Highly Active Antiretroviral Therapy Period Research Articles

The increasing prevalence of HIV/Helicobacter pylori co-infection over time, along with the evolution of antiretroviral therapy (ART).

Helicobacter pylori (H. pylori) is one of the most common human bacterial infections with prevalence rates between 10–80% depending upon geographical location, age and socioeconomic status. H. pylori is commonly found in patients complaining of dyspepsia and is a common cause of gastritis. During the course of their infection, people living with HIV (PLHIV) often have a variety of gastrointestinal symptoms including dyspepsia and while previous studies have reported HIV and H. pylori co-infection, there has been little data clarifying the factors influencing this. The aim of this case-control study was to document the prevalence of H. pylori co-infection within the HIV community as well as to describe endoscopic findings, gastritis topography and histology, along with patient demographic characteristics across three different periods of time during which antiretroviral therapy (ART) has evolved, from pre- highly active antiretroviral therapy (HAART) to early and modern HAART eras. These data were compared to well-matched HIV negative controls. Two hundred and twelve PLHIV were compared with 1,617 controls who underwent their first esophagogastroduodenoscopy (EGD) to investigate dyspepsia. The prevalence of H. pylori co-infection among PLHIV was significantly higher in the early (30.2%) and modern HAART period (34.4%) compared with those with coinfection from the pre-HAART period (18.2%). The higher rates seen in patients from the HAART eras were similar to those observed among HIV negative controls (38.5%). This prevalence increase among co-infected patients was in contrast to the fall in prevalence observed among controls, from 60.7% in the early period to 52.9% in the second observed period. The three PLHIV co-infected subgroups differed regarding gastritis topography, morphology and pathology. This study suggests that ART has an important impact on the endoscopic and histological features of gastritis among HIV/H. pylori co-infected individuals, raising the possibility that H. pylori-induced gastritis could be an immune restoration disease.

Neurological complications of HIV infection in pre-HAART and HAART era: a retrospective study.

The introduction of highly active anti-retroviral therapy (HAART) led to a radical change in the natural history of HIV infection and of the associated neurological opportunistic infections. However, the mortality of central nervous system (CNS) complications and opportunistic infections is still high in untreated HIV-infected individuals or in patients unaware of their HIV infection. We describe the outcome of HIV-infected patients followed at a single center for AIDS-related neurological syndromes in the 16 years following the introduction of HAART, and compare the findings with those in patients admitted up to 1996. We have conducted a retrospective study of patients with HIV infection or AIDS (based on WHO criteria and classified according to the 1993 CDC criteria) admitted during 20 years (January 1992 to March 2012) to the Infectious Diseases Unit of the University of Verona for the presence of focal or widespread CNS lesion on neuroimaging. Clinical history, CD4 cell count, HIV-RNA level, neurological examination, imaging, cerebrospinal fluid examination and eventual cerebral biopsy results were reviewed as well as the final neurological diagnosis and the treatment. The survival time from the clinical onset of the neurologic syndrome to death was calculated for each patient who died. A statistical analysis was performed comparing data collected up to and after 1996, i.e., before and after HAART introduction. Among 1043 patients with HIV infection or AIDS admitted to the Infectious Diseases Unit of the University of Verona between January 1992 and March 2012, 114 had a CNS lesion. The following diseases were observed: neurotoxoplasmosis (NT), progressive multifocal leukoencephalopathy), primary central nervous system lymphoma (PCNSL), the severe form of HIV-associated neurocognitive disorder, cryptococcal encephalitis (CE) and lesions of undetermined origin. The follow-up period was 4 weeks to 72 months both in the pre-HAART and HAART era. Cerebral lesions were detected in 53/243 patients (21.8%) in the pre-HAART era and in 61/801 patients (7.6%) in the HAART era (p < 0.001). Most patients who developed a neurological complication in the HAART period (40/59, 67.8%) were untreated or did not know to be HIV-infected; in particular, 27.9% of patients with a CNS lesion in the HAART era were unaware of their HIV infection vs 13.2% in the pre-HAART era (p < 0.05). Some patients were not virologically suppressed (14/59, 23.7%) or were immunological non-responders (undetectable viral load, with CD4 count <200 cells/μL; 4/59, 6.8%). Other statistically significant data were the mean age at the onset of neurological complications (32.6 ± 5.4 years in the pre-HAART, 40.3 ± 9.5 in the HAART group, p < 0.001) and the mean CD4 cell count at the onset of illness (median of 38 cells/µL (2-215) in the pre-HAART, 77 cells/µL (2-752) in the HAART group; p < 0.001). In the HAART era a reduction of PCNSL and NT was observed. Our results, while confirming a decrease in the incidence of opportunistic infections of the CNS in the HAART era, show that late presentation of patients with HIV infection remains an important issue in our catchment area.

Elevated NT-pro-brain natriuretic peptide level is independently associated with all-cause mortality in HIV-infected women in the early and recent HAART eras in the Women's Interagency HIV Study cohort.

BackgroundHIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminal-pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women.DesignProspective cohort study.Methods and ResultsWe measured NT-proBNP in 936 HIV-infected and 387 age-matched HIV-uninfected women early (10/11/94 to 7/17/97) and 1082 HIV-infected and 448 HIV-uninfected women late (4/1/08 to 10/7/08) in the highly active antiretroviral therapy (HAART) periods in the Women’s Interagency HIV Study. An NT-proBNP >75th percentile was more likely in HIV-infected persons, but only statistically significant in the late period (27% vs. 21%, unadjusted p = 0.03). In HIV-infected participants, NT-proBNP>75th percentile was independently associated with worse 5-year survival in the early HAART period (HR 1.8, 95% CI 1.3–2.4, p<0.001) and remained a predictor of mortality in the late HAART period (HR 2.8, 95% CI 1.4–5.5, p = 0.002) independent of other established risk covariates (age, race/ethnicity, body mass index, smoking, hepatitis C serostatus, hypertension, renal function, and hemoglobin). NT-proBNP level was not associated with mortality in HIV-uninfected women.ConclusionNT-proBNP is a novel independent marker of mortality in HIV-infected women both when HAART was first introduced and currently. As NT-proBNP is often associated with both pulmonary hypertension and left ventricular dysfunction, these findings suggest that these conditions may contribute significantly to adverse outcomes in this population, requiring further definition of causes and treatments of elevated NT-proBNP in HIV-infected women.

Trends and Predictors of Non–AIDS-Defining Cancers in Men and Women With HIV Infection

The incidence of non-AIDS-defining cancers (NADCs) in HIV-positive patients has increased over recent years. Most studies of the risk and spectrum of NADCs are primarily based on male populations, and only a few have provided specific information regarding females. We retrospectively analyzed all incident NADCs occurring in a cohort of HIV-positive patients followed up between 1985 and 2011. Incidence rates before and after the introduction of highly active antiretroviral therapy (HAART) were examined using Poisson regression models. Standardized incidence ratios (SIRs) were used to compare the cancer risk of HIV-infected subjects with that of the age- and gender-matched general population as estimated by the Milan Cancer Registry. Five thousand nine hundred twenty-four patients (4382 men and 1542 women) contributed 50,990 person-years to the follow-up. Among them, 144 had new NADC diagnosis. The overall incidence increased from 1.0 case/1000 person-years in the pre-HAART period to 4.5 cases/1000 person-years in the HAART period (P < 0.01). In women, the risks were higher than expected in the case of cancer of the vulva (SIR = 69.2), Hodgkin lymphoma (SIR = 7.5), anal cancer (SIR = 41.2), and lung cancer (SIR = 4.8). In men, the risks were higher than expected in the case of anal cancer (SIR = 91.5), Hodgkin lymphoma (SIR = 13.0), tonsil cancer (SIR = 10.9), lung cancer (SIR = 2.1), and liver cancer (SIR = 7.1). The spectrum and incidence of NADCs in our cohort increased over time. The incidence of NADCs, especially virus- and smoking-associated cancers, was significantly higher than expected in HIV-positive men and women.

Neurological opportunistic infections and neurological immune reconstitution syndrome: impact of one decade of highly active antiretroviral treatment in a tertiary hospital

Despite the reported decrease in the incidence and mortality rates of central nervous system (CNS) infections after the introduction of highly active antiretroviral therapy (HAART), few studies have focused on the global incidence and the relationship of these diseases with immune reconstitution inflammatory syndrome (IRIS) in the developed world. A descriptive cohort study of all consecutive adult HIV-infected patients with CNS opportunistic infections diagnosed between 2000 and 2010 in a tertiary hospital in Spain was carried out. Demographic, clinical, laboratory, and microbiological data were recorded. Patients were followed up until death or loss to follow-up or until 30 July 2011, when the study finished. The significance of differences in the incidence rate between early and late HAART periods was determined using the Mantel-Haenszel test. Survival distribution was estimated using the Kaplan-Meier method. A total of 110 cases of CNS infections were diagnosed. The incidence of CNS opportunistic infections decreased from 9 cases per 1000 HIV-infected patients per year in the early HAART period to 3.8 in the late HAART period (P = 0.04). Overall, the estimated mean survival time was 58.8 months (95% confidence interval 47.1-70.6 months). Of the 110 patients, 18 (16.4%) met the criteria of IRIS, 10 (55.6%) were paradoxical and eight (44.4%) were unmasking. IRIS was not associated with a higher mortality rate. The annual incidence of CNS infections decreased progressively during the period of study. The mortality rate associated with these diseases remains high despite HAART. The development of IRIS associated with neurological infections had no influence on prognosis.

Epidemiological Patterns of AIDS in a Reference Center from Catanduva, S&amp;#227;o Paulo State, Brazil

Objective: Hereby we present the epidemiological and clinical profile of HIV-infected population before and during the highly active antiretroviral therapy (HAART) era from a tertiary care hospital in the Southeastern region of Brazil. Methods: A retrospective, cross-sectional and descriptive study was carried out, this involved the analysis of the medi-cal records of patients diagnosed with HIV-1/AIDS admitted to Hospital Escola Emilio Carlos, located in the munici-pality of Catanduva, State of S?o Paulo, Brazil. Results: In both pre-HAART and HAART periods, HIV-1 infection was more prevalent in men. Heterosexuality and secondary education were associated with AIDS in the HAART period. Statistically significant association was only observed for co-infection with HIV-1/Hepatitis C in the pre-HAART era and the number of patients with opportunistic infection (OI) was lower in the HAART period. Among all OI it is worth mentioning pulmonary pneumocystosis, which despite being common in two periods, its occurrence was considerably greater in the pre-HAART era. Concerning the distribution of OIs according to the HIV-1 viral load and serial count of T CD4+ lymphocytes, a significant association was observed. The association between the number of deaths by OIs and death in the 1st year of diagnosis in the HAART treatment was significant. Conclusions: The clinical and epidemiological profile of a specialized HIV-1/AIDS center in Catanduva, Southeastern Brazilian region, is consistent with the epidemiology of AIDS in the country.

The Impact of Kidney Function at Highly Active Antiretroviral Therapy Initiation on Mortality in HIV-Infected Women

In the early highly active antiretroviral therapy (HAART) era, kidney dysfunction was strongly associated with death among HIV-infected individuals. We re-examined this association in the later HAART period to determine whether chronic kidney disease remains a predictor of death after HAART initiation. To evaluate the effect of kidney function at the time of HAART initiation on time to all-cause mortality, we evaluated 1415 HIV-infected women initiating HAART in the Women's Interagency HIV Study. Multivariable proportional hazards models with survival times calculated from HAART initiation to death were constructed; participants were censored at the time of the last available visit or December 31, 2006. Chronic kidney disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m) at HAART initiation was associated with higher mortality risk adjusting for age, race, hepatitis C serostatus, AIDS history, and CD4 cell count (hazard ratio 2.23, 95% confidence interval: 1.45-3.43). Adjustment for hypertension and diabetes history attenuated this association (hazard ratio = 1.89, confidence interval: 0.94-3.80). Lower kidney function at HAART initiation was weakly associated with increased mortality risk in women with prior AIDS (hazard ratio = 1.09, confidence interval: 1.00-1.19, per 20% decrease in estimated glomerular filtration rate). Kidney function at HAART initiation remains an independent predictor of death in HIV-infected individuals, especially in those with a history of AIDS. Our study emphasizes the necessity of monitoring kidney function in this population. Additional studies are needed to determine mechanisms underlying the increased mortality risk associated with chronic kidney disease in HIV-infected persons.

One year survival of HIV-infected veterans with CD4 < 100 cells/mm3: data from a veteran cohort

Survival among HIV-infected patients markedly improved with the introduction of highly active antiretroviral therapy (HAART). Easier to take and more effective HAART options have improved the one-year virologic success rate among naïve patients. Numerous studies have shown that initiating HAART and restoration of CD4 cells positively impact survival. There are only a few evaluations that have been carried out on the changes in survival among patients who are severely immunosuppressed. We evaluated survival among a cohort of veterans with CD4<100 cells/mm3 (CD4 < 100) in three time periods reflecting early, mid, and recent HAART. Using the HIV clinic database, all patients with CD4 < 100 seen between 1996 and 2004 were identified (n=394). Patients entered Cohorts 1 (n=219), 2 (n=72), and 3 (n=103) in 1996–1998, 1999–2001, and 2002–2004, respectively. Data on demographics, AIDS-defining illnesses, co-morbidities, treatment, CD4, and viral load (VL) were abstracted. Survival analysis controlling for the above variables was performed and odds ratios with 95% confidence intervals were calculated. Rate of virologic suppression was higher for Cohort 2 when compared to Cohort 1 (63% vs. 46%, p<0.05), but lower for Cohort 3 when compared to Cohort 2 (49%, p<0.05). Survival at one year was high for Cohorts 1 and 2 (92–95%), but significantly lower in Cohort 3 (80%). On logistic regression analysis and for the whole cohort, HAART use, achieving a CD4 > 200 and VL<400 were independent predictors of survival. Older age at cohort entry and having a diagnosis of lymphoma, Mycobacterium avium complex infection, coronary artery disease, or renal insufficiency were negative predictors. In the most recent HAART period 2002–2004, one year survival after CD4 < 100 significantly decreased in spite of availability of specialized HIV clinical and support services and antiretrovirals. Our results suggest that more than better drugs are needed for improving survival among certain patient populations with advanced immunosuppression.

Herpes Zoster Among HIV-Infected Patients in the Highly Active Antiretroviral Therapy Era: Korean HIV Cohort Study

Herpes Zoster Among HIV-Infected Patients in the Highly Active Antiretroviral Therapy Era: Korean HIV Cohort Study

Continuing declines in some but not all HIV-associated cancers in Australia after widespread use of antiretroviral therapy

To describe changes in cancer incidence in people with HIV in Australia since the introduction of highly active antiretroviral therapy (HAART). Population-based, retrospective cohort study of people with HIV (n = 20 232) using data linkage between national registers of HIV/AIDS and cancer in 1982-2004. Age-adjusted and sex-adjusted incidence rate ratios with 95% confidence intervals were calculated to compare site-specific cancer incidence during the early (1996-1999) and late (2000-2004) HAART periods with that prior to HAART (1982-1995). Five-year age-specific, sex-specific, calendar year-specific, and state-specific standardized incidence ratios with 95% confidence interval were also calculated for each period. Incidence of Kaposi sarcoma and non-Hodgkin lymphoma declined significantly (Ptrend < 0.001). Incidence of Hodgkin lymphoma was significantly higher during the early-HAART period (incidence rate ratio 2.34, 95% confidence interval 1.19-4.63) but declined thereafter (Pdiff = 0.014). Incidence of anal cancer was unchanged (Ptrend = 0.451) and remained raised more than 30-fold. Incidence declined significantly for melanoma (Ptrend = 0.041) and prostate cancer (Ptrend = 0.026), and, during the late-HAART period, was lower than in the general population for both cancers. Incidence of colorectal cancer was consistently lower than in the general population. Incidence of Kaposi sarcoma and non-Hodgkin lymphoma has continued to decline among people with HIV in Australia, though it remains very substantially elevated. Incidence of Hodgkin lymphoma may now also be declining. Incidence of anal cancer has remained stable, and it is now the third most common cancer in HIV-infected Australians. Reasons for the reduced incidence of colorectal and prostate cancer, and more recently of melanoma, are unclear.

Hypoadiponectinemia in lipodystrophic HIV individuals: A metabolic marker of subclinical cardiac damage

Background and aim To evaluate cardiovascular abnormalities in highly active antiretroviral therapy (HAART) treated HIV patients with no signs or symptoms of cardiovascular impairment, and to assess the relative role of multiple concomitant risk factors. Methods and results Forty-four consecutive HIV subjects (mean age 41 ± 6 yrs) were enrolled. Inclusion criteria were HIV infection, CD4 + cell count > 150/ml, HAART treatment for at least 4 years. Metabolic serum levels, morphological and functional echocardiographic parameters were assessed in all subjects. Sixteen healthy age and sex matched subjects with no cardiovascular risk factors were recruited as controls. HIV patients showed increased left ventricular mass index with reduced mid-wall fractional shortening (mFS) when compared to controls (50.2 ± 10.5 vs. 38.6 ± 14.4, p = 0.05 and 18.3 ± 0.6 vs. 21.9 ± 0.7, p < 0.05, respectively). Twenty-nine patients were lipodystrophic (LD) and showed a longer HAART period ( p = 0.0004) and greater use of protease inhibitors (PI) ( p = 0.001). Coronary flow reserve (CFR) was significantly reduced in HIV patients as compared to controls ( p < 0.0001), as it was in LD subjects when compared to non-lipodystrophic ones (NLD) ( p < 0.001). Adiponectin concentrations were found to be significantly lower in LD subjects than in NLD ones (7.8 ± 0.8 vs. 13.8 ± 1.2 μg/ml, p = 0.01), and showed a direct correlation with CFR. In multiple regression analysis, insulin, HDL and adiponectin accounted for 63% of CFR variations. Conclusions Left ventricular hypertrophy, depressed mFS and reduced CFR represent the main signs of subclinical cardiac damage in HIV subjects treated with HAART. Hypoadiponectinemia in these subjects seems to be a metabolic risk factor of cardiovascular impairment.

Highly Active Antiretroviral Therapy and the Incidence of Non–AIDS-Defining Cancers in People With HIV Infection

The effect of highly active antiretroviral therapy (HAART) on the incidence of non-AIDS-defining cancers (NADCs) is unclear. We have investigated the occurrence of NADCs in a prospective cohort of 11,112 HIV-positive individuals, with 71,687 patient-years of follow-up. Standardized incidence ratios (SIRs) were calculated using general population incidence data. We investigated the effect of calendar period, HIV parameters, and immunologic and treatment-related factors on the incidence of these cancers using univariate and multivariate analyses. The SIR for all NADCs was 1.96 (95% CI, 1.66 to 2.29). There was no significant excess in incidence in the pre-HAART era (1983 to 1995; SIR, 0.95; 95% CI, 0.58 to 1.47). However, the incidence increased in the early HAART period (1996 to 2001) and remains elevated in the most recent established HAART period (2002 to 2007; SIR, 2.05; 95% CI, 1.51 to 2.72, and SIR 2.49; 95% CI, 2.00 to 3.07, respectively). Multivariate analysis showed that use of HAART (hazard ratio [HR] = 1.64; 95% CI, 1.13 to 2.39) and a nadir CD4 count less than 200/microL (HR = 1.67; 95% CI, 1.10 to 2.54) were associated with an increased risk. Only the non-nucleoside reverse transcriptase inhibitors (NNRTIs) were associated with a significantly increased risk of NADCs (HR = 1.45; 95% CI, 1.01 to 2.08). Much of this association was attributable to an increased risk of Hodgkin's lymphoma with NNRTIs (HR = 2.20; 95% CI, 1.03 to 4.69). Since the introduction of HAART, there has been a significantly increased risk of NADCs, which has now stabilized. A number of factors are associated with this increased risk, including HAART use. There may be an association between the use of NNRTIs and the development of Hodgkin's lymphoma.

Trends of mortality and causes of death among HIV‐infected patients in Taiwan, 1984–2005

The aim of this study was to analyse the trends of mortality and causes of death among HIV-infected patients in Taiwan from 1984 to 2005. Registered data and death certificates for HIV-infected patients from Taiwan Centers for Disease Control were reviewed. Mortality rate and causes of deaths were compared among patients whose HIV diagnosis was made in three different study periods: before the introduction of highly active antiretroviral therapy (HAART) (pre-HAART: from 1 January 1984 to 31 March 1997), in the early HAART period (from 1 April 1997 to 31 December 2001), and in the late HAART period (from 1 January 2002 to 31 December 2005). A subgroup of 1161 HIV-infected patients (11.4%) followed at a university hospital were analysed to investigate the trends of and risk factors for mortality. For 10 162 HIV-infected patients with a mean follow-up of 1.97 years, the mortality rate of HIV-infected patients declined from 10.2 deaths per 100 person-years (PY) in the pre-HAART period to 6.5 deaths and 3.7 deaths per 100 PY in the early and late HAART periods, respectively (P<0.0001). For the 1161 patients followed at a university hospital (66.8% with CD4 count <200 cells/microL), HAART reduced mortality by 89% in multivariate analysis, and the adjusted hazard ratio for death was 0.28 (95% confidence interval 0.24, 0.33) in patients enrolled in the late HAART period compared with those in the pre-HAART period. Seventy-six per cent of the deaths in the pre-HAART period were attributable to AIDS-defining conditions, compared with 36% in the late HAART period (P<0.0001). The leading causes of non-AIDS-related deaths were sepsis (14.7%) and accidental death (8.3%), both of which increased significantly throughout the three study periods. Compared with patients acquiring HIV infection through sexual contact, injecting drug users were more likely to die from non-AIDS-related causes. The mortality of HIV-infected patients declined significantly after the introduction of HAART in Taiwan. In the HAART era, AIDS-related deaths decreased significantly while deaths from non-AIDS-related conditions increased.

Pneumocystis jiroveci Pneumonia in Patients With AIDS in the Inner City: A Persistent and Deadly Opportunistic Infection

Highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality of opportunistic infections including Pneumocystis jiroveci pneumonia (PCP) among HIV-infected individuals. We performed a hospital-based retrospective cohort study among a population of medically underserved inner city persons living in Atlanta, Georgia, diagnosed with confirmed PCP to compare the epidemiology and outcomes of PCP during 2 defined periods: 1990 to 1995, or pre-HAART period, and 1996 to 2001, or HAART period. A total of 488 patients were available for analysis. The overall mortality rate was 47% during the pre-HAART era compared with 37% during the HAART era (P = 0.02). However, among those patients that required medical intensive care unit admission and mechanical ventilation, the mortality rate was particularly high, with over 80% of patients dying as a result of their episode of PCP during both periods. PCP was the initial presentation of HIV infection in 39.3% in the pre-HAART period with a mortality rate of 52%, in contrast with 37% in the HAART period, with a mortality rate of 45%, respectively (P = NS). Only 30.7% in the pre-HAART period and 31.1% of patients in the HAART period were receiving PCP prophylaxis. The overall risk of death, when we combined both groups in the analysis, was higher for those patients who did not take PCP prophylaxis, those who smoked tobacco, and those who were admitted to the medical intensive care unit and required mechanical ventilatory support. Our findings suggest that despite the availability of HAART, PCP continues to cause a significant burden of disease among inner-city HIV-infected populations.

Pneumococcal pneumonia in HIV-infected patients by antiretroviral therapy periods

To ascertain the relationship between periods of various antiretroviral therapies and the incidence of first community-acquired pneumococcal pneumonia (CAPP) among HIV-1 infected patients. We analysed 4075 patients enrolled prospectively in the Lyon section of the French Hospital Database on HIV between 1993 and 2004, stratified into three groups. The first group (G1) included patients for whom enrolment and last follow-up were before the highly active antiretroviral therapy (HAART) period (beginning 1 July 1996); the second group (G2) comprised patients who were enrolled before HAART but had last follow-up in the HAART period; the third group (G3) included patients for whom both enrolment and last follow-up took place in the HAART period. Fifty-five CAPP episodes were identified. The incidence of CAPP per 1000 patient-years declined over time, from 10.6 to 1.5 and 2.5 in calendar periods G1, G2 and G3, respectively (P=0.004 for linear trend). Factors associated with a decreased risk of CAPP were lower age, baseline CD4 count >or=200 cells/microL and more recent years of enrolment, when HAART use became extensive (P<0.001). The use of intravenous drugs increased the risk of CAPP (P<0.001). There has been a significant reduction in the incidence of CAPP in HIV-1 infected patients since the advent of HAART.

Determinants of HIV Progression and Assessment of the Optimal Time to Initiate Highly Active Antiretroviral Therapy

We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.

The Independent Effect of Highly Active Antiretroviral Therapy on Severe Opportunistic Disease Incidence and Mortality in HIV-Infected Adults in Côte D'Ivoire

Studies in developed countries have shown highly active antiretroviral therapy (HAART) decreases incidence of severe opportunistic diseases (ODs) in HIV-infected patients beyond that which is expected from changes in CD4+ T-cell count. To estimate the independent impact of HAART on reducing ODs and mortality in Côte d'Ivoire. Within two longitudinal studies of HIV-infected adults (1996-2003), we identified time on 'cotrimoxazole alone' and 'HAART plus cotrimoxazole' WHO stage 3-4 defining events and severe malaria were divided into those preventable and not preventable with cotrimoxazole. Incidence of ODs by CD4 count stratum was estimated using incidence density analysis. CD4+ T-cell count at time of OD was estimated using linear interpolation. Using Poisson regression, we estimated the effect of HAART on OD incidence and mortality by CD4 count stratum. Totals of 446 and 135 adults were followed during 6,216 and 3,412 person-months in the cotrimoxazole alone and HAART plus cotrimoxazole periods, respectively. There was a CD4+ T-cell-independent risk reduction for ODs and mortality during the HAART plus cotrimoxazole period compared with cotrimoxazole alone, which varied by time on HAART, CD4 count stratum and OD type. It was mainly seen after 6 months on HAART and for ODs not preventable by cotrimoxazole. The HAART effect differed significantly by CD4 count stratum (P=0.02), but was significant in all strata after 6 months on HAART. In these sub-Saharan African adults, HAART initiation reduced ODs and mortality beyond that which was expected through the HAART-induced CD4+ T-cell increase. Further studies should examine practical implications of this independent 'HAART effect' on clinical outcomes in patients on HAART.

HIV-1 Associated Dementia In Pre And Post HAART Era

Patients infected with human immunodeficiency virus (HIV-1) invariably experience a wide range of neurological complications associated with AIDS that are collectively referred to as HIV associated dementia (HAD). HIV associated dementia usually develops in advanced stages of HIV-1 disease. Clinically HAD involves varying degree of neurological and psychiatric symptoms like – cognitive impairment, motor disturbances, hallucinations, delirium and behavioural changes, often leading to progressive deterioration of cognitive and motor skills. The worldwide incidence of HAD is up to 40% of AIDS population. The advent of highly active anti-retroviral therapy (HAART) had a significant negative impact on HAD, nevertheless neurological complications had shown persistence. Variability in drug penetration, distribution, drug resistance, optimal dosage levels and toxicity, hinder the success of HAART in countering the neuronal cell death or damages to the brain. In the post HAART period a subtle form of HAD has evolved which is referred as minor cognitive motor disorder (MCMD). Hence the HIV-1 induced neurological complications continue to be a clinical problem amongst AIDS affected individuals. The aim of this review is to describe the cellular and molecular basis of neuropathogenesis of HAD, list the most common therapeutic regimens used in HAART, discuss briefly the advantages and limitations of HAART agents and describe how HAD has evolved in post HAART era. doi: 10.5214/ans.0972.7531.2007.140204

Cancer Rates After Year 2000 Significantly Decrease in Children With Perinatal HIV Infection: A Study by the Italian Register for HIV Infection in Children

To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.

Effectiveness of Highly Active Antiretroviral Therapy in Reducing Heterosexual Transmission of HIV

Highly active antiretroviral therapy (HAART) has been shown to be highly effective in reducing plasma levels of HIV RNA; therefore, these treatments could diminish the risk of transmission. We analyzed 393 steady heterosexual couples, of which one partner had been previously diagnosed with HIV infection (index case) and where the nonindex partner reported his or her sexual relationship with the index case as the unique risk exposure. These couples were consecutively enrolled in the period 1991 through 2003 when the nonindex partners took their first HIV test. HIV prevalence among partners of index cases who had not received antiretroviral therapy was 8.6%, whereas no partner was infected in couples in which the index case had been treated with HAART (P = 0.0123). HIV prevalence among nonindex partners declined from 10.3% during the pre-HAART period (1991-1995) to 1.9% during the late HAART period (1999-2003; P = 0.0061). In the multivariate analysis, this decline held (odds ratio = 0.14, 95% confidence interval: 0.03-0.66) after adjusting for length of partnership, unprotected coitus, and pregnancies as well as gender, CD4 lymphocyte count, AIDS-defining diseases, and sexually transmitted infections in the index case. When HAART became widely available, a reduction of approximately 80% in heterosexual transmission of HIV was observed, irrespective of changes in other factors that affect transmission.