AIDS-related Mortality Research Articles

Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta-analysis.

The advent of antiretroviral therapy has significantly improved AIDS-related morbidity and mortality. Yet, among people living with HIV, deaths due to non-AIDS-defining illnesses have been on the rise. The objective of this study was to provide information about the global prevalence and distribution of non-AIDS causes of death in the last ten years among people living with HIV receiving antiretroviral therapy, by income levels of countries. We used broad search terms in Google Scholar, PubMed, and EMBASE to identify all studies that investigated the cause of death among people living with HIV receiving antiretroviral therapy, published after January 1, 2005. References were also identified from review articles and reference lists. Inclusion criteria were English language, the study's end date was after 2005, all patients were HIV-positive, at least two-thirds of the patients were receiving antiretroviral therapy, at least one patient died of non-AIDS causes of death. Titles, abstracts, and articles were reviewed by at least two independent readers. Of 2951 titles identified in our original search, 151 articles were selected for further screening. We identified 19 studies meeting our full criteria, with patients from 55 different nations. Pooled non-AIDS causes of death prevalence estimates in high-income countries were 53.0% (95% confidence interval, 43.6-62.3), in developing countries 34.0% (95% confidence interval, 20.3-49.1), and in sub-Saharan countries 18.5% (95% confidence interval, 13.8-23.7). Statistically significant variation was noted within and between categories. Our findings show that a significant number of people living with HIV across the world die from cardiovascular disease, non-AIDS malignancies, and liver disease. There is a global need for further scrutiny in all regions to improve preventive measures and early detection according to distinct causes of death patterns.

Effect of subsequent pregnancies on HIV disease progression among women in the Mulago Hospital MTCT-Plus program in Uganda

To investigate the effect of subsequent pregnancies on HIV disease progression among HIV-infected women at Mulago Hospital, Uganda. In a retrospective cohort study, data were analyzed from women enrolled in the Mother-To-Child Transmission Plus program from March 2003 to December 2011. The CD4 cell count, the development of new AIDS-defining opportunistic infections, and the AIDS-related mortality were compared between women with and without subsequent pregnancies. Overall, 409 women were enrolled and 195 (47.7%) had subsequent pregnancies. Antiretroviral therapy (ART) was initiated in 143 (73.3%) women with and 155 (72.4%) women without subsequent pregnancies. Kaplan-Meier analysis for women receiving ART showed no differences between women with and without subsequent pregnancies in the median times to clinical failure (62.7 vs 64.7 months; P=0.31), immunological failure (68.8 vs 75.5 months; P=0.10), and death (68.8 vs 75.5 months; P=0.53). In a Cox regression analysis, subsequent pregnancies were not associated with immunological failure during follow-up (adjusted hazard ratio 1.13, 95% confidence interval 0.06-2.09). Subsequent pregnancies could have no detrimental effect on HIV disease progression among HIV-infected women whose treatment is well managed.

Are there differences in disease progression and mortality among male and female HIV patients on antiretroviral therapy? A meta-analysis of observational cohorts

ABSTRACTStudies examining the sex differences in morbidity and mortality among HIV/AIDS patients have yielded inconsistent results. We conducted a meta-analysis of sex differences in disease progression and mortality among HIV/AIDS patients. Medical literature databases from inception to August 2014 were searched for published observational studies assessing sex differences in immunologic and virologic response, disease progression and mortality among HIV-infected patients. Random effects meta-analyses of 115 eligible studies were conducted to obtain pooled estimates of outcomes and heterogeneity was explored in sub-group analyses. Pooled estimates showed an increased risk of progression to AIDS (relative risk [RR]=1.11,95% CI=1.02–1.21) and all-cause mortality (RR=1.23, 95% CI=1.17–1.29) among males compared to females. All-cause mortality differed by sex only in low and middle income countries. The risk of AIDS-related mortality (RR=1.03, 95% CI=0.82–1.30), immunologic failure (RR=1.19,95% CI: 0.97–1.47), virologic suppression (RR=0.98, 95% CI=0.84–1.14), virologic failure (RR=1.26, 95% CI=0.99–1.61) and the change in CD4 cell count (Weighted mean difference [WMD] = −5.15, 95% CI= −13.57 to 3.28) did not differ by sex. These findings were modified by disease severity, adherence and use of highly active antiretroviral therapy. We conclude that HIV-related disease progression and survival outcomes are poorer in males.

Causes of Death among AIDS Patients after Introduction of Free Combination Antiretroviral Therapy (cART) in Three Chinese Provinces, 2010-2011.

IntroductionAlthough AIDS-related deaths have had significant economic and social impact following an increased disease burden internationally, few studies have evaluated the cause of AIDS-related deaths among patients with AIDS on combination anti-retroviral therapy (cART) in China. This study examines the causes of death among AIDS-patients in China and uses a methodology to increase data accuracy compared to the previous studies on AIDS-related mortality in China, that have taken the reported cause of death in the National HIV Registry at face-value.MethodsDeath certificates/medical records were examined and a cross-sectional survey was conducted in three provinces to verify the causes of death among AIDS patients who died between January 1, 2010 and June 30, 2011. Chi-square analysis was conducted to examine the categorical variables by causes of death and by ART status. Univariate and multivariate logistic regression were used to evaluate factors associated with AIDS-related death versus non-AIDS related death.ResultsThis study used a sample of 1,109 subjects. The average age at death was 44.5 years. AIDS-related deaths were significantly higher than non-AIDS and injury-related deaths. In the sample, 41.9% (465/1109) were deceased within a year of HIV diagnosis and 52.7% (584/1109) of the deceased AIDS patients were not on cART. For AIDS-related deaths (n = 798), statistically significant factors included CD4 count <200 cells/mm3 at the time of cART initiation (AOR 1.94, 95%CI 1.24–3.05), ART naïve (AOR 1.69, 95%CI 1.09–2.61; p = 0.019) and age <39 years (AOR 2.96, 95%CI 1.77–4.96).ConclusionFor the AIDS patients that were deceased, only those who initiated cART while at a CD4 count ≥200 cells/mm3 were less likely to die from AIDS-related causes compared to those who didn’t initiate ART at all.

Hit me with your best shot: dolutegravir - a space in the next WHO guidelines?

Hit me with your best shot: dolutegravir - a space in the next WHO guidelines?

Impact of cocaine abuse on HIV pathogenesis.

Over 1.2 million people in the United States are infected with the human immunodeficiency virus type 1 (HIV-1). Tremendous progress has been made over the past three decades on many fronts in the prevention and treatment of HIV-1 disease. However, HIV-1 infection is incurable and antiretroviral drugs continue to remain the only effective treatment option for HIV infected patients. Unfortunately, only three out of ten HIV-1 infected individuals in the US have the virus under control. Thus, majority of HIV-1 infected individuals in the US are either unaware of their infection status or not connected/retained to care or are non-adherent to antiretroviral therapy (ART). This national public health crisis, as well as the ongoing global HIV/AIDS pandemic, is further exacerbated by substance abuse, which serves as a powerful cofactor at every stage of HIV/AIDS including transmission, diagnosis, pathogenesis, and treatment. Clinical studies indicate that substance abuse may increase viral load, accelerate disease progression and worsen AIDS-related mortality even among ART-adherent patients. However, confirming a direct causal link between substance abuse and HIV/AIDS in human patients remains a highly challenging endeavor. In this review we will discuss the recent and past developments in clinical and basic science research on the effects of cocaine abuse on HIV-1 pathogenesis.

High Prevalence of HIV Low Abundance Drug-Resistant Variants in a Treatment-Naive Population in North Rift Kenya.

The advent of antiretroviral treatment (ART) has resulted in a dramatic reduction in AIDS-related morbidity and mortality. However, the emergence and spread of antiretroviral drug resistance (DR) threaten to negatively impact treatment regimens and compromise efforts to control the epidemic. It is recommended that surveillance of drug resistance occur in conjunction with scale-up efforts to ensure that appropriate first-line therapy is offered relative to the resistance that exists. However, standard resistance testing methods used in Sub-Saharan Africa rely on techniques that do not include low abundance DR variants (LADRVs) that have been documented to contribute to treatment failure. The use of next generation sequencing (NGS) has been shown to be more sensitive to LADRVS. We have carried out a preliminary investigation using NGS to determine the prevalence of LDRVS among a drug-naive population in North Rift Kenya. Antiretroviral-naive patients attending a care clinic in North Rift Kenya were requested to provide and with consent provided blood samples for DR analysis. DNA was extracted and amplified and nested PCR was conducted on the pol RT region using primers tagged with multiplex identifiers (MID). Resulting PCR amplicons were purified, quantified, and pyrosequenced using a GS FLX Titanium PicoTiterPlate (Roche). Valid pyrosequencing reads were aligned with HXB-2 and the frequency and distribution of nucleotide and amino acid changes were determined using an in-house Perl script. DR mutations were identified using the IAS-USA HIV DR mutation database. Sixty samples were successfully sequenced of which 26 were subtype A, 9 were subtype D, 2 were subtype C, and the remaining were recombinants. Forty-six (76.6%) had at least one drug resistance mutation, with 25 (41.6%) indicated as major and the remaining 21 (35%) indicated as minor. The most prevalent mutation was NRTI position K219Q/R (11/46, 24%) followed by NRTI M184V (5/46, 11%) and NNRTI K103N (4/46, 9%). Our use of NGS technology revealed a high prevalence of LADRVs among drug-naive populations in Kenya, a region with predominantly non-B subtypes. The impact of these mutations on the clinical outcome of ART can be ascertained only through long-term follow-up.

Drug Resistance Testing in HIV Infected Individuals on Treatment and Naive: Implications on Treatment Outcome

Background: The Government of Kenya started offering ART in the public sector since 2003. Despite the dramatic reduction in AIDS related morbidity and mortality, the emergence and spread of drug resistance (DR) threatens to negatively impact on treatment regimens and compromise efforts to control the epidemic. Therefore, there is a need for information on the situation of DR Mutations (DRMS) and their implications on treatment.

Predictors of progression to AIDS and mortality post-HIV infection: a long-term retrospective cohort study

This study was conducted to better understand the prognostic factors influencing the disease progression and mortality in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) in a high–middle-income country. This registry-based retrospective cohort study was conducted in Tehran from April 2004 to March 2014. We enrolled 2473 HIV-infected patients who had a medical record in Behavioral Diseases Counseling Centers. The outcomes of interest were the estimation of time: (1) from HIV diagnosis to AIDS progression and (2) from AIDS to AIDS-related death. The 1-year, 5-year, and 10-year probability of disease progression from HIV diagnosis to AIDS was 45.0%, 69.9%, and 90.4%, and that of AIDS-related death was 17.2%, 30.3%, and 39.2%, respectively. Multivariate Cox regression analysis indicated that AIDS progression was significantly associated with male sex (P = 0.022), an increase in age (P = 0.001), low educational levels (P = 0.001), and a decreased level of CD4 cell count (P = 0.001). Furthermore, the AIDS-related mortality was significantly associated with male sex (P = 0.010), tuberculosis coinfection (P = 0.001), and antiretroviral therapy (P = 0.001). The results of this study indicated that progression to AIDS and AIDS-related death is affected by several modifiable and non-modifiable predictors. We indicated that a substantial proportion of the HIV-positive people were unaware of their status and were diagnosed very late. This hidden source of HIV infection had the opportunity to transmit the infection to other people.

Time to Improve the Global Human Immunodeficiency Virus/AIDS Care Continuum for Adolescents: A Generation at Stake.

Time to Improve the Global Human Immunodeficiency Virus/AIDS Care Continuum for Adolescents: A Generation at Stake.

An Analysis of Prescription Patterns and Incidence of Dyslipidemia in a Korean Tertiary Hospital HIV Patients Receiving High Active Antiretroviral Therapy

Highly active antiretroviral therapy (HAART) has reduced AIDS-related morbidity and mortality; however, it has been associated with metabolic abnormalities including dyslipidemia and dysglycemia depending on the regimens used. The aims of this study were to analyze the prescription patterns of antiretroviral agents and to examine the prevalence of lipid abnormalities among the prescriptions of HAART. The electronic medical records (EMR) of HIV patients were ret- rospectively reviewed from January 2007 to September 2012 based on our inclusion criteria. The patients who had taken HAART for at least 3 months were included in this study. The lipid profiles of patients on antiretrovirals (ARTs) were col- lected from his or her laboratory data, and dyslipidemia was defined as total cholesterol (TC) ≥240 mg/dL and triglycerides (TG) >200 mg/dL. Eighty-four prescriptions were discovered during the study period. Twenty-three prescriptions were the combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhib- itor (NNRTI). Fifty-three prescriptions were the combination of two NRTIs and one protease inhibitor (PI) and thirty-nine prescriptions of them included a PI booster. Eight prescriptions were the combination of two NRTIs and one integrase inhib- itor. The Incidence of hypertriglyceridemia among the patients receiving HAART was totally about 41.7% (2NRTIs+PI reg- imen vs. 2NRTIs+NNRTI regimen vs. 2 NRTIs+integrase inhibitor regimen, 52% vs. 12.5% vs. 25%), but there was no incidence of hypercholesterolemia. This study investigated that the prescription medication patterns and dyslipidemia asso- ciated with lipid abnormalities among HIV patients receiving HAART. The types of HAART prescription regimens had an effect on the occurrence of hypertriglycemia. Further studies related to metabolic abnormalities and adverse effects of HIV patients on ARTs are needed in the near future.

Epidemiological Trends for HIV in Southern Africa: Implications for Reaching the Elimination Targets.

Southern Africa is the region worst affected by HIV in the world and accounts for one third of the global burden of HIV. Achieving the UNAIDS 90-90-90 target by 2020 and ending the AIDS epidemic by 2030 depend on success in this region. We review epidemiological trends in each country in southern Africa with respect to the prevalence, incidence, mortality, coverage of anti-retroviral therapy (ART) and TB notification rates, to better understand progress in controlling HIV and TB and to determine what needs to be done to reach the UNAIDS targets. Significant progress has been made in controlling HIV. In all countries in the region, the prevalence of HIV in people not on ART, the incidence of HIV, AIDS-related mortality and, in most countries, TB notification rates, are falling. In some countries, the risk of infection began to fall before biomedical interventions such as ART became widely available as a result of effective prevention measures or people's awareness of, and response to, the epidemic but the reasons for these declines remain uncertain. Some countries have achieved better levels of ART coverage than others, but all are in a position to reach the 2020 and 2030 targets if they accelerate the roll-out of ART and of targeted prevention efforts. Achieving the HIV treatment targets will further reduce the incidence of HIV-related TB, but efforts to control TB in HIV-negative people must be improved and strengthened.

Improvement of HAART in Brazil, 1998-2008: a nationwide assessment of survival times after AIDS diagnosis among men who have sex with men.

BackgroundIn 1996, Brazil became the first developing country to provide free, universal access to HAART, laboratory monitoring, and clinical care to any eligible patient. As of June 2014, approximately 400,000 patients were under treatment, making it the most comprehensive HIV treatment initiative implemented thus far in a middle-income country, worldwide. The Brazilian epidemic is highly concentrated among men who have sex with men (MSM).MethodsFour national information systems were combined and Cox regression was used to conduct retrospective cohort analysis of HAART availability/access on all-cause mortality among MSM diagnosed with AIDS reported to the information systems between 1998–2008, adjusting for demographic, clinical, and behavioral factors and controlling for spatially-correlated survival data by including a frailty effect. Multiple imputation by chained equations was used to handle missing data.ResultsAmong 50,683 patients, 10,326 died during the 10 year of period. All-cause mortality rates declined following introduction of HAART, and were higher among non-white patients and those starting HAART with higher viral load and lower CD4 counts. In multivariable analysis adjusted for race, age at AIDS diagnosis, and baseline CD4 cell count, MSM diagnosed in latter periods had almost a 50% reduction in the risk of death, compared to those diagnosed between 1998–2001 (2002–2005 adjHR: 0.54, 95% CI:0.51-0.57; 2006–2008 adjHR: 0.51, 95% CI:0.48-0.55). After controlling for spatially correlated survival data, mortality remained higher among those diagnosed in the earliest diagnostic cohort and lower among non-white patients and those starting HAART with higher viral load and lower CD4 lymphocyte counts.ConclusionsUniversal and free access to HAART has helped achieve impressive declines in AIDS mortality in Brazil. However, after a 10-years follow-up, differential AIDS-related mortality continue to exist. Efforts are needed to identify and eliminate these health disparities, therefore improving the Brazilian response towards HIV/AIDS epidemic.

Mortalidad temprana por sida en México durante el periodo 2008-2012

Objetivo. Describir la distribución de la mortalidad por sida (2008-2012) en usuarios de unidades de atención de la Secretaría de Salud de México, en el Sistema de Administración, Logística y Vigilancia de Antirretrovirales (SALVAR). Material y métodos. Análisis descriptivo del tipo de mortalidad y el perfil clínico y sociodemográfico relacionado, de 41 847 pacientes registrados en el SALVAR. Resultados. Se identificaron 3 195 (8.1%) pacientes que fallecieron en el periodo de estudio, de los cuales 59% murió durante los primeros seis meses de seguimiento en el sistema. De éstos, 87.3% fue diagnosticado de manera tardía de acuerdo con su nivel de CD4 inicial (CD4&lt;200 cel/ml3). Conclusión. Los hallazgos resaltan la importancia de fortalecer los programas de detección oportuna y la vinculación efectiva al tratamiento de las personas VIH positivas, como un componente fundamental de la política de acceso universal a tratamiento antirretroviral en México.

A qualitative study of patient motivation to adhere to combination antiretroviral therapy in South Africa.

Taken as prescribed, that is, with high adherence, combination antiretroviral therapy (ART) has changed HIV infection and disease from being a sure predictor of death to a manageable chronic illness. Adherence, however, is difficult to achieve and maintain. The CAPRISA 058 study was conducted between 2007 and 2009 to test the efficacy of individualized motivational counselling to enhance ART adherence in South Africa. As part of the overall trial, a qualitative sub-study was conducted, including 30 individual interviews and four focus group discussions with patients in the first 9 months of ART initiation. Data were inductively analyzed, using thematic analysis, to identify themes central to ART adherence in this context. Four themes emerged that characterize the participants' experiences and high motivation to adhere to ART. Participants in this study were highly motivated to adhere, as they acknowledged that ART was 'life-giving', in the face of a large amount of morbidity and mortality. They were further supported by techniques of routine remembering, and highlighted the importance of good social support and access to supportive healthcare workers, to their continued success in negotiating their treatment. Participants in the current study told us that their adherence motivation is enhanced by free accessible care, approachable and supportive healthcare workers, broad social acceptance of ART, and past first-hand experiences with AIDS-related co-morbidity and mortality. Programs that include specific attention to these aspects of care will likely be successful in the long term.

AIDS incidence and AIDS-related mortality in British Columbia, Canada, between 1981 and 2013: a retrospective study

Appropriate use of highly active antiretroviral therapy (ART) can substantially decrease the risk of progression to AIDS and of premature mortality. We aimed to characterise the trends between 1981 and 2013 in AIDS-defining illnesses (ADIs) and the number AIDS-related deaths in British Columbia, Canada, where ART has been fully subsidised since 1996. We included data on HIV-positive individuals, aged 19 years or older, from four administrative databases in British Columbia: the British Columbia Centre for Excellence in HIV/AIDS, St Paul's Hospital, the British Columbia Vital Statistics Agency, the British Columbia Cancer Agency. We estimated the relative risk of developing an ADI over time by use of a negative binomial model, and we investigated trends in the proportion of all deaths associated with AIDS by use of generalised additive models. Data were available for 3550 people with HIV. 6205 ADIs were recorded. In 2013, 84 ADIs occurred, the lowest number since 1990. The peak of the AIDS epidemic in the region happened in 1994 with 696 ADIs reported (42 ADIs per 100 person-years). Since 1997, the number of ADIs decreased from 253 (7 per 100 person-years) to 84 cases in 2013 (1 per 100 person-years; p<0·0001 for trend in number of ADIs). We have also shown that of 22 ADIs included, only Pneumocystis jirovecii pneumonia remained prominent (albeit with much reduced overall prevalence). 2828 deaths were from AIDS-related causes, peaking in 1996 with 241 (96%) of 252 deaths in people with HIV and declining to 44 (20%) of 218 in 2013. Our results provide further evidence that integrated comprehensive free programmes that facilitate testing and deliver treatment and care can be eff ective in decreasing AIDS-related morbidity and mortality, thus suggesting that control of and eventually an end to AIDS are possible.

HIV-1 transmitted drug resistance and genetic diversity among patients from Piauí State, Northeast Brazil.

HIV-1 transmitted-drug-resistance and genetic diversity are dynamic and may differ in distinct locations/risk groups. In Brazil, increased AIDS incidence and related mortality have been detected in the Northeast region, differently from the epicenter in the Southeast. This cross-sectional study describes transmitted-dru- resistance and HIV-1 subtypes in protease/PR and reverse transcriptase/RT regions among antiretroviral naïve patients from Piauí State, Northeast Brazil. Among 96 patients recruited 89 (92.7%) had HIV-1 PR/RT regions sequenced: 44 females and 45 males, 22 self-declared as men who have sex with men. Transmitted-drug-resistance was investigated by CPR tool (Stanford HIV-1 Drug Resistance/SDRM). HIV-1 subtypes were assigned by REGA and phylogenetic inference. Overall, transmitted-drug-resistance rate was 11.2% (10/89; CI 95%: 5.8-19.1%); 22.7% among men who have sex with men (5/22; CI 95%: 8.8-43.4%), 10% in heterosexual men (2/20; CI 95%: 1.7-29.3%) and 6.8% in women (3/44; CI 95%: 1.8-17.4%). Singleton mutations to protease-inhibitor/PI, nucleoside-reverse-transcriptase-inhibitor/NRTI or non-nucleoside-reverse-transcriptase-inhibitor/NNRTI predominated (8/10): PI mutations (M46L, V82F, L90M); NRTI mutations (M41L, D67N) and NNRTI mutations (K103N/S). Dual class resistance mutations to NRTI and NNRTI were observed: T215L (NRTI), Y188L (NNRTI) and T215N (NRTI), F227L (NNRTI). Subtype B prevailed (86.6%; 77/89), followed by subtype F1 (1.1%, 1/89) and subtype C (1.1%, 1/89). B/F1 and B/C intersubtype recombinants represented 11.2% (10/89). In Piauí State extensive testing of incidence and transmitted-drug-resistance in all populations with risk behaviors may help control AIDS epidemic locally.

HIV and the Millennium Development Goals.

Millennium Development Goal (MDG) 6 has two HIV/AIDS commitments: to have halted and begun to reverse the spread of HIV/AIDS by 2015 and to ensure access to treatment among all those in need by 2010. Given the almost universal lack of access to HIV testing, prevention and treatment for children in high prevalence countries in 2000, the achievements of the past 15 years have been extraordinary, fuelled by massive donor investment, strong political commitment and ambitious global targets; however, MDG 6 is some way from being attained. Prevention of mother-to-child transmission (PMTCT) services have expanded enormously, with new infections among children falling by 58% between 2002 and 2013. There has been a shift towards initiation of lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women, although low HIV testing rates in pregnancy, suboptimal PMTCT coverage and poor retention in care remain barriers to achieving HIV elimination among children. Early infant diagnosis has expanded substantially but, in 2013, only 44% of all HIV-exposed infants were tested before 2 months of age. Diagnosis of HIV, therefore, frequently occurs late, leading to delays in ART initiation. By the end of 2013, approximately 760 000 children were receiving ART, leading to 40% decline in AIDS-related mortality. However, only 24% of HIV-infected children were receiving ART, compared with 36% of adults, leading to a 'treatment gap'. In this review, we summarise progress and remaining challenges in reaching MDG 6 and discuss future strategies to achieve the ambitious goals of paediatric HIV elimination and universal access to treatment.

HIV Treatment for Alcohol and Non-Injection Drug Users in El Salvador.

Since the mid-1990 s, many developing countries have introduced and expanded the availability of combination antiretroviral therapy (cART) to persons living with HIV (PLH). However, AIDS-related mortality continues to be high particularly among drug users. In this article, we present results from in-depth interviews with 13 HIV medical providers and 29 crack cocaine and alcohol using PLH in El Salvador. Providers endorsed negative attitudes toward substance using PLH and warned PLH that combining cART with drugs and alcohol would damage their livers and kidneys resulting in death. Upon diagnosis, PLH received little information about HIV treatment and many suffered depression and escalated their drug use. PLH reported suspending cART when they drank or used drugs because of providers' warnings. Substance using PLH were given few strategies and resources to quit using drugs. Messages from medical providers discourage drug users from initiating or adhering to antiretroviral therapy (ART) and may contribute to treatment abandonment.

Combined Antiretroviral Therapy (cART) Reduces AIDS-Related and Non- AIDS-Related Mortality: A Temporal Analysis from Time of Seroconversion (SC)

Objectives: To estimate changes of AIDS and non-AIDS mortalities from 1996 to 2010 comparing (2004-2010) vs. (1996-2003) periods from the time of HIV-seroconversion (SC). Methods: Data derived from an Italian multicentre prospective and open cohort; competing risks approach was applied estimating the cumulative incidence functions (CIF) for AIDS and non-AIDS deaths over time from SC with delayed entries in the two cART periods. Cox-cause-specific hazards models were applied to estimate relative hazards (RH) of AIDS and non-AIDS related deaths. Results: Of 2,249 individuals with known SC date followed from SC and from January 1996 to December 2010, 1,779 were survived, seroconverted or followed during 1996-2003, while 1,715 during 2004-2010. A total of 278 deaths occurred from 1996 to 2010: 197 in the early years of cART [61 (31%) non-AIDS deaths], and 81 during more recent cART period [48 (59%) non-AIDS deaths]. The CIF of AIDS related deaths was higher than CIF of non-AIDS related deaths in the early period [for instance, estimates at 15 yrs from SC: CIF of AIDS-related death = 0.15 (95% CI: 0.12-0.19 ) and CIF of non-AIDS related = 0.09 (95% CI: 0.07-0.12)], whilst in 2004-2010 period the CIF of non-AIDS related deaths was slightly higher [estimates at 15 yrs from SC: CIF of non-AIDS related = 0.03 (95% CI: 0.02-0.04) vs. CIF of AIDS-related death = 0.02 (95% CI: 0.02-0.04)]. Comparing the two periods by Cox proportional-cause-specific models, the hazard was lower for AIDS deaths than for non-AIDS related deaths [RH of non-AIDS deaths from last viral load (VL) < 200 copies/mL was 0.60 (95% CI (0.35-1.03)], while of AIDS-deaths was 0.32 (95% CI: 0.17-0.62), both RH relative to (2004-2010) vs. (1996- 2003)]. Conclusions: Considering early years of the cART period as a reference, we observed a decrease in both AIDS and non-AIDS-mortalities. In more recent cART years, non-AIDS mortality tended to decline less than AIDS-relatedmortality since HIV-SC, even after effective cART.