambiaWorld Development
AIDSImpact of the HIV epidemic on population and household structure: the dynamics and evidence to dateAIDS
Bulletin of the World Health Organization
Monitoring the scale-up of antiretroviral therapy programmes: methods to estimate coverage
Bulletin of the World Health Organization, 84(2):
Bmc Public HealthImpact of DOTS expansion on tuberculosis related outcomes and costs in HaitiBmc Public Health
Journal of Infectious DiseasesCD4 cell count distributions and HIV-associated mortality in AfricaJournal of Infectious Diseases
International Journal of Std & AIDS
Association between active GB virus-C (hepatitis G) infection and HIV-1 disease in Uganda
International Journal of Std & AIDS, 18(4):
Indian Journal of Medical Research
Chemokine profile among human immunodeficiency virus-1 (HIV-1) infected individuals from southern India
Indian Journal of Medical Research, 127(2):
Epidemiology and InfectionHIV epidemic trend and antiretroviral treatment need in Karonga District, MalawiEpidemiology and Infection
HIV-1 disease progression and mortality before the introduction of highly active antiretroviral therapy in rural Uganda
Survival of blood donors and their spouses with HIV-1 subtype E (CRF01 A_E) infection in northern Thailand, 1992-2007
Clinical and Experimental ImmunologyFactors associated with CD4 lymphocyte counts in HIV-negative Senegalese individualsClinical and Experimental Immunology
AIDSStochastic simulation of the impact of antiretroviral therapy and HIV vaccines on HIV transmission; Rakai, UgandaAIDS
Journal of Biological ChemistryThe glutamine-rich region of the HIV-1 Tat protein is involved in T-cell apoptosisJournal of Biological Chemistry
Proceedings of the Royal Society B-Biological SciencesRole of avidity and breadth of the CD4 T cell response in progression to AIDSProceedings of the Royal Society B-Biological Sciences
Current HIV Research
Lability of antiretroviral drug resistance mutations - Correlates with immunological and virological responses
Current HIV Research, 5(4):
Transactions of the Royal Society of Tropical Medicine and HygienePatient retention and attrition on antiretroviral treatment at district level in rural MalawiTransactions of the Royal Society of Tropical Medicine and Hygiene
Migrants from Sub-Saharan Africa in the Swiss HIV Cohort Study: access to antiretroviral therapy, disease progression and survival
Scandinavian Journal of Infectious DiseasesThe natural course of disease following HIV-1 infection in Dar es Salaam, Tanzania: A study among hotel workers relating clinical events to CD4(+) T-lymphocyte countsScandinavian Journal of Infectious Diseases
Plos MedicineThe potential impact of male circumcision on HIV in sub-Saharan AfricaPlos Medicine
Bulletin of the World Health Organization
Progression to WHO criteria for antiretroviral therapy in a 7-year cohort of adult HIV-1 seroconverters in Abidjan, Cote d'Ivoire
Bulletin of the World Health Organization, 85(2):
Does the, private sector care about AIDS? Evidence from firm surveys in East Africa
Indian Journal of Medical Research
Investigation of apoptotic markers among human immunodeficiency virus (HIV-1) infected individuals
Indian Journal of Medical Research, 128(6):
HIV incidence and poverty in Manicaland, Zimbabwe: is HIV becoming a disease of the poor?
Sexual HealthRapidly ageing HIV epidemic among men who have sex with men in AustraliaSexual Health
Proceedings of the National Academy of Sciences of the United States of AmericaCritique of early models of the demographic impact of HIV/AIDS in sub-Saharan Africa based on contemporary empirical data from ZimbabweProceedings of the National Academy of Sciences of the United States of America
Survival after HIV infection in the pre-antiretroviral therapy era in a rural Tanzanian cohort
HIV-infected Rwandan women have a high frequency of long-term survival
Mortality levels and trends by HIV serostatus in rural South Africa
VirologyReplication of HIV-1 deleted Nef mutants in chronically immune activated human T cellsVirology
The changing clinical epidemiology of AIDS in the highly active antiretroviral therapy era
Plos MedicinePatient retention in antiretroviral therapy programs in sub-Saharan Africa: A systematic reviewPlos Medicine
VaccineTat mutations in an African cohort that do not prevent transactivation but change its immunogenic propertiesVaccine
Journal of Infectious Diseases
Schistosomiasis and HIV-1 infection in rural Zimbabwe: Effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load
Journal of Infectious Diseases, 192():
Effect of HIV on work-related injury rates in South African gold miners
Journal of Infectious Diseases
HIV infection, Antiretroviral therapy, and CD4(+) cell count distributions in African populations
Journal of Infectious Diseases, 194():
Annals of EpidemiologyMale and female circumcision associated with prevalent HIV infection in virgins and adolescents in Kenya, Lesotho, and TanzaniaAnnals of Epidemiology
Challenges in delivering antiretroviral treatment in resource poor countries
National Medical Journal of India
The natural history of human immunodeficiency virus infection among adults in Mumbai
National Medical Journal of India, 16(3):
AIDSThe population impact of HIV on fertility in sub-Saharan AfricaAIDS
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIVEffectiveness and cost effectiveness of early and late prevention of HIV/AIDS progression with antiretrovirals or antibiotics in Southern African adultsAIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV
Clinical Infectious Diseases
Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women
Clinical Infectious Diseases, 42(9):
Sexually Transmitted InfectionsModelling the cost effectiveness of rapid point of care diagnostic tests for the control of HIV and other sexually transmitted infections among female sex workersSexually Transmitted Infections
Tropical Medicine & International HealthChanging association between schooling levels and HIV-1 infection over 11 years in a rural population cohort in south-west UgandaTropical Medicine & International Health
Survival of HIV-infected treatment-naive individuals with documented dates of seroconversion in Rakai, Uganda
The natural history of HIV-1 subtype E infection in young men in Thailand with up to 14 years of follow-up
Journal of Medical Internet ResearchInformation systems for patient follow-up and chronic management of HIV and tuberculosis: A life-saving technology in resource-poor areasJournal of Medical Internet Research
Plos OneGenital Herpes Has Played a More Important Role than Any Other Sexually Transmitted Infection in Driving HIV Prevalence in AfricaPlos One
Chemical Engineering ScienceLong-term HIV dynamics subject to continuous therapy and structured treatment interruptionsChemical Engineering Science
International Journal of Std & AIDSDouble standards in research ethics, health-care safety, and scientific rigour allowed Africa's HIV/AIDS epidemic disastersInternational Journal of Std & AIDS
Future VirologyViral tropism, fitness and pathogenicity of HIV-1 subtype CFuture Virology
Sexually Transmitted InfectionsUsing mathematical modelling to estimate the impact of periodic presumptive treatment on the transmission of sexually transmitted infections and HIV among female sex workersSexually Transmitted Infections
International Journal of Epidemiology
Human immunodeficiency virus type 1 Western blot: revised diagnostic criteria with fewer indeterminate results for epidemiological studies in Africa
International Journal of Epidemiology, 31(5):
Scandinavian Journal of Infectious DiseasesClinical progression in early and late stages of disease in a cohort of individuals infected with human immunodeficiency virus-2 in Guinea-BissauScandinavian Journal of Infectious Diseases
Journal of Infectious Diseases
Low CD4 T cell counts before HIV-1 seroconversion do not affect disease progression in Ethiopian factory workers
Journal of Infectious Diseases, 192(5):
Tropical Medicine & International Health
The effect of malaria on mortality in a cohort of HIV-infected Ugandan adults
Tropical Medicine & International Health, 10(9):
LancetShort-term risk of AIDS or death in people infected with HIV-1 before antiretroviral therapy in South Africa: a longitudinal studyLancet
Delayed presentation for human immunodeficiency virus (HIV) care among veterans - A problem of access or screening?
Medical Care, 45():
Plos MedicineEstimating incidence from prevalence in generalised HIV epidemics: Methods and validationPlos Medicine
AIDS Research and Human RetrovirusesModified Kigali combined staging predicts risk of mortality in HIV-Infected adults in Lusaka, ZambiaAIDS Research and Human Retroviruses
International Journal of Std & AIDSNon-vertical HIV transmission to children in sub-Saharan AfricaInternational Journal of Std & AIDS
ScienceHIV decline associated with behavior change in Eastern ZimbabweScience
Proceedings of the National Academy of Sciences of the United States of AmericaVariation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesisProceedings of the National Academy of Sciences of the United States of America
Sexually Transmitted InfectionsInterpreting declines in HIV prevalence: impact of spatial aggregation and migration on expected declines in prevalenceSexually Transmitted Infections
Epidemiology of non-Hodgkin lymphomas and other haemolymphopoietic neoplasms in people with AIDS
Lancet Oncology, 4(2):
Tropical Medicine & International Health
The impact of HIV/AIDS on labour productivity in Kenya
Tropical Medicine & International Health, 9(3):
Activation by malaria antigens renders mononuclear cells susceptible to HIV infection and re-activates replication of endogenous HIV in cells from HIV-infected adults
Parasite Immunology, 26(5):
Lancet Infectious Diseases
Towards universal access to HIV prevention, treatment, care, and support: the role of tuberculosis/HIV collaboration
Lancet Infectious Diseases, 6(8):
Plos OneWhen Did HIV Incidence Peak in Harare, Zimbabwe? Back-Calculation from Mortality StatisticsPlos One
VaccineUse of predictive markers of HIV disease progression in vaccine trialsVaccine
Population Studies-A Journal of DemographyComparison of household-survey estimates with projections of mortality and orphan numbers in sub-Saharan Africa in the era of HIV/AIDSPopulation Studies-A Journal of Demography
Clinical Infectious Diseases
Efficacy of Antiretroviral therapy in resource-poor settings: Are outcomes comparable to those in the developed world?
Clinical Infectious Diseases, 41():
Journal of Infectious Diseases
Amplified HIV transmission during early-stage infection
Journal of Infectious Diseases, 193(4):
Changing patterns of adult mortality as the HIV epidemic matures in Manicaland, eastern Zimbabwe
Dual HIV-1 infection associated with rapid disease progression
Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment
Antiviral Therapy, 13():
Southeast Asian Journal of Tropical Medicine and Public Health
HIV-1 Subtype B Tat Gene Activities and Disease Progression in HIV-1 Crf01_Ae Infection
Southeast Asian Journal of Tropical Medicine and Public Health, 40(4):
AIDS Patient Care and StdsRace, Outpatient Mental Health Service Use, and Survival After an AIDS Diagnosis in the Highly Active Antiretroviral Therapy EraAIDS Patient Care and Stds
Journal of Infectious Diseases
Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda
Journal of Infectious Diseases, 191(9):
African Development Review-Revue Africaine De DeveloppementARV Treatment and Time Allocation to Household Tasks: Evidence from KenyaAfrican Development Review-Revue Africaine De Developpement
ScienceAntiretroviral drugs for tuberculosis control in the era of HIV/AIDSScience
Journal of General Internal Medicine
Assessing missed opportunities for HIV testing in medical settings
Journal of General Internal Medicine, 19(4):
Journal of Oral Pathology & Medicine
Current trends of HIV disease of the mouth
Journal of Oral Pathology & Medicine, 34(9):
Sexually Transmitted InfectionsMeasuring trends in prevalence and incidence of HIV infection in countries with generalised epidemicsSexually Transmitted Infections
Journal of Development EconomicsHow does the impact of an HIV/AIDS information campaign vary with educational attainment? Evidence from rural UgandaJournal of Development Economics
Journal of Infectious DiseasesScaling up antiretroviral therapy in South Africa: The impact of speed on survivalJournal of Infectious Diseases
Journal of Infectious DiseasesHIV-1 transmission, by stage of infectionJournal of Infectious Diseases
Transactions of the Royal Society of Tropical Medicine and HygieneUnacceptable attrition among WHO stages 1 and 2 patients in a hospital-based setting in rural Malawi: can we retain such patients within the general health system?Transactions of the Royal Society of Tropical Medicine and Hygiene
Hematology-Oncology Clinics of North AmericaEpidemiology of AIDS-related malignancies - An international perspectiveHematology-Oncology Clinics of North America
Nature ImmunologyScience, medicine and research in the developing world: a perspectiveNature Immunology
Epidemiology and InfectionBehaviour change and competitive exclusion can explain the diverging HIV-1 and HIV-2 prevalence trends in Guinea-BissauEpidemiology and Infection
Plos OnePotential Impact of Antiretroviral Chemoprophylaxis on HIV-1 Transmission in Resource-Limited SettingsPlos One
Mathematical BiosciencesOn the intra-host dynamics of HIV-1 infectionsMathematical Biosciences
Sexually Transmitted InfectionsProjecting the demographic impact of AIDS and the number of people in need of treatment: updates to the Spectrum Projection PackageSexually Transmitted Infections
Tropical Medicine & International HealthFinding patients eligible for antiretroviral therapy using TB services as entry point for HIV treatmentTropical Medicine & International Health
Annual Review of SociologyOld inequalities, new disease: HIV/AIDS in sub-Saharan AfricaAnnual Review of Sociology
Journal of Infectious DiseasesEffect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infectionJournal of Infectious Diseases
Applied EconomicsA cost-benefit analysis of female primary education as a means of reducing HIV/AIDS in TanzaniaApplied Economics
World Bank Economic ReviewDoes Education Affect HIV Status? Evidence from five African CountriesWorld Bank Economic Review
A Test of the New Variant Famine Hypothesis: Panel Survey Evidence from Zambia
World Development, 38(3):
Tropical Medicine & International HealthUsing vital registration data to update mortality among patients lost to follow-up from ART programmes: evidence from the Themba Lethu Clinic, South AfricaTropical Medicine & International Health
Tropical Medicine & International HealthPatient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007-2009: systematic reviewTropical Medicine & International Health
Mortality of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients in a clinic-based cohort in The Gambia
International Journal of Std & AIDS
Evidence of shorter incubation period of HIV-1 in Mumbai, India
International Journal of Std & AIDS, 14(7):
AIDSSurvival of HIV-1 and HIV-2 perinatally infected children in The GambiaAIDS
AIDSThe empirical evidence for the impact of HIV on adult mortality in the developing world: data from serological studiesAIDS
Demographic ResearchModelling the demographic impact of HIV/AIDS in South Africa and the likely impact of interventionsDemographic Research
Plos MedicineThe impact of monitoring HIV patients prior to treatment in resource-poor settings: Insights from mathematical modellingPlos Medicine
International Journal of Public HealthComparison of HIV-infected patients' characteristics, healthcare resources use and cost between native and migrant patientsInternational Journal of Public Health
Time from HIV seroconversion to death: a collaborative analysis of eight studies in six low and middle-income countries before highly active antiretroviral therapy
AIDS Education and Prevention
"What worked?": The evidence challenges in determining the causes of HIV prevalence decline
AIDS Education and Prevention, 20(3):
Journal of Human Resources
The economic impact of AIDS treatment - Labor supply in Western Kenya
Journal of Human Resources, 43(3):
Chemical Engineering SciencePlanning of patient-specific drug-specific optimal HIV treatment strategiesChemical Engineering Science
Ethnicity & Disease
Prediction of the Interaction of HIV-1 Integrase and Its Dicaffeoylquinic Acid Inhibitor Through Molecular Modeling Approach
Ethnicity & Disease, 20(1):
Journal of Infectious Diseases
Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda
Journal of Infectious Diseases, 185(9):
HIV and population dynamics: A general model and maximum-likelihood standards for East Africa
Bulletin of the World Health Organization
The natural history of HIV-1 and HIV-2 infections in adults in Africa: a literature review
Bulletin of the World Health Organization, 82(6):
Pre-seroconversion immune status predicts the rate of CD4 T cell decline following HIV infection
Journal of Infectious Diseases
Does tuberculosis increase HIV load?
Journal of Infectious Diseases, 190(9):
Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design
AIDS and BehaviorUganda's HIV prevention success: The role of sexual behavior change and the national response. Commentary on Green et al. (2006)AIDS and Behavior
Journal of InfectionImplications of HIV diversity for the HIV-1 pandemicJournal of Infection
Future MicrobiologyDoes the success of HIV treatment depend on gender?Future Microbiology
European Physical Journal-Special TopicsTransmission of HIV in sexual networks in sub-Saharan Africa and EuropeEuropean Physical Journal-Special Topics
Journal of Infectious DiseasesFactors Associated With Mortality of HIV-Positive Clients Receiving Methadone Maintenance Treatment in ChinaJournal of Infectious Diseases
Bulletin of Mathematical BiologyMathematical Insights in Evaluating State Dependent Effectiveness of HIV Prevention InterventionsBulletin of Mathematical Biology
Plos OnePopulation-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence SettingsPlos One
Plos OneSex Role Segregation and Mixing among Men Who Have Sex with Men: Implications for Biomedical HIV Prevention InterventionsPlos One
JAIDS Journal of Acquired Immune Deficiency SyndromesEndpoints and Regulatory Issues in HIV Vaccine Clinical Trials: Lessons From a WorkshopJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesPlasma HIV-1 RNA to Guide Patient Selection for Antiretroviral Therapy in Resource-Poor Settings: Efficiency Related to Active Case FindingJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesAdult Mortality and Erosion of Household Viability in AIDS-Afflicted Towns, Estates, and Villages in Eastern ZimbabweJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesPredictors of Mortality in a Cohort of HIV-1-Infected Adults in Rural AfricaJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesHigh Rates of Survival, Immune Reconstitution, and Virologic Suppression on Second-Line Antiretroviral Therapy in South AfricaJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesPotential Impact of Antiretroviral Therapy on HIV-1 Transmission and AIDS Mortality in Resource-Limited SettingsJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesHIV-2 CRF01_AB: First Circulating Recombinant Form of HIV-2JAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesAnalytic Insights Into the Population Level Impact of Imperfect Prophylactic HIV VaccinesJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesCost-Effectiveness of Alternative Strategies for Initiating and Monitoring Highly Active Antiretroviral Therapy in the Developing WorldJAIDS Journal of Acquired Immune Deficiency Syndromes
The Pediatric Infectious Disease JournalEarly Clinical Outcomes in Children Enrolled in Human Immunodeficiency Virus Infection Care and Treatment in LesothoThe Pediatric Infectious Disease Journal
Sexually Transmitted DiseasesHow Important Are Unsafe Medical Injections in the Spread of HIV in Africa?Sexually Transmitted Diseases
HIV-1; rural Africa; survival; AIDS
© 2002 Lippincott Williams & Wilkins, Inc.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Highlight selected keywords in the article text.
Data is temporarily unavailable. Please try again soon.
Readers Of this Article Also Read