Lower Baseline CD4 Cell Count Research Articles

Reply to Tsai et al

To the Editor—Tsai et al identified chronic hepatitis B virus (HBV) infection as a predictor of immunologic progression in their evaluation of chronically HBV-infected individuals with primary HIV infection who did not receive antiretroviral therapy (ART) [1]. Their findings support those from our study [2], which demonstrated the negative impact of chronic HBV infection on an AIDS or death event, thereby supporting the need for improved diagnosis, prevention and treatment of HBV infection in HIV-infected patients. They also found that lower baseline CD4 cell count was an independent predictor, which agrees with our findings of lower CD4 cell count (baseline and time-updated nadir) associated with HIV disease progression and risk of death [2]. The role of HBV-active ART in HBV/HIV coinfection management is highlighted by the importance of immune restoration in hepatitis B surface antigen clearance [3]. The movement of HIV treatment guidelines toward recommending ART for all persons with HIV infection and those with early (acute or recent) HIVinfection (BII) also underscores the importance of determining HBV status in all HIV-infected patients to optimize treatment for both viruses [4]. The findings of accelerated immunologic progression, among the other negative consequences of chronic HBV infection on HIV, warrant continued investigation into the pathogenesis of HBV effects on HIV progression and immune dysfunction.

Predictors of Change in CD4 Lymphocyte Count and Weight among HIV Infected Patients on Anti-Retroviral Treatment in Ethiopia: A Retrospective Longitudinal Study

BackgroundAntiretroviral treatment (ART) has been introduced in Ethiopia a decade ago and continues to be scaled up. However, there is dearth of literature on the impact of ART on changes in CD4 lymphocyte count and weight among patients on treatment.ObjectiveTo determine the predictors of change in CD4 lymphocyte count and weight among HIV/AIDS infected patients taking antiretroviral treatment in eastern Ethiopia.MethodsA retrospective cohort study was conducted among HIV/AIDS patients taking ART from 2005 to 2010. A sample of 1540 HIV infected adult patients who started antiretroviral therapy in hospitals located in eastern Ethiopia were included in the study. The primary outcomes of interest were changes in CD4 count and weight. Descriptive statistics and multivariable regression analyses were performed to examine the outcomes among the cohort.ResultsBoth the median CD4 lymphocyte counts and weight showed improvements in the follow up periods. The multivariate analysis shows that the duration of ART was an important predictor of improvements in CD4 lymphocyte count (beta 7.91; 95% CI 7.48–8.34; p 0.000) and weight (beta 0.15; 95% CI 0.13–0.18; p 0.000). Advanced WHO clinical stage, lower baseline CD4 cell count, and baseline hemoglobin levels were factors associated with decline in weight. Actively working patients had higher CD4 lymphocyte count and weight compared to those that were ambulatory (p<0.05).ConclusionWe detected a substantial increment in weight and CD4 lymphocyte count among the patients who were taking ART in eastern Ethiopia. Patients who are of older age, with low initial CD4 lymphocyte count, late stage of the WHO clinical stages and lower hemoglobin level may need special attention. The reasons for the improved findings on CD4 count and weight throughout the five years of follow up merit further investigation.

Earlier initiation of antiretroviral therapy, increased tuberculosis case finding and reduced mortality in a setting of improved HIV care: a retrospective cohort study

High early mortality after antiretroviral therapy (ART) initiation in resource-limited settings is associated with low baseline CD4 cell counts and a high burden of opportunistic infections. Our large urban HIV clinic in Uganda has made concerted efforts to initiate ART at higher CD4 cell counts and to improve diagnosis and care of patients coinfected with tuberculosis (TB). We sought to determine associated treatment outcomes. Routinely collected data for all patients who initiated ART from 2005 to 2009 were analysed. Median baseline CD4 cell counts by year of ART initiation were compared using the Cuzick test for trend. Mortality and TB incidence rates in the first year of ART were computed. Hazard ratios (HRs) were calculated using multivariable Cox proportional hazards models. First-line ART was initiated in 7659 patients; 64% were women, and the mean age was 37 years (standard deviation 9 years). Median baseline CD4 counts increased from 2005 to 2009 [82 cells/μL (interquartile range (IQR) 24, 153) to 148 cells/μL (IQR 61, 197), respectively; P<0.001]. The mortality rate fell from 6.5/100 person-years at risk (PYAR) [95% confidence interval (CI) 5.5-7.6 PYAR] to 3.6/100 PYAR (95% CI 2.2-5.8 PYAR). TB incidence rates increased from 8.2/100 PYAR (95% CI 7.1-9.5 PYAR) to 15.6/100 PYAR (95% CI 12.4-19.7 PYAR). A later year of ART initiation was independently associated with decreased mortality (HR 0.91; 95% CI 0.83-1.00; P=0.04). Baseline CD4 cell counts have increased over time and are associated with decreased mortality. Additional reductions in mortality might be a result of a better standard of care and increased TB case finding. Further efforts to initiate ART earlier should be prioritized even in a setting of capped or reduced funding for ART programmes.

Early Mortality in Adults Initiating Antiretroviral Therapy (ART) in Low- and Middle-Income Countries (LMIC): A Systematic Review and Meta-Analysis

BackgroundWe systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART) initiation in low- and middle-income countries (LMIC) in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known.Methods and FindingsStudies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76%) from sub-Saharan Africa (SSA), 5 (10%) from Asia, 2 (4%) from the Americas, and 5 (10%) were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3–55 months and 11–192 cells/mm3, respectively. Loss-to-follow-up, reported in 40 (80%) studies, ranged from 0.3%–27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11–0.24) versus 0.11 (95% CI 0.10–0.13) for Asia, and 0.07 (95% CI 0.007–0.20) for the Americas. Of 14 (28%) studies reporting cause-specific mortality, tuberculosis (TB) (5%–44%), wasting (5%–53%), advanced HIV (20%–37%), and chronic diarrhea (10%–25%) were most common. Independent factors associated with early mortality in 30 (60%) studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA.ConclusionsSignificant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early death are urgently needed.

Incidence and risk factors of antiretroviral treatment failure in treatment-naïve HIV-infected patients at Chiang Mai University Hospital, Thailand

BackgroundThe use of combination antiretroviral therapy (cART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to determine the incidence and risk factors of treatment failure in a cohort of treatment-naïve Thai HIV-infected patients.MethodsA retrospective cohort study was conducted among HIV-infected patients initiating their first cART at Chiang Mai University Hospital, Thailand.ResultsFrom January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean age was 37.9 ± 8.6 years. The median baseline CD4 count was 57.7 cells/mm3 (IQR 22, 127). GPO-VIR® (a fixed-dose combination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients, 83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of virological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest predictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed immunological failure. A low CD4 cell count at baseline (< 100 cells/mm3) and the increment of CD4 cell count of < 50 cell/mm3 after 6 months of cART were the predictors for immunological failure (p < 0.001).ConclusionsThis study demonstrated that even in resource-limited settings, the high rate of success could be expected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline CD4 cell count are the predictors for unfavorable outcome of cART.

The effect of injecting drug use history on disease progression and death among HIV‐positive individuals initiating combination antiretroviral therapy: collaborative cohort analysis

We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART). The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated and compared using methods that allow for competing risks. Data on 6269 IDUs and 37 774 non-IDUs were analysed. Compared with non-IDUs, a lower proportion of IDUs initiated cART with a CD4 cell count <200 cells/μL or had a prior diagnosis of AIDS. Mortality rates were higher in IDUs than in non-IDUs (2.08 vs. 1.04 per 100 person-years, respectively; P<0.001). Lower baseline CD4 cell count, higher baseline HIV viral load, clinical AIDS at baseline, and later year of cART initiation were associated with disease progression in both groups. However, the inverse association of baseline CD4 cell count with AIDS and death appeared stronger in non-IDUs than in IDUs. The risk of death from each specific cause was higher in IDUs than non-IDUs, with particularly marked increases in risk for liver-related deaths, and those from violence and non-AIDS infection. While liver-related deaths and deaths from direct effects of substance abuse appear to explain much of the excess mortality in IDUs, they are at increased risk for many other causes of death, which may relate to suboptimal management of HIV disease in these individuals.

Ophthalmic manifestations and risk factors for mortality of HIV patients in the post-highly active anti-retroviral therapy era

To evaluate the ophthalmic manifestations and risk factors for mortality in HIV patients in the post-highly active anti-retrovirus therapy (HAART) era. Retrospective study. 151 patients with HIV infection. Review of all HIV patients who have attended the Hong Kong Eye Hospital between 2000 and 2007. Ocular findings especially opportunistic infections and medical information including mortality during follow up. At presentation, 139 (92.1%) patients were already diagnosed with HIV and 58 (41.7%) had an AIDS indicator condition. Fifty-one (33.8%) patients had HIV-related eye disease on presentation and the leading manifestations were cytomegalovirus (CMV) retinitis and HIV microangiopathy. Low baseline CD4 cell count <100 cells/L was significantly related with HIV-related ophthalmic manifestations and CMV retinitis at presentation (P < 0.013). 105 patients were followed for 6 months or more and the mean follow-up was 4.8 years. There was no significant change in visual acuity compared with baseline (P = 0.13). 20 (19.0%) patients had one eye with final visual acuity of 20/200 or worse and the leading cause for poor vision was CMV retinitis. 11 (10.5%) patients died during the follow-up due to complications of HIV/AIDS. The presence of HIV retinal microangiopathy was significantly associated with mortality (P = 0.005). CMV retinitis remains the main HIV-related ocular disease in the post-HAART era. HIV retinal microangiopathy might be an important prognostic factor for mortality. Appropriate ophthalmic monitoring is justified to detect for ophthalmic complications in HIV patients regardless of HAART use in order for prompt initiation of treatment.

Bone mineral density changes in protease inhibitor-sparing vs. nucleoside reverse transcriptase inhibitor-sparing highly active antiretroviral therapy: data from a randomized trial*

The aim of the study was to compare changes in bone mineral density (BMD) over 144 weeks in HIV-infected patients initiating nucleoside reverse transcriptase inhibitor (NRTI)-sparing or protease inhibitor-sparing highly active antiretroviral therapy (HAART). Sixty-three HAART-naïve patients were randomized to zidovudine/lamivudine+efavirenz or lopinavir/ritonavir+efavirenz. We performed dual energy X-ray absorptiometry (DEXA) at baseline and at weeks 24, 48, 96 and 144 to evaluate lumbar spine and femoral neck (hip) BMD. At baseline, 33 patients (55.9%) had low BMD (T-score < -1.0) and of these eight had osteoporosis (T-score < -2.5). Spine BMD declined in both arms until week 24, before stabilizing. In the NRTI-sparing arm, the mean percentage change from baseline was -2.7% [95% confidence interval (CI) -3.9 to -1.4] at week 24 and -2.5% (95% CI -5.4 to 0.3) at week 144, compared with -3.2% (95% CI -4.4 to -2.1) and -1.9% (95% CI -3.5 to -0.3) in the protease inhibitor-sparing arm. Hip BMD declined until week 48 before stabilizing. In the NRTI-sparing arm, BMD had decreased by -5.1% (95% CI -7.1 to -3.1) at week 48 and -4.5% (95% CI -6.9 to -2.1) at week 144, compared with -6.1% (95% CI -8.2 to -4.0) and -5.0% (95% CI -6.8 to -3.1) in the protease inhibitor-sparing arm. There were no significant differences between arms. Low baseline CD4 cell count was independently associated with spine (P=0.007) and hip (P=0.04) BMD loss and low body mass index with hip BMD loss (P=0.03). Spine and hip BMD declined rapidly 24 to 48 weeks after initiating HAART, independent of the assigned drug class, but thereafter BMD values remained stable.

Genetic Factors Influencing Severe Atazanavir‐Associated Hyperbilirubinemia in a Population with Low UDP‐Glucuronosyltransferase 1A1*28 Allele Frequency

High prevalence of severe atazanavir-associated hyperbilirubinemia in Asians with low prevalence of the UDP-glucuronosyltransferase (UGT)1A1*28 polymorphism suggests the importance of genetic factors other than UGT1A1*28 for atazanavir-associated hyperbilirubinemia in these populations. Serum bilirubin levels were measured in 129 Korean human immunodeficiency virus-infected patients 3 months after initiation of atazanavir (400 mg per day) with good adherence to medication. The multidrug resistance gene 1 (MDR1) C3435T and G2677T/A variations and UGT1A1*6 and *28 were examined by direct sequencing of DNA from peripheral whole blood samples. The associations between genetic polymorphisms and severe (grade 3-4) hyperbilirubinemia were evaluated using multivariate logistic regression analysis including demographic and clinical variables. The median patient age was 39 years (interquartile range, 34-51 years), and 91% were men. At baseline, the median CD4 cell count was 261 cells/microL (interquartile range, 181-405 cells/microL). Severe hyperbilirubinemia was detected in 27 patients (21%). The independent risk factors for severe hyperbilirubinemia were low baseline CD4 cell count (adjusted odds ratio per 10 cells/microL increase, 0.97; 95% confidence interval, 0.94-0.99), UGT1A1*28 (adjusted odds ratio, 4.15; 95% confidence interval, 1.46-11.84), and MDR1 G2677T/A (adjusted odds ratio, 9.65; 95% confidence interval, 1.09-85.61). Of 19 patients with wild-type alleles for both MDR1 2677 and UGT1A1*28, none developed severe hyperbilirubinemia. The MDR1 G2677T/A variation and UGT1A1*28 are independent risk factors for severe atazanavir-associated hyperbilirubinemia in Korean human immunodeficiency virus-infected patients.

State of the ART: clinical efficacy and improved quality of life in the public antiretroviral therapy program, Free State province, South Africa

The South African public-sector antiretroviral treatment (ART) program has yielded promising early results. To extend and reinforce these preliminary findings, we undertook a detailed assessment of the clinical efficacy and outcomes over two years of ART. The primary objective was to assess the clinical outcomes and adverse effects of two years of ART, while identifying the possible effects of baseline health and patient characteristics. A secondary objective was to address the interplay between positive and negative outcomes (clinical benefits versus adverse effects) in terms of the patients’ physical and emotional quality of life (QoL). Clinical outcome, baseline characteristics, health status, and physical and emotional QoL scores were determined from clinical files and interviews with 268 patients enrolled in the Free State ART program at three time points (6, 12, and 24 months of ART). Age, sex, education, and baseline health (CD4 cell count and viral load) were all independently associated with the ART outcome in the early stages of treatment, but their impact diminished as the treatment progressed. The number of patients classified as treatment successes increased over the first two years of ART, whereas the proportion of patients experiencing adverse effects diminished. Importantly, our findings show that ART had strong and stable positive effects on physical and emotional QoL. These favorable results demonstrate that a well-managed public-sector ART program can be very successful within a high-HIV-prevalence resource-limited setting. This finding emphasizes the need to adopt treatment scale-up as a key policy priority, while at the same time ensuring that the highest standards of healthcare provision are maintained. Healthcare services should also target vulnerable groups (males, less-educated patients, those with low baseline CD4 cell counts, and high baseline viral loads) who are most likely to experience treatment failure.

Natural History of Compensated Hepatitis C Virus–Related Cirrhosis in HIV‐Infected Patients

To provide information about the incidence and predictors of liver decompensation and death due to liver failure in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. Prospective cohort study of 154 HIV-HCV-coinfected patients with a new diagnosis of Child-Pugh-Turcotte (CPT) class A compensated cirrhosis. We evaluated time from diagnosis to the first liver decompensation and death from liver disease, as well as predictors of these outcomes. Thirty-six patients (23.4%) developed liver decompensation. The incidence of liver decompensation was 6.40 cases per 100 person-years (95% confidence interval [CI], 4.18-9.38 cases per 100 person-years). Factors independently associated with liver decompensation were lack of HCV therapy (hazard ratio [HR], 3.38; 95% CI, 1.09-10.53; P = .035), baseline CD4 cell counts <or=300 cells/mm3 (HR, 2.12; 95% CI, 1.14-5.04; P = .021), CPT score 6 versus 5 (HR, 3.33; 95% CI, 1.39-7.69; P = .007), and a diagnosis of cirrhosis based on data other than biopsy or transient elastography (HR, 2.09; 95% CI, 1.05-4.16; P = .036 ). Fifteen patients (9.7%) died; 11 (73%) of these 15 died from liver disease (mortality due to liver failure, 2.44 deaths per 100 person-years; 95% CI, 1.21-4.36 deaths per 100 person-years). Hepatic encephalopathy as the first liver decompensation (HR, 20.67; 95% CI, 2.71-157.57; P = .003), baseline CD4 count <or=300/mm3 (HR, 0.24; 95% CI, 0.07-0.78; P = 0.17), and baseline CPT score 6 (HR, 4.50; 95% CI, 1.63-12.37; P = .004) were independently associated with liver-related death. The incidence of clinical liver events in HIV-HCV-coinfected patients with CPT class A compensated cirrhosis is close to that previously reported in HCV-monoinfected patients. Lower baseline CD4 cell counts, lack of therapy against HCV, and higher CPT score are the factors related to the occurrence of clinical liver events. Minimal changes in CPT score have strong impact in the prognosis of this population.

Long-Term Patterns in CD4 Response Are Determined by an Interaction Between Baseline CD4 Cell Count, Viral Load, and Time: The Asia Pacific HIV Observational Database (APHOD)

Random effects models were used to explore how the shape of CD4 cell count responses after commencing combination antiretroviral therapy (cART) develop over time and, in particular, the role of baseline and follow-up covariates. Patients in Asia Pacific HIV Observational Database who first commenced cART after January 1, 1997, and who had a baseline CD4 cell count and viral load measure and at least 1 follow-up measure between 6 and 24 months, were included. CD4 cell counts were determined at every 6-month period after the commencement of cART for up to 6 years. A total of 1638 patients fulfilled the inclusion criteria with a median follow-up time of 58 months. Lower post-cART mean CD4 cell counts were found to be associated with increasing age (P < 0.001), pre-cART hepatitis C coinfection (P = 0.038), prior AIDS (P = 0.019), baseline viral load < or equal to 100,000 copies per milliliter (P < 0.001), and the Asia Pacific region compared with Australia (P = 0.005). A highly significant 3-way interaction between the effects of time, baseline CD4 cell count, and post-cART viral burden (P < 0.0001) was demonstrated. Higher long-term mean CD4 cell counts were associated with lower baseline CD4 cell count and consistently undetectable viral loads. Among patients with consistently detectable viral load, CD4 cell counts seemed to converge for all baseline CD4 levels. Our analysis suggest that the long-term shape of post-cART CD4 cell count changes depends only on a 3-way interaction between baseline CD4 cell count, viral load response, and time.

Incidence and Predictors of Death, Retention, and Switch to Second‐Line Regimens in Antiretroviral‐Treated Patients in Sub‐Saharan African Sites with Comprehensive Monitoring Availability

Antiretroviral treatment programs in sub-Saharan Africa have high rates of early mortality and loss to follow-up. Switching to second-line regimens is often delayed because of limited access to laboratory monitoring. Retrospective analysis was performed of a cohort of adults who initiated a standard first-line antiretroviral treatment at 5 public sector sites in 3 African countries. Monitoring included routine CD4 cell counts, human immunodeficiency virus RNA measures, and records of whether appointments were kept. Incidence and predictors of death, loss to follow-up, and switch to second-line regimens were analyzed by time-to-event approaches. A total of 3749 patients were analyzed; at baseline, 37.1% were classified as having World Health Organization disease stage 3 or 4, and the median CD4 cell count was 192 cells/mL. First-line regimens were nevirapine based in 96.5% of patients; 17.7% of patients attended <95% of their drug pickup appointments. During 4545 person-years of follow-up, mortality was 8.6 deaths per 100 person-years and was predicted by lower baseline CD4 cell count, lower hemoglobin level, and lower body mass index (calculated as weight in kilograms divided by the square of height in meters); more-advanced clinical stage of infection; male sex; and more missed drug pickup appointments. Dropouts (which accrued at a rate of 2.1 dropouts per 100 person-years) were predicted by a lower body mass index, more missed visits and missed drug pickup appointments, and later calendar year. Incidence of switches to second-line regimens was 4.9 per 100 person-years; increased hazards were observed with lower CD4 cell count and earlier calendar year at baseline. In patients who switched, virological failure was predicted by combined clinical and CD4 criteria with 74% sensitivity and 30% specificity. In an antiretroviral treatment program employing comprehensive monitoring, the probability of switching to second-line therapy was limited. Regular pickup of medication was a predictor of survival and was also strongly predictive of patient retention.

CORRELATION BETWEEN BASELINE CD4+ T-LYMPHOCYTE COUNT AND PLASMA VIRAL LOAD IN AIDS PATIENTS AND THEIR EARLY CLINICAL AND IMMUNOLOGICAL RESPONSE TO HAART: A PRELIMINARY STUDY

The aim of this study was to determine the clinical, immunological and virological status of newly diagnosed AIDS cases and to monitor their clinical and immunological response to HAART after a minimum period of three months. Forty three drug naive AIDS patients were enrolled. The most common presenting complaints were weight loss (74.4%), cough (72.1%) and diarrhoea (67.4%). Mean baseline CD4 cell count was 112 ±60 cells/μL and mean baseline plasma viral load of 31 patients studied was 192,686 copies/mL. Baseline plasma viral load was higher among patients with lower baseline CD4 cell count. During follow-up, 80.8% patients showed clinical improvement, while a CD4 cell count increased by ≥50 cells/μL in 84.6% cases. Mean CD4 cell count increased from 126 ±16.6 cells/μL at baseline to 278 ±196.7 cells/μL.

Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

<h2>Summary</h2><h3>Background</h3> Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. <h3>Methods</h3> The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, and stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude mortality rates were also calculated. <h3>Findings</h3> 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, respectively. 2056 (4·7%) deaths were observed during the study period, with crude mortality rates decreasing from 16·3 deaths per 1000 person-years in 1996–99 to 10·0 deaths per 1000 person-years in 2003–05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36·1 (SE 0·6) years to 49·4 (0·5) years. Women had higher life expectancies than did men. Patients with presumed transmission via injecting drug use had lower life expectancies than did those from other transmission groups (32·6 [1·1] years <i>vs</i> 44·7 [0·3] years in 2003–05). Life expectancy was lower in patients with lower baseline CD4 cell counts than in those with higher baseline counts (32·4 [1·1] years for CD4 cell counts below 100 cells per μL <i>vs</i> 50·4 [0·4] years for counts of 200 cells per μL or more). <h3>Interpretation</h3> Life expectancy in HIV-infected patients treated with combination antiretroviral therapy increased between 1996 and 2005, although there is considerable variability between subgroups of patients. The average number of years remaining to be lived at age 20 years was about two-thirds of that in the general population in these countries. <h3>Funding</h3> UK Medical Research Council, GlaxoSmithKline.

Tolerability and Effectiveness of First-Line Regimens Combining Nevirapine and Lamivudine Plus Zidovudine or Stavudine in Cameroon

We compared the tolerability and effectiveness of two major first-line regimens used in resource-limited settings, namely zidovudine-lamivudine-nevirapine and stavudine-lamivudine-nevirapine. HIV-1-infected adults in Cameroon were enrolled in a prospective cohort study between 2001 and 2003. They were eligible if they had AIDS or a CD4 cell count below 350/mm(3), a Karnofsky score over 50%, and no contraindications to antiretroviral treatment. The patients were followed up to 2 years. Of 169 patients, 85 received zidovudine-lamivudine-nevirapine and 84 stavudine-lamivudine-nevirapine. The incidence rates of treatment changes, death, drug resistance, and severe adverse effects were, respectively, 12.0 [95% confidence interval (CI) 7.2-19.9] and 10.9 (CI 6.4-18.3) per 100 person-years; 5.7 (CI 2.8-11.4) and 7.6 (CI 4.2-13.7); 2.9 (CI 1.1-7.7) and 5.0 (CI 2.4-10.6); and 41.7 (CI 30.2-57.6) and 49.1 (CI 36.1-66.6). The Kaplan-Meier curves for the likelihood of remaining on the initial regimen (p = 0.8) and for survival (p = 0.5) did not differ significantly between the groups. In Cox multivariate analysis only a lower baseline CD4 cell count was associated with death (p < 0.001). The proportion of patients with undetectable viral load and the increase in the CD4 cell count were similar in the two groups. Anemia was rare (4% vs. 6%). Five cases of severe peripheral neuropathy and one case of lipodystrophy occurred. This study suggests that the zidovudine-lamivudine-nevirapine combination is a safe first-line treatment, even in settings with few laboratory resources. In view of stavudine toxicity, these results support recommendations calling for a gradual switch from stavudine- to zidovudine-based regimens.

Suppression of HIV-1 replication by antiretroviral therapy improves renal function in persons with low CD4 cell counts and chronic kidney disease

To examine the association between changes in glomerular filtration rates (GFR) and antiretroviral therapy (ART)-mediated suppression of plasma HIV-1 viremia. : Observational, prospective, multicenter cohort study. ART regimens or treatment strategies in HIV-1-infected subjects were implemented through randomized clinical trials; 1776 ambulatory subjects from these trials also enrolled in this cohort study. The association between suppression of viremia and GFR changes from baseline was examined using the abbreviated Modification of Diet and Renal Disease equation in mixed effects linear models. GFR improvement was associated with ART-mediated suppression of plasma viremia in subjects with both chronic kidney disease stage > or = 2 and low baseline CD4 cell counts (< 200 cells/microl). In this subset, viral suppression (by > 1.0 log10 copies/ml or to < 400 copies/ml) was associated with an average increase in GFR of 9.2 ml/min per 1.73 m(2) from baseline (95% confidence interval, 1.6-16.8; P = 0.02) over a median follow-up of 160 weeks. The magnitude of this association increased in subjects who had greater baseline impairment of renal function, and it did not depend on race or sex. Viral suppression was associated with GFR improvements in those with both low CD4 cell counts and impaired baseline renal function, supporting an independent contribution of HIV-1 replication to chronic renal dysfunction in advanced HIV disease. GFR improvement not associated with viral suppression also was observed in subjects with higher CD4 cell counts.

Active Tuberculosis Does Not Always Imply the Initiation of Highly Active Antiretroviral Therapy in HIV-Infected Patients

Infection with HIV is an important risk factor for tuberculosis (TB). One-half million cases of TB attributable to HIV infection occur worldwide each year. Since the advent of highly active antiretroviral therapy (HAART) the morbidity and mortality of HIV-infected patients have declined. However concomitant TB treatment and HAART are hampered by a high pill burden complex drug interactions treatment-related adverse events and paradoxic reactions. Studies that have assessed the effect of HAART in the course of TB and HIV coinfection are few. All these retrospective studies suggest that coinfected patients with a CD4 count less than 100 cells/mm/3 would probably benefit from early initiation of HAART. Unlike other HIV-associated opportunistic infections TB may occur at high CD4 cell counts. The indication for HAART in these particular cases has not been assessed and current antiretroviral (ARV) treatment guidelines are based on expert opinion. We evaluated retrospectively 93 episodes of TB diagnosed in 87 HIV-infected patients from January 2000 to February 2004 at Bichat Hospital in an attempt to assess the clinical aspects and outcome of TB according to the level of immunosuppression at TB diagnosis and to the prescription of HAART in the course of TB treatment. (excerpt)

Effectiveness and metabolic complications after 96 weeks of a generic fixed-dose combination of stavudine, lamivudine, and nevirapine among antiretroviral-naive advanced HIV-infected patients in Thailand: A prospective study

Background: Generic fixed-dose combination (FDC) antiretroviral therapy (ART) has been widely used in resource-limited settings. Treatment based on these combinations provide low pill burden and are less expensive. Objective: The aim of this study was to determine the long-term effectiveness and metabolic complications of a generic FDC of stavudine (d4T)/lamivudine (3TC)/ nevirapine (NVP), among ART-naive HIV-infected patients. Methods: A prospective study was conducted among patients who were initiated on d4T/3TC/NVP between November 2004 and March 2005. Plasma HIV-1 RNA, CD4 and alanine transaminase were assessed every 12 weeks. Fasting plasma glucose (FPG) and lipid profile were determined at 96 weeks. Adverse events and genotypic drug resistance were recorded. The primary outcome of interest was the proportion of patients who achieved plasma HIV-1 RNA <50 copies/mL after 96 weeks of ART and analyzed by intent-to-treat (ITT) and on-treatment (OT) populations. Results: There were 140 patients (mean [SD] age, 35.7 [7.6] years; male, 67.9%) enrolled in the study. Median (interquartile range [IQR]) baseline CD4 was 31 (14–79) cells/mm 3 and HIV-1 RNA count was 433,500 (169,000–750,000) copies/mL. At week 96, 87 patients (ITT, 62.1%; OT, 87.0%) achieved HIV-1 RNA –50 copies/mL. Median (IQR) CD4 at 96 weeks was 328 (229–450) cells/mm 3. The reasons for drug discontinuation were as follows: drug resistance (9.3%), lost to follow-up (9.3%), NVP- related rashes (7.9%), death (5.0%), d4T-related adverse events (3.6%), and transferred to another hospital (2.1%). At 96 weeks, 25 patients (28.7%) had low-density lipoprotein cholesterol (LDL-C) >130 mg/dL, 7 (8.0%) had LDL-C >160 mg/dL, 6 (6.9%) had triglycerides >400 mg/dL, and 2 (2.3%) had FPG >126 mg/dL. Eleven patients (12.6%) had a lactic acid level >2.5 mmol/L. Eight patients (9.2%) needed to take antihypertensive agents. Of 13 patients who developed virologic failure, 76.9% and 61.5% had M184V/I and Y181C/I mutations, respectively. Conclusions: Initiation of this FDC ofd4T/3TC/NVP in these ART-naive patients with advanced HIV infection and low baseline CD4 cell count was effective at 96 weeks of follow-up with regard to virologic and immunologic responses. However, long-term metabolic complications, particularly dyslipidemia, were common and should be closely monitored.

Correlation between baseline CD4&lt;sup&gt; +&lt;/sup&gt; T-Lymphocyte count and plasma viral load in AIDS patients and their early clinical and immunological response to HAART: A preliminary study

The aim of this study was to determine the clinical, immunological and virological status of newly diagnosed AIDS cases and to monitor their clinical and immunological response to HAART after a minimum period of three months. Forty three drug naive AIDS patients were enrolled. The most common presenting complaints were weight loss (74.4%), cough (72.1%) and diarrhoea (67.4%). Mean baseline CD4 cell count was 112 +/- 60 cells/microL and mean baseline plasma viral load of 31 patients studied was 192,686 copies/mL. Baseline plasma viral load was higher among patients with lower baseline CD4 cell count. During follow-up, 80.8% patients showed clinical improvement, while a CD4 cell count increased by > or =50 cells/microL in 84.6% cases. Mean CD4 cell count increased from 126 +/- 16.6 cells/microL at baseline to 278 +/- 196.7 cells/microL.