Julia del Amo

Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis

In a systematic review and meta-analysis, Amitabh Suthar and colleagues investigate the association between antiretroviral therapy and the reduction in the incidence of tuberculosis in adults with HIV infection.

When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study.

BACKGROUND Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. OBJECTIVE To identify the optimal CD4 cell count at which cART should be initiated. DESIGN Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L. SETTING HIV clinics in Europe and the Veterans Health Administration system in the United States. PATIENTS 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis. MEASUREMENTS Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. RESULTS Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. LIMITATIONS CD4 cell count at cART initiation was not randomized. Residual confounding may exist. CONCLUSION Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.

Response to combination antiretroviral therapy: variation by age.

Objective:To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. Design and setting:Multicohort collaboration of 33 European cohorts. Subjects:Forty-nine thousand nine hundred and twenty-one antiretroviral-naive individuals starting combination antiretroviral therapy from 1998 to 2006. Outcome measures:Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/μl (immunological response) and new AIDS/death were analysed using survival methods. Ten age strata were chosen: less than 2, 2–5, 6–12, 13–17, 18–29, 30–39 (reference group), 40–49, 50–54, 55–59 and 60 years or older; those aged 6 years or more were included in multivariable analyses. Results:The four youngest age groups had 223, 184, 219 and 201 individuals and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2–54.1%) and 59.2% (58.7–59.6%) had experienced a virological and immunological response. The probability of virological response was lower in those aged 6–12 (adjusted hazard ratio: 0.87) and 13–17 (0.78) years, but was higher in those aged 50–54 (1.24), 55–59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults and reduced in those 60 years or older. Those aged 55–59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. Conclusion:Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy CD4 cell counts, may place this group at increased clinical risk. The poorer virological responses in children may increase the likelihood of emergence of resistance.

The hepatitis C epidemic among HIV-positive MSM: incidence estimates from 1990 to 2007

Background:Outbreaks of acute hepatitis C virus (HCV) infection among HIV-infected MSM have been described since 2000. However, phylogenetic analysis suggests that the spread of HCV started around 1996. We estimated the incidence of HCV in HIV-infected MSM with well estimated dates of HIV seroconversion from 1990 to 2007. Methods:Data from 12 cohorts within the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) Collaboration were used. HCV incidence was estimated using standard incidence methods and methods for interval-censored data. We accounted for the fact that routine HCV data collection in each cohort started in different calendar years. Results:Of 4724 MSM, 3014 had an HCV test result and were included. Of these, 124 (4%) had only positive HCV test results, 2798 (93%) had only negative results and 92 (3%) had both. In 1990, HCV incidence ranged from 0.9 to 2.2 per 1000 person-years, depending on the analysis strategy used. HCV incidence increased up to 1995 when it was estimated to range between 5.5 and 8.1 per 1000 person-years. From 2002 onwards, it increased substantially to values between 16.8 and 30.0 per 1000 person-years in 2005 and between 23.4 and 51.1 per 1000 person-years in 2007. Conclusion:Our data support phylodynamic findings that HCV incidence had already increased among HIV-infected MSM from the mid-1990s. However, the main expansion of the HCV epidemic started after 2002. Incidence estimates obtained from cohort studies may help identify changes in the spread of important infections earlier and should guide routine testing policies to minimize further disease burden.

Time From Human Immunodeficiency Virus Seroconversion to Reaching CD4+ Cell Count Thresholds <200, <350, and <500 Cells/mm3: Assessment of Need Following Changes in Treatment Guidelines

BACKGROUND Recent updates of human immunodeficiency virus (HIV) treatment guidelines have raised the CD4+ cell count thresholds for antiretroviral therapy initiation from 350 to 500 cells/mm(3) in the United States and from 200 to 350 cells/mm³ in mid- and low-income countries. Robust data of time from HIV seroconversion to CD4+ cell counts of 200, 350, and 500 cells/mm³ are lacking but are needed to inform health care planners of the likely impact and cost effectiveness of these and possible future changes in CD4+ cell count initiation threshold. METHODS Using Concerted Action on Seroconversion to AIDS and Death in Europe data from individuals with well-estimated dates of HIV seroconversion, we fitted mixed models on the square root of CD4+ cell counts measured before combined antiretroviral therapy (cART) initiation. Restricting analyses to adults (age >16 years), we predicted time between seroconversion and CD4+ cell count <200, <350, and <500 cells/mm³ as well as CD4+ cell count distribution and proportions reaching these thresholds at 1, 2, and 5 years after seroconversion. RESULTS Median (interquartile range [IQR]) follow-up for the 18495 eligible individuals from seroconversion while cART-free was 3.7 years (1.5, 7). Most of the subjects were male (78%), had a median age at seroconversion of 30 years (IQR, 25-37 years), and were infected through sex between men (55%). Estimated median times (95% confidence interval [CI]) from seroconversion to CD4+ cell count <500, <350, and <200 cells/mm(3) were 1.19 (95% CI, 1.12-1.26), 4.19 (95% CI, 4.09-4.28), and 7.93 (95% CI, 7.76-8.09) years, respectively. Almost half of infected individuals would require treatment within 1 year of seroconversion for guidelines recommending its initiation at 500 cells/mm³, compared with 26% and 9% for guidelines recommending initiation at 350 and 200 cells/mm³, respectively. CONCLUSIONS These data suggest substantial increases in the number of individuals who require treatment and call for early HIV testing.

Effectiveness of highly active antiretroviral therapy in spanish cohorts of HIV seroconverters: differences by transmission category

Objective: To evaluate the population effectiveness of highly active antiretroviral therapy (HAART) in HIV progression and determine the heterogeneity of the effect of HAART in GEMES (Spanish multicenter study of seroconverters). Design: Multicenter cohort study. Methods: Data from 1091 persons with well-documented HIV seroconversion dates from 1980s to January 2000 were analysed. Risk of AIDS and death in subjects with same duration of HIV infection were compared in different calendar periods; before 1992, 1992–1995 (reference), 1996–1997, 1998 and 1999 with Kaplan–Meier methods and Cox proportional hazards models, allowing for late entry, fitting calendar period as time-dependent covariate and adjusting for transmission category, age and gender. Results: Statistically significant reductions in the risk of AIDS were first observed in 1998 [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.35–1.01] becoming more pronounced in 1999 (HR, 0.45; 95% CI, 0.24–0.84). Reduction in the risk of death was seen in 1997, though only reached borderline significance in 1999 (HR, 0.53; 95% CI, 0.26–1.07). Progression to AIDS and death was slower in women (HR, 0.68; 95% CI, 0.46–0.99 and HR, 0.53; 95% CI, 0.33–0.87, respectively). Compared with men who have sex with men (MSM), intravenous drug users (IDU) had lower reductions in the risk of AIDS and death. Conclusions: Reductions in incidence of AIDS and death in GEMES are seen after 1998 and 1999, respectively, compared with 1992–1995, being more pronounced in MSM compared with IDU, the commonest category in Spain.

The contribution of a gender perspective to the understanding of migrants’ health

In 2005 women represented approximately half of all 190 million international migrants worldwide. This paper addresses the need to integrate a gender perspective into epidemiological studies on migration and health, outlines conceptual gaps and discusses some methodological problems. We mainly consider the international voluntary migrant. Women may emigrate as wives or as workers in a labour market in which they face double segregation, both as migrants and as women. We highlight migrant women’s heightened vulnerability to situations of violence, as well as important gaps in our knowledge of the possible differential health effects of factors such as poverty, unemployment, social networks and support, discrimination, health behaviours and use of services. We provide an overview of the problems of characterising migrant populations in the health information systems, and of possible biases in the health effects caused by failure to take the triple dimension of gender, social class and ethnicity into account.

HIV testing and counselling for migrant populations living in high-income countries: a systematic review.

Background: The barriers to HIV testing and counselling that migrants encounter can jeopardize proactive HIV testing that relies on the fact that HIV testing must be linked to care. We analyse available evidence on HIV testing and counselling strategies targeting migrants and ethnic minorities in high-income countries. Methods: Systematic literature review of the five main databases of articles in English from Europe, North America and Australia between 2005 and 2009. Results: Of 1034 abstracts, 37 articles were selected. Migrants, mainly from HIV-endemic countries, are at risk of HIV infection and its consequences. The HIV prevalence among migrants is higher than the general population’s, and migrants have higher frequency of delayed HIV diagnosis. For migrants from countries with low HIV prevalence and for ethnic minorities, socio-economic vulnerability puts them at risk of acquiring HIV. Migrants have specific legal and administrative impediments to accessing HIV testing—in some countries, undocumented migrants are not entitled to health care—as well as cultural and linguistic barriers, racism and xenophobia. Migrants and ethnic minorities fear stigma from their communities, yet community acceptance is key for well-being. Conclusions: Migrants and ethnic minorities should be offered HIV testing, but the barriers highlighted in this review may deter programs from achieving the final goal, which is linking migrants and ethnic minorities to HIV clinical care under the public health perspective.

Delayed diagnosis of HIV infection in a multicenter cohort: prevalence, risk factors, response to HAART and impact on mortality.

To study the prevalence of Delayed HIV Diagnosis (DHD) and its associated risk factors, to evaluate the effect of DHD on virological and immunological responses to HAART and to estimate the impact of DHD on all-causes mortality. Prospective cohort of 2, 564 HIV-positive HAART-naïve subjects attending 19 hospitals in Spain, 2004-2006. Estimations were made by logistic regression and survival analyses by Cox regression models. Prevalence of DHD was 37.3% (35.0-39.6). DHD was related to low educational level (OR:1.31, 95% CI:1.0-1.7). Compared to men who have sex with men (MSM), DHD was more frequent in heterosexuals (OR:1.9 95% CI:1.5-2.5) and injection drug users (IDUs) (OR:2.0 95% CI:1.5-2.8). An interaction between age and sex was found. Although risk of having DHD did not increase after age 30 in women, it increased linearly with age in men. No differences in virological (OR 1.2 95% CI: 0.8-1.8) and CD4 T cell (OR 1.1 95% CI: 0.7-1.8) responses to HAART were seen. The adjusted hazard ratio for death in patients with DHD was 5.2, (95% CI: 1.9-14.5). DHD is very common, especially in older men, heterosexuals and IDUs. Although we did not find differences in virological and immunological responses to HAART, we did observe higher mortality in people with DHD. Increased efforts to early diagnose HIV infection are urgently needed.

Gender Differences in HIV Progression to AIDS and Death in Industrialized Countries: Slower Disease Progression Following HIV Seroconversion in Women

To evaluate sex differences in human immunodeficiency virus (HIV) disease progression before (pre-1997) and after (1997-2006) introduction of highly active antiretroviral therapy, the authors used data from a collaboration of 23 HIV seroconverter cohort studies from Europe, Australia, and Canada restricted to the 6,923 seroconverters infected through injecting drug use and sex between men and women. Within a competing risk framework, they used Cox proportional hazards models allowing for late entry to evaluate sex differences in time from HIV seroconversion to death, to acquired immunodeficiency syndrome (AIDS), and to each first AIDS-defining disease and death without AIDS. While no significant sex differences were found before 1997, from 1997 onward, women had a lower risk of AIDS (adjusted cumulative relative risk (aCRR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and death (adjusted hazard ratio = 0.68, 95% CI: 0.56, 0.82) than men did. Compared with men, women also had lower risks of AIDS dementia complex (aCRR = 0.23, 95% CI: 0.07, 0.74), tuberculosis (aCRR = 0.60, 95% CI: 0.39, 0.92), Kaposis sarcoma (aCRR = 0.27, 95% CI: 0.07, 0.99), lymphomas (aCRR = 0.47, 95% CI: 0.23, 0.96), and death without AIDS (aCRR = 0.74, 95% CI: 0.56, 0.98). Sex differences in HIV disease progression have become larger and statistically significant in the era of highly active antiretroviral therapy, supporting a stronger impact of health interventions among women.