Clinical Progression Rates by CD4 Cell Category Before and After the Initiation of Combination Antiretroviral Therapy (cART)

OBJECTIVE: Rates of AIDS defining event (ADE), serious ADE and death by CD4 and HIV RNA categories before and after combination antiretroviral therapy (cART) initiation are lacking for high CD4 counts. METHODS: Event rates were estimated within CD4 cell strata using a Poisson regression model adjusting for sex, exposure category, age, and current HIV RNA (<4, 4-4.99, > or =5 log copies/ml), and including an interaction term between the CD4 cell count and cART indicator. RESULTS: 7317 and 6376 persons contributed to "naïve " and "cART " groups respectively, of whom 3911 contributed to both. At the same CD4 level, the risk of ADE was nearly 2 fold higher during naive follow-up compared to cART for CD4 <500 cells/mm(3). However, after adjustment for current HIV RNA, the risk of ADE became similar for both groups except for CD4 count <200 cells/mm(3) when it is 35% (6-72%) higher for naives. The same results were observed for the risk of serious ADE. There was no evidence of a difference in risk of death between naive and cART follow-up at specific CD4 categories even after adjustment for HIV RNA. CONCLUSION: Within CD4 cell strata above 200 cells/mm(3), the risk of ADE before ART initiation is higher than it is following cART initiation

Incidence of HIV-related anal cancer remains increased despite long-term combined antiretroviral treatment: results from the french hospital database on HIV.

PURPOSE: To study recent trends in the incidence of anal cancer in HIV-infected patients receiving long-term combined antiretroviral treatment (cART) compared with the general population. PATIENTS AND METHODS: From the French Hospital Database on HIV, we identified 263 cases of invasive anal squamous cell carcinoma confirmed histologically between 1992 and 2008. We compared incidence rates of anal cancer across four calendar periods: 1992-1996 (pre-cART period), 1997-2000 (early cART period), and 2001-2004 and 2005-2008 (recent cART periods). Standardized incidence ratios (SIRs) were calculated by using general population incidence data from the French Network of Cancer Registries. RESULTS: In HIV-infected patients, the hazard ratio (HR) in the cART periods versus the pre-cART period was 2.5 (95% CI, 1.28 to 4.98). No difference was observed across the cART calendar periods (HR, 0.9; 95% CI, 0.6 to 1.3). In 2005-2008, HIV-infected patients compared with the general population had an excess risk of anal cancer, with SIRs of 109.8 (95% CI, 84.6 to 140.3), 49.2 (95% CI, 33.2 to 70.3), and 13.1 (95% CI, 6.8 to 22.8) for men who have sex with men (MSM), other men, and women, respectively. Among patients with CD4 cell counts above 500/μL for at least 2 years, SIRs were 67.5 (95% CI, 41.2 to 104.3) when the CD4 nadir was less than 200/μL for more than 2 years and 24.5 (95% CI, 17.1 to 34.1) when the CD4 nadir was more than 200/μL. CONCLUSION: Relative to that in the general population, the risk of anal cancer in HIV-infected patients is still extremely high, even in patients with high current CD4 cell counts. cART appears to have no preventive effect on anal cancer, particularly in MSM

Epidemiology of the anal cancer

Le cancer anal est un cancer rare. Sa fréquence est très inférieure à celle des cancers colorectaux puisqu’il ne représente que 3 % de l’ensemble des cancers de la partie basse du tube digestif. Dans la population générale, le cancer de l’anus est plus fréquent chez les femmes que chez les hommes et survient très généralementaprès 60 ans. L’infection à Human Papilloma Virus (HPV) est lefacteur étiologique le plus important avec l’immunodépression quifavorise la transformation maligne des dysplasies anales induitespar l’infection HPV. La population infectée par le VIH, etsingulièrement les patients homosexuels, sont plus à risque de cancer anal que la population générale. En France, l’incidence du cancer anal a été récemment estimée à 1,4/100000 personnes/année (PA) en population générale, à 56,3/100 000 PA dans la population infectée par le VIH et à 95,0/100000 PA dans le sous-groupe des homosexuels masculins VIH+. Un tel sur-risque justifie de mettre en place un dépistage systématique dans la population infectée par le VIH d’autant plus que les combinaisons antirétrovirales semblent sans effet sur le risque d’apparition du cancer anal.Anal cancer is a rare tumor that represents 3 % of all cancer of the lower gastrointestinal tract. In the general population, anal cancer is more frequent in women than in men and usually arises after 60 years. Human Papilloma Virus infection is the most important etiologic factor together with immunodepression that facilitates the malignant transformation of HPV-induced anal dysplasia. In France, the incidence of anal cancer has been estimated to 1.4/100000 person-years (PY) in the general population and to 56.3/100000 PY in HIV-infected patients. This increased risk is in favor of adapting surveillance and screening programs for HIV-infected patients especially since combined antiretroviral therapy does not seem to have any impact on the risk of anal cancer occurrence

Do tests devised to detect recent HIV-1 infection provide reliable estimates of incidence in Africa?

International audienceThe objective of this study was to assess the performance of 4 biologic tests designed to detect recent HIV-1 infections in estimating incidence in West Africa (BED, Vironostika, Avidity, and IDE-V3). These tests were assessed on a panel of 135 samples from 79 HIV-1-positive regular blood donors from Abidjan, C?d'Ivoire, whose date of seroconversion was known (Agence Nationale de Recherches sur le SIDA et les H?tites Virales 1220 cohort). The 135 samples included 26 from recently infected patients (180 days), and 15 from patients with clinical AIDS. The performance of each assay in estimating HIV incidence was assessed through simulations. The modified commercial assays gave the best results for sensitivity (100% for both), and the IDE-V3 technique gave the best result for specificity (96.3%). In a context like Abidjan, with a 10% HIV-1 prevalence associated with a 1% annual incidence, the estimated test-specific annual incidence rates would be 1.2% (IDE-V3), 5.5% (Vironostika), 6.2% (BED), and 11.2% (Avidity). Most of the specimens falsely classified as incident cases were from patients infected for >180 days but <1 year. The authors conclude that none of the 4 methods could currently be used to estimate HIV-1 incidence routinely in C?d'Ivoire but that further adaptations might enhance their accuracy

Blunted Response to Combination Antiretroviral Therapy in HIV Elite Controllers: An International HIV Controller Collaboration

Objective: HIV “elite controllers” (ECs) spontaneously control viral load, but some eventually require combination antiretroviral treatment (cART), due to a loss of viral control or a decline in CD4 T-cell counts. Here we studied the CD4 T-cell count dynamics after cART initiation among 34 ECs followed in U.S. and European cohorts, by comparison with chronically viremic patients (VIRs). Methods: ECs were defined as patients with at least ≥5 viral load (VL) measurements below 400 copies/mL during at least a 5-year period despite never receiving ART and were selected from the French ANRS CO18 cohort, the U.S. SCOPE cohort, the International HIV Controllers study and the European CASCADE collaboration. VIRs were selected from the ANRS COPANA cohort of recently-diagnosed (<1 year) ART-naïve HIV-1-infected adults. CD4 T-cell count dynamics after cART initiation in both groups were modelled with piecewise mixed linear models. Results: After cART initiation, CD4 T-cell counts showed a biphasic rise in VIRs with: an initial rapid increase during the first 3 months (+0.63/month), followed by +0.19/month. This first rapid phase was not observed in ECs, in whom the CD4Tc count increased steadily, at a rate similar to that of the second phase observed in VIRs. After cART initiation at a CD4 T-cell count of 300/mm3, the estimated mean CD4 T-cell gain during the first 12 months was 139/mm3 in VIRs and 80/mm3 in ECs (p = 0.048). Conclusions: cART increases CD4 T-cell counts in elite controllers, albeit less markedly than in other patients

Beyond viral suppression of HIV - the new quality of life frontier

BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV-related discrimination. We propose adding a 'fourth 90' to the testing and treatment target: ensure that 90 % of people with viral load suppression have good health-related quality of life. The new target would expand the continuum-of-services paradigm beyond the existing endpoint of viral suppression. Good health-related quality of life for PLHIV entails attention to two domains: comorbidities and self-perceived quality of life. CONCLUSIONS: Health systems everywhere need to become more integrated and more people-centered to successfully meet the needs of virally suppressed PLHIV. By doing so, these systems can better meet the needs of all of their constituents - regardless of HIV status - in an era when many populations worldwide are living much longer with multiple comorbidities