Kaposi’s sarcoma is an angioproliferative tumor caused by human herpesvirus 8 in the context of immunodeficiency, such as that induced by HIV infection or immunosuppressive therapy. Its incidence has ...dramatically fallen in patients living with HIV (PLHIV) since the introduction of potent antiretroviral combinations 25 years ago due to the restoration of immunity and better control of HIV replication. However, KS is still one of the most frequently occurring cancers in PLHIV, in particular in men who have sex with men and in sub-Saharan Africa, where it is still endemic. Even in the context of restored immunity, the risk of KS is still more than 30 times higher in PLHIV than in the general population. Recent evidence indicates that early initiation of antiretroviral treatment, which is recommended by current guidelines, may reduce the risk of KS but it needs to be accompanied by early access to care. This review mainly focuses on the recent epidemiological features of KS in the context of HIV infection.
Summary Background The relative roles of immunodeficiency, HIV viral load, and combination antiretroviral therapy (cART) in the onset of individual cancers have rarely been examined. We examined the ...effect of these factors on the risk of specific cancers in patients infected with HIV-1. Methods We investigated the incidence of both AIDS-defining cancers (Kaposi's sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers (Hodgkin's lymphoma, lung cancer, liver cancer, and anal cancer) in 52 278 patients followed up in the French Hospital Database on HIV cohort during 1998–2006 (median follow-up 4·9 years, IQR 2·1–7·9; 255 353 person-years). We tested 78 models with different classifications of immunodeficiency, viral load, and cART with Poisson regression. Findings Current CD4 cell count was the most predictive risk factor for all malignancies apart from anal cancer. Compared with patients with CD4 count greater than 500 cells per μL, rate ratios (RR) ranged from 1·9 (95% CI 1·3–2·7) for CD4 counts 350–499 cells per μL to 25·2 (17·1–37·0) for counts less than 50 cells per μL for Kaposi's sarcoma (p<0·0001), from 1·3 (0·9–2·0) to 14·8 (9·7–22·6) for non-Hodgkin lymphoma (p<0·0001), from 1·2 (0·7–2·2) to 5·4 (2·4–12·1) for Hodgkin's lymphoma (p<0·0001), from 2·2 (1·3–3·6) to 8·5 (4·3–16·7) for lung cancer (p<0·0001), and from 2·0 (0·9–4·5) to 7·6 (2·7–20·8) for liver cancer (p<0·0001). For cervical cancer, we noted a strong effect of current CD4 (RR 0·7 per log2 , 95% CI 0·6–0·8; p=0·0002). The risk of Kaposi's sarcoma and non-Hodgkin lymphoma increased for current plasma HIV RNA greater than 100 000 copies per mL compared with patients with controlled viral load (RR 3·1, 95% CI 2·3–4·2, p<0·0001; and 2·9, 2·1–3·9, p<0·0001, respectively), whereas cART was independently associated with a decreased incidence (0·3, 0·2–0·4, p<0·0001; and 0·8, 0·6–1·0, p=0·07, respectively). The RR of cervical cancer for those receiving cART was 0·5 (0·3–0·9; p=0·03). The risk of anal cancer increased with the time during which the CD4 count was less than 200 cells per μL (1·3 per year, 1·2–1·5; p=0·0001), and viral load was greater than 100 000 copies per mL (1·2 per year, 1·1–1·4, p=0·005). Interpretation cART would be most beneficial if it restores or maintains CD4 count above 500 cells per μL, thereby indicating an earlier diagnosis of HIV infection and an earlier treatment initiation. Cancer-specific screening programmes need to be assessed in patients with HIV. Funding Agence Nationale de Recherches sur le SIDA et les hépatites (ANRS), INSERM, and the French Ministry of Health.
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.
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.
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.
Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for ...HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers PTCs) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.
The main aim of this study was to determine whether HIV replication can be controlled following interruption of treatment started early in the course of infection (CD4 >350 cells/μl and viral load ...<50 000 copies/ml), but not during the primary infection.
Patients enrolled in a multicenter trial of treatment interruption (ANRS 116 SALTO) with CD4 above 450 cells/μl and viral load below 400 copies/ml at treatment interruption were selected for this second analysis. We determined the proportion of patients whose plasma HIV-RNA load remained below 400 copies/ml during the first 12 months of treatment interruption, and baseline factors predictive of time to loss of viral control. Viral load rebound was defined as two successive values above 400 copies/ml, or as one value above 400 copies/ml, followed by treatment resumption.
We studied 95 patients with a median CD4 nadir of 382 cells/μl (340-492). At treatment interruption, the median CD4 cell count and HIV-DNA load were 813/μl (695-988) and 206 copies/10 peripheral blood mononuclear cells (PBMCs) (53-556). Twelve months after treatment interruption, seven patients still had viral load below 400 copies/ml (Kaplan-Meier estimate 7.5%, 95% confidence interval 3.7-14.6), and four of them still had viral load below 400 copies/ml at 36 months. A multivariable Cox proportional-hazards model showed that time to loss of viral control was more shorter in patients with HIV-DNA at least 150 copies/10 PBMCs at treatment interruption (hazard ratio 2.1, 95% confidence interval 1.3-3.3, P = 0.002) than in those with HIV-DNA below 150 copies/10 PBMCs.
Patients who have low HIV-DNA levels at antiretroviral treatment interruption are more likely to maintain viral control for long periods.
The multicenter national Mortalité 2005 survey aimed at describing the distribution of causes of death among HIV-infected adults in France in 2005 and its changes as compared with 2000.
Physicians ...involved in the management of HIV infection notified deaths and documented the causes using a standardized questionnaire similar to the previous survey performed in 2000.
Overall, 1042 deaths were notified in 2005 (vs 964 in 2000): with median age, 46 years (vs 41 years); men, 76%; and median last CD4 cell count, 161/mm (vs 94). The proportion of underlying causes of death due to AIDS decreased (36% in 2005 vs 47% in 2000), and the proportion of cancer not related to AIDS or hepatitis (17% vs 11%), liver related disease (15% vs 13%: hepatitis C, 11%, and hepatitis B, 2%), cardiovascular disease (8% vs 7%), or suicide (5% vs 4%) increased. Among the 375 AIDS-related deaths, the most frequent event was non-Hodgkin lymphoma (28%). Among cancers not related to AIDS or hepatitis, the most frequent localizations were lung (31%) and digestive tract (14%). Among the 154 liver-related deaths, 24% were due to hepatocarcinoma.
The heterogeneity of causes of death among HIV-infected adults was confirmed and intensified in 2005, with 3 causes following AIDS: cancers and liver-related and cardiovascular diseases.
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.
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.
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.
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.
Tuberculosis (TB) is a public health problem in Lithuania, among the 18 high-priority TB countries in the European region, and the most common AIDS-indicative disease with the highest proportion in ...the EU/EEA since 2015. The study aimed to identify socio-demographic, clinical characteristics and their relationship with TB outcomes in TB-HIV co-infected patients in Lithuania.
A retrospective chart review analysed the characteristics of TB-HIV co-infected adults registered in State Information System of Tuberculosis over 2008-2020. The factors associated with drug-resistant TB and unsuccessful treatment outcome were identified by multivariable logistic regression.
The study included 345 cases in 311 patients (239 new, 106 previously treated cases), median age 40 years (IQR 35-45), 80.7% male. 67.8% patients knew their HIV-positive status before TB diagnosis, median time to TB diagnosis was 8 years (IQR 4-12). 83.6% were unemployed, 50.5%-anytime intravenous drug users (IDU), 34.9% abused alcohol. Drug-resistant TB rates in new and previously treated TB cases were 38.1% and 61.3%, respectively. In multivariable analysis, higher risk of drug-resistant TB was associated with imprisonment in new (aOR 3.35; 95%CI 1.17-9.57) and previously treated (aOR 6.63; 95%CI 1.09-40.35) cases. In 52.3% of new TB cases and in 42.5% previously treated TB cases the treatment outcomes were unsuccessful. In multivariable analysis of new TB cases, current imprisonment (aOR 2.77; 95%CI 1.29-5.91) and drug-resistant TB (aOR 2.18; 95%CI 1.11-4.28) were associated with unsuccessful treatment outcome. In multivariable analysis of previously treated TB cases, female gender (aOR 11.93; 95%CI 1.86-76.69), alcohol abuse (aOR 3.17; 95%CI 1.05-9.58), drug-resistant TB (aOR 4.83; 95%CI 1.53-15.28) were associated with unsuccessful treatment outcome.
In the TB-HIV-infected adult cohort in Lithuania, unemployment, imprisonment, IDU, alcohol abuse, known to be risk factors for TB, were very frequent. Drug resistance was an undeniable risk factor for unsuccessful treatment outcome and imprisonment was associated with drug resistant TB.
We studied the frequency and risk factors for loss of long-term non-progressor (LTNP) and HIV controller (HIC) status among patients identified as such in 2005 in the French Hospital Database on HIV ...(FHDH-ANRS CO4).
We selected patients who were treatment-naïve and asymptomatic in 2005 (baseline). Those with ≥8 years of known HIV infection and a CD4 cell nadir ≥500/mm3 were classified as LTNP and those with ≥10 years of known HIV infection and 90% of plasma viral load (VL) values ≤500 copies/ml in the absence of cART as HIC. cART initiation without loss of status and death from non AIDS-defining causes were considered as competing events.
After 5 years of follow-up, 33% (95%CI; 27-42) of 171 LTNP patients and 17% (95%CI; 10-30) of 72 HIC patients had lost their status. In multivariable analyses, loss of LTNP status was associated with lower baseline CD4 cell counts and CD4/CD8 ratios. Only VL was significantly associated with loss of HIC status after adjustment for the baseline CD4 cell count, the CD4/CD8 ratio, and concomitant LTNP status. The hazard ratio for loss of HIC status was 5.5 (95%CI, 1.5-20.1) for baseline VL 50-500 vs ≤50 cp/mL, after adjustment for the baseline CD4 cell count.
One-third of LTNP and one-fifth of HIC patients lost their status after 5 years of follow-up, raising questions as to the possible benefits and timing of ART initiation in these populations.
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