Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis

Babiker, Abdel; Darby, Sarah C.; Angelis, Daniela De; Kwart, D; Porter, Kholoud; Beral,; Darbyshire, Janet; Day, NE; Gill, Noël; Ra, Chisei; Prins, Maria; Benthem, Birgit van; Dabis, F; Marimoutou, Catherine; Ruíz, Isabel; Tusell, J; Altisent, Carmen; Evatt, Bruce L.; Jaffe, Harold W.; Kirk, Ole; Pedersen, Court; Rosenberg, Philip S.; Goedert, JamesJ.; Biggar, R J; Melbye, Mads; Brettie, R; Downs, Angela M.; Hamouda, Osamah; Touloumi, Giota; Karafoulidou, Anastasia; Κατσαρού, Όλγα; Donfield, Sharyne; Gomperts, Edward D.; Hilgartner, M. W.; Hoots, Keith; Schoenbaum, Ellie E.; Zangerle, Robert; Amo, Julia del; Pezzotti, Patrizio; Rezza, Giovanni; Hutchinson, S; Gore, S M; Kingsley, Lawrence; Schrager, Lewis K.; Melnick, Sandra; Koblin, Beryl A.; Eskild, Anne; Bruun, JN; Sannes, Mette; Bg, Evans; Lepri, AC; Sabin, Caroline; Buchbinder, Susan; Vittinghoff, Eric; Moss, Andrew R.; Osmond, Dennis; Winkelstein, W; Goldberg, David J.; Boufassa, Faroudy; Meyer, Laurence; Egger, Matthias; Francioli, P.; Rickenbach, Martin; Cooper, David A.; Tindall, Brett; Sharkey, Tyronza; Vizzard, Jeanette; Kaldor, John; Cunningham, Philip; Vanhems, Philippe; Learmont, Jennifer; Farewell,; Berglund, O; Mosley, James W.; Operskalski, Eva A.; Berg, M van den; Metzger, David S.; Tobin, David M.; Woody, George; Rusnak, Janice M.; Hendrix, Craig W.; Garner, Robin; Hawkes, Clifton A.; Renzullo, Philip O.; Garland, Frank C.; Ewart, D. W.; Giangrande, Paul; Lee, C; Phillips, Andrew; Spooner, R. J. D.; Wilde, J. T.; Winter, Mark; Johnson, AM; Lorenzo, JI; Schechter, Mauro; Incubation, Collaborative Grp Aids

doi:10.1016/s0140-6736(00)02061-4

Cited by 379 publications

(19 citation statements)

References 18 publications

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“…First, data comparisons were made based on the availability of drug regimens at different times rather than on the actual use of these treatments. However, many authors has supported and used this approach [2],[18],[33]. Survival analysis studies often use last known contact date as the censoring date for patients with unknown death information, which can lead to overestimation of survival if a significant proportion of patients with lower survival was lost to follow-up.…”

Section: Discussionmentioning

confidence: 99%

Survival of AIDS patients in Sao Paulo-Brazil in the pre- and post-HAART eras: a cohort study

Tancredi¹,

Waldman

2014

BMC Infect Dis

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BackgroundBrazil was the first middle-income country to provide free and universal access to AIDS treatment. Understanding the impact of this policy is key to promote ongoing improvement of current intervention strategies. The aim of this study was to compare mortality rates and survival in a cohort of AIDS patients before and after the introduction of antiretrovirals (ARV) and to investigate predictors of survival.MethodsA retrospective cohort study of AIDS patients aged 13 years or more living in the city of Sao Paulo was conducted. All patients were recruited from an STD/HIV outpatient clinic between 1988 and 2003 and followed up until 2005. We estimated AIDS mortality rates in person-years (py) and carried out a survival analysis using the Kaplan-Meier method. The Cox proportional hazards model was used to assess predictors of survival in AIDS patients.ResultsThe study cohort comprised 6,594 patients. The yearly mean mortality rates were 17.6, 23.2, and 7.8 per 1,000 py for the study periods 1988-1993, 1994-1996, and 1997-2003, respectively. Median survival time was 13.4 and 22.3 months for patients entering the study in the first and second study periods and survival time was 108 months or more in 72% of those entering the study during 1997-2003. Factors independently associated with shorter survival included: AIDS diagnosis during the 1994-1996 (HR 2.0) and 1988-1993 (HR 3.2) periods; 50 years of age or more (HR 2.0); exposure category of injection drug users (IDU) (HR 1.5); 8 years of schooling or less (HR 1.4); no schooling (HR 2.1); and CD4+ counts between 350 and 500 cells/mm3 (HR 1.2) and less than 350 cells/mm3 at AIDS diagnosis (HR 1.3).ConclusionsThe study showed a strong impact following the introduction of HAART in 1996 with decreased AIDS mortality, increased survival rates, and benefits with early introduction of HAART. However, some groups of patients were less likely to benefit from the new drug regimens. Public policies promoting health equity create an enabling environment helping AIDS control programs in developing countries to achieve their goals as effectively as in developed countries.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0599-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Survival of AIDS patients in Sao Paulo-Brazil in the pre- and post-HAART eras: a cohort study

Tancredi¹,

Waldman

2014

BMC Infect Dis

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“…In adult HIV infection, survival times decrease with increasing age at seroconversion, with a median time to AIDS and death of approximately a decade without ART (16). In contrast, mortality among vertically infected children in Africa exceeds 50% by the age of 2 years in the absence of ART (17).…”

Section: Clinical Coursementioning

confidence: 99%

“…Furthermore, lower mortality rates have been observed that the later HIV is acquired postnatally via breastfeeding (20). Interestingly, a cohort of children with hemophilia, who acquired HIV infection between the age of 5 and 14 years, had significantly longer AIDS-free survival times than adults (16). Long-term survival rates in vertically infected untreated children are estimated to be higher than initially appreciated with a probability of 20–30% surviving up to 10 years if infected perinatally and 16 years if infected via breastfeeding (20, 21).…”

Section: Clinical Coursementioning

confidence: 99%

Immunity to HIV in Early Life

2014

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The developing immune system is adapted to the exposure to a plethora of pathogenic and non-pathogenic antigens encountered in utero and after birth, requiring a fine balance between protective immunity and immune tolerance. In early stages of life, this tolerogenic state of the innate and adaptive immune system and the lack of immunological memory render the host more susceptible to infectious pathogens like HIV. HIV pathogenesis is different in children, compared to adults, with more rapid disease progression and a substantial lack of control of viremia compared to adults. Plasma viral load remains high during infancy and only declines gradually over several years in line with immune maturation, even in rare cases where children maintain normal CD4 T-lymphocyte counts for several years without antiretroviral therapy (ART). These pediatric slow progressors also typically show low levels of immune activation despite persistently high viremia, resembling the phenotype of natural hosts of SIV infection. The lack of immunological memory places the fetus and the newborn at higher risk of infections; however, it may also provide an opportunity for unique interventions. Frequencies of central memory CD4+ T-lymphocytes, one of the main cellular reservoirs of HIV, are very low in the newborn child, so immediate ART could prevent the establishment of persistent viral reservoirs and result in “functional cure.” However, as recently demonstrated in the case report of the “Mississippi child” who experienced viral rebound after more than 2 years off ART, additional immunomodulatory strategies might be required for sustained viral suppression after ART cessation. In this review, we discuss the interactions between HIV and the developing immune system in children and the potential implications for therapeutic and prophylactic interventions.

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“…The second stage, chronic asymptomatic infection, ranges in duration from 4 to 12 years (34) and is characterized by steady viral load, a gradual decline in CD4 ϩ T cells, and continued (partially successful) adaptive immune response against HIV. In the absence of treatment, immune compromise permits development of the opportunistic infections and comorbidities that constitute AIDS; the mean time between transmission and AIDS-related death is 10 to 11 years (34,35).…”

Section: Results: the Gene Expression Of Hiv-driven Immunological Damage Hiv Impact On Gene Expression Of Mixed Cell Populationsmentioning

confidence: 99%

Gene Expression: the Key to Understanding HIV-1 Infection?

Judge

Parker

Naniche

et al. 2020

Microbiol Mol Biol Rev

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SUMMARY Gene expression profiling of the host response to HIV infection has promised to fill the gaps in our knowledge and provide new insights toward vaccine and cure. However, despite 20 years of research, the biggest questions remained unanswered. A literature review identified 62 studies examining gene expression dysregulation in samples from individuals living with HIV. Changes in gene expression were dependent on cell/tissue type, stage of infection, viremia, and treatment status. Some cell types, notably CD4+ T cells, exhibit upregulation of cell cycle, interferon-related, and apoptosis genes consistent with depletion. Others, including CD8+ T cells and natural killer cells, exhibit perturbed function in the absence of direct infection with HIV. Dysregulation is greatest during acute infection. Differences in study design and data reporting limit comparability of existing research and do not as yet provide a coherent overview of gene expression in HIV. This review outlines the extraordinarily complex host response to HIV and offers recommendations to realize the full potential of HIV host transcriptomics.

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Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis

Cited by 379 publications

References 18 publications

Survival of AIDS patients in Sao Paulo-Brazil in the pre- and post-HAART eras: a cohort study

Survival of AIDS patients in Sao Paulo-Brazil in the pre- and post-HAART eras: a cohort study

Immunity to HIV in Early Life

Gene Expression: the Key to Understanding HIV-1 Infection?

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