First Year Of Antiretroviral Treatment Research Articles

Changes in Body Mass Index after Initiation of Antiretroviral Treatment: Differences by Class of Core Drug.

Recent research on antiretroviral treatment (ART) for HIV suggests that integrase strand transfer inhibitors (INSTIs) cause faster weight gain compared to other drug classes. Here, we investigated changes in body mass index (BMI) and obesity prevalence after treatment initiation and corresponding differences between drug classes. Data were derived from a large collaborative cohort in Greece. Included individuals were adults who started ART, in or after 2010, while previously ART naïve and achieved virologic response within the first year of ART. Data were analysed using mixed fractional polynomial models. INSTI regimens led to the more pronounced BMI increases, followed by boosted PI and NNRTI based regimens. Individuals with normal initial BMI are expected to gain 6 kg with an INSTI regimen compared to 4 kg with a boosted PI and less than 3 kg with a NNRTI regimen after four years of treatment. Prevalence of obesity was 5.7% at ART initiation and 12.2%, 14.2% and 18.1% after four years of treatment with NNRTIs, PIs, and INSTIs, respectively. Dolutegravir or Raltegravir were associated with marginally faster BMI increase compared to Elvitegravir. INSTIs are associated with faster weight gain. INSTIs’ increased risk of treatment emergent obesity and, possibly, weight-related co-morbidities should be judged against their improved efficacy and tolerability but increased clinical attention is required.

Analysis on mortality in HIV/AIDS cases aged 15 years and older under antiretroviral treatment in Henan province, 2002-2019

Objective: To analyze the mortality in HIV/AIDS cases aged ≥15 years under antiretroviral treatment (ART) in Henan province from 2002 to 2019, and provide evidence for reducing the mortality rate of HIV/AIDS and AIDS prevention and treatment. Methods: Data of HIV/AIDS cases aged ≥15 years who received ART in Henan from 2002 to 2019 were obtained from "Infectious Disease Surveillance System - Basic Information on AIDS Prevention and Control". In this retrospective study, Cox proportional risk model was used to analyze the influencing factors for HIV/AIDS related deaths. Software SPSS 23.0 was used for statistical analysis. Results: From 2002 to 2019, a total of 72 986 HIV/AIDS cases aged ≥15 years received ART, in whom, 16 634 died during this period. Most of the death cases were aged ≥40 years old (68.5%,11 393/16 634), males (62.6%,10 419/16 634), infected through blood-borne transmission (71.7%,11 927/16 634), and farmers or migrant workers (91.7%,15 249/16 634). Most of the deaths were due to AIDS related diseases (73.7%, 12 261/16 634), and the case fatality rate was 16.8% (12 261/72 986). A total of 34.6% (4 237/12 261) of HIV/AIDS cases died of AIDS-related diseases in the first year of ART, and the cumulative survival rates at 10 and 18 years of ART were 78.3% and 71.8%, respectively. The proportion of the HIV/AIDS cases with baseline CD4+T lymphocyte (CD4) counts <200 cells/μl at age 15 years when ART started was 45.5% (30 432/66 898). Cox proportional risk regression model showed that, compared with the cases with baseline CD4 counts ≥350 cells/μl, the risk of death was 1.78 times higher than in the cases with CD4 counts <200 cells/μl (95%CI: 1.64-1.94) and 1.24 times higher in the cases with CD4 counts ≥200 cells/μl (95%CI: 1.13-1.36), respectively. The risk of death in symptomatic cases at baseline survey was 1.25 times higher than that in asymptomatic cases (95%CI: 1.16-1.35). The cases with a latest viral load ≥1 000 copies/ml had 7.09 times higher risk of death than those with a last viral load<1 000 copies/ml (95%CI: 6.65-7.54). Conclusions: The majority of HIV/AIDS deaths occurred in the cases aged ≥15 years receiving ART in Henan province during 2002-2019, who were infected through blood-borne transmission and farmers/migrant workers, and AIDS-related diseases were the main causes of the deaths. With the gradual implementation of ART policy, the high survival rate in HIV/AIDS cases can be maintained for a long time in Henan. To reduce the case fatality rate and improve the quality of life of HIV/AIDS patients, CD4 counts test should be further strengthened and eligible HIV/AIDS patients should be covered by standard ART in a timely manner.

High conversion of tuberculin skin tests during the first year of antiretroviral treatment among South African adults in primary care.

Anergy reduces the sensitivity of the tuberculin skin test (TST) to detect Mycobacterium tuberculosis infection in people living with HIV. Antiretroviral treatment (ART) can reverse TST anergy, but data is scarce. To estimate TST conversion rates and factors associated with TST conversion, TST was placed at ART initiation, and 6 and 12 months thereafter (if TST negative at prior assessment). Of 328 ART-eligible participants, 70% (231/328) had a valid TST result of whom 78% (180/231) were TST negative. At 6-month follow-up, 22% (24/109, 95% confidence interval [CI] 15%, 31%) of participants on ART, without incident tuberculosis (TB), and with a valid TST result converted to a positive TST. Of these 109 individuals, those with baseline CD4+ cell count >250 cells/μl were more likely to TST convert compared to those with baseline CD4+ cell count ≤250 cells/μl (odds ratio [OR] 3.54, 95% CI 1.29, 11.47). At 12 months post-ART initiation, an additional 12% (9/78, 95% CI 6, 20) of participants on ART, without incident TB and with a valid TST result experienced TST conversion. After 1 year on ART, TST conversion rate was 38 per 100 person-years (95% CI 26, 52), and lower in individuals with baseline CD4+ cell count ≤250 cells/μl (23/100 person-years, 95% CI 11, 41) compared to those with baseline CD4+ cell count >250 cells/μl (50/100 person-years, 95% CI 32, 73). TST conversion rate in the first year of ART is high, especially among people with CD4+ cell count >250 cells/μl. A TST-based eligibility strategy at ART initiation may underestimate eligibility for preventive therapy for tuberculosis.

Drug Resistance in HIV-Positive Adults During the Initial Year of Antiretroviral Treatment at Ethiopian Health Centers.

BackgroundThe increasing prevalence of antiretroviral drug resistance in Sub-Saharan Africa threatens the success of HIV programs. We have characterized patterns of drug resistance mutations (DRMs) during the initial year of antiretroviral treatment (ART) in HIV-positive adults receiving care at Ethiopian health centers and investigated the impact of tuberculosis on DRM acquisition.MethodsParticipants were identified from a cohort of ART-naïve individuals aged ≥18 years, all of whom had been investigated for active tuberculosis at inclusion. Individuals with viral load (VL) data at 6 and/or 12 months after ART initiation were selected for this study. Genotypic testing was performed on samples with VLs ≥500 copies/mL obtained on these occasions and on pre-ART samples from those with detectable DRMs during ART. Logistic regression analysis was used to investigate the association between DRM acquisition and tuberculosis.ResultsAmong 621 included individuals (110 [17.5%] with concomitant tuberculosis), 101/621 (16.3%) had a VL ≥500 copies/mL at 6 and/or 12 months. DRMs were detected in 64/98 cases with successful genotyping (65.3%). DRMs were detected in 7/56 (12.5%) pre-ART samples from these individuals. High pre-ART VL and low mid-upper arm circumference were associated with increased risk of DRM acquisition, whereas no such association was found for concomitant tuberculosis.ConclusionsAmong adults receiving health center–based ART in Ethiopia, most patients without virological suppression during the first year of ART had detectable DRM. Acquisition of DRM during this period was the dominant cause of antiretroviral drug resistance in this setting. Tuberculosis did not increase the risk of DRM acquisition.

Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir

BackgroundLimited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF.MethodsHIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen.ResultOf 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (− 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen.ConclusionRenal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.

Incidence of Tuberculosis During the First Year of Antiretroviral Treatment in West African HIV-Infected Adults.

We estimated tuberculosis incidence during the first year on antriretroviral therapy without isoniazid-preventive treatment in 6938 West African HIV-infected adults at 3.33 cases per 100 person-years (95% CI, 2.85–3.80). In multivariate Poisson models, sites in Cote d’Ivoire, male gender, low body mass index, low hemoglobin, low CD4 count, and young age were significantly associated with higher incidence.

Chronic kidney disease and HIV in the era of antiretroviral treatment: findings from a 10-year cohort study in a west African setting

BackgroundIt has been reported that people living with HIV in West Africa exhibited the highest risks for chronic kidney disease (CKD) in the world. Here, we aimed at determining the CKD frequency and changes in kidney function during antiretroviral treatment (ART) in a large cohort of HIV-patients followed in Burkina Faso.MethodsWe included ART-naive adults who initiated ART at the Day Care Unit of the Souro Sanou University Hospital between 01/01/2007 and 12/31/2016. We assessed the estimated glomerular filtration rate (eGFR) by serum creatinine using the Modification of Diet in Renal Disease (MDRD) equation. Following the K/DOQI recommendations, CKD was defined as eGFR < 60 ml/min/1.73m2 at two consecutive measurements at least 3 months apart. The factors associated with eGFR decline or CKD were identified by mixed linear regression and Cox regression, respectively.ResultsThree thousand, one hundred and thirty-eight patients (72% women) were followed for a median (IQR) of 4.5(2.2–6.9) years. At baseline, median eGFR (IQR) was 110.7(94.4–128.4) ml/min/1.73m2 and 93 (3%) patients exhibited eGFR < 60 ml/min/1.73m2. The lowest-performing progressions of eGFR during the first year of ART were observed in patients with 40-49 yr. age range (− 8.3[− 11.7;-5.0] ml/min/1.73m2, p < 0.001), age ≥ 50 yr. (− 6.2[− 10.7;-1.8] ml/min/1.73m2, p = 0.006) and high blood pressure (HBP) (− 28.4[− 46.9;-9.9] ml/min/1.73m2, p = 0.003) at ART initiation. Regarding the ART exposure in patients with normal baseline eGFR, zidovudine (AZT) with protease inhibitor (PI) (− 4.7[− 7.7;-1.6] ml/min/1.73m2, p = 0.002), tenofovir (TDF) + PI (− 13.1[− 17.4;-8.7] ml/min/1.73m2, p < 0.001), TDF without PI (− 3.2[− 5.0;-1.4] ml/min/1.73m2, p < 0.001), stavudine (d4T) + PI (− 8.5[− 14.6–2.4] ml/min/1.73m2, p = 0.006) and d4T without PI (− 5.0[− 7.6–2.4] ml/min/1.73m2, p < 0.001) were associated with poorer eGFR progression. The prevalence of CKD was 0.5% and the incidence was 1.9 [1.3; 2.7] cases/1000 person-years. The risk of CKD was higher in patients with HBP (4.3[1.8;9.9], p = 0.001), 40-49 yr. patients (4.2[1.6;11.2], p = 0.004), ≥50 yr. patients (4.5[1.5;14.1], p = 0.009) and patients exposed to abacavir (ABC) or didanosine (ddI) based ART (13.1[4.0;42.9], p < 0.001).ConclusionsOur findings do not confirm the high risk of CKD reported in previous studies of West Africans with HIV, but support the recommendations for early initiation of ART and close kidney function monitoring in patients with HBP or aged ≥40 yr.

Multiplex Real-time PCR Detection of Intestinal Protozoa in HIV-infected Children in Malawi: Enterocytozoon Bieneusi Is Common and Associated With Gastrointestinal Complaints and May Delay BMI (Nutritional Status) Recovery.

Intestinal protozoa are common opportunistic infections in HIV patients. Longitudinal studies on either the clinical relevance or the effect of immune reconstitution by antiretroviral therapy on intestinal protozoan infections in children are lacking however. This study investigates prevalence and clinical relevance of intestinal protozoa in HIV-infected Malawian children before and during their first year of antiretroviral treatment (ART). Stool samples collected at enrolment and during follow-up were tested for nonopportunistic (Giardia lamblia, Dientamoeba fragilis, Entamoeba histolytica) and opportunistic protozoa (Enterocytozoon bieneusi, Encephalitozoon spp., Cryptosporidium spp. and Cystoisospora belli) using multiplex real-time polymerase chain reaction. Associations between infections and clinical symptoms were evaluated using univariate methods. Nonopportunistic and opportunistic protozoa were detected in 40% (14/35) and 46% (16/35) of children at baseline, respectively. E. bieneusi was the most prevalent protozoa (37%, 13/35) and associated with gastrointestinal complaints (43% in positive (10/13) versus 18% (4/22) in E. bieneusi-negative children, P = 0.001. Body mass index recovery during 12 months of ART was more commonly delayed in E. bieneusi-positive children (+0.29 +standard deviation 0.83) than E. bieneusi-negative children (+1.03 +standard deviation 1.25; P = 0.05). E. bieneusi was not detected after 12 months of ART. E. bieneusi was the most prevalent opportunistic intestinal protozoa, present in over a third of study participants before initiation of ART. Although all children cleared E. bieneusi after 12 months of ART, E. bieneusi was associated with gastrointestinal complaints and may delay body mass index recovery. Trials to assess effect of treatment of E. bieneusi on nutritional status should be considered in HIV-infected African children.

PS-082 Causes for discontinuing antiretroviral treatment within the first year in PSITAR HIV cohort

BackgroundTreatment modifications during the first year of starting antiretroviral treatment (ART) are extremely important. The first ART regimen should remain for years. First regimen toxicity can have a negative impact...

Hepatitis B and C Co-Infection among HIV-Infected Adults while on Antiretroviral Treatment: Long-Term Survival, CD4 Cell Count Recovery and Antiretroviral Toxicity in Cambodia

BackgroundDespite the high burden, there is a dearth of (long-term) outcome data of hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infected patients receiving antiretroviral treatment (ART) in a clinical setting in resource-constrained settings, particularly from Asia.MethodsWe conducted a retrospective cohort study including all adults initiating standard ART (non-tenofovir-based) between 03/2003 and 09/2012. HBV infection was diagnosed by HBV surface antigen detection. HCV diagnosis relied on antibody detection. The independent effect of HBV and HCV on long-term (≥5 years) ART response in terms of mortality (using Cox regression), severe livertoxicity (using logistic regression) and CD4 count increase (using mixed-effects modelling) was determined.ResultsA total of 3089 adults were included (median age: 35 years (interquartile range 30–41); 46% male), of whom 341 (11.0%) were co-infected with HBV and 163 (5.3%) with HCV. Over a median ART follow-up time of 4.3 years, 240 individuals died. Mortality was 1.6 higher for HBV co-infection in adjusted analysis (P = 0.010). After the first year of ART, the independent mortality risk was 3-fold increased in HCV co-infection (P = 0.002). A total of 180 (5.8%) individuals discontinued efavirenz or nevirapine due to severe livertoxicity, with an independently increased risk for HBV (hazard ratio (HR) 2.3; P<0.001) and HCV (HR 2.8; P<0.001). CD4 recovery was lower in both HBV and HCV co-infection but only statistically significant for HBV (P<0.001).DiscussionHBV and HCV co-infection was associated with worse ART outcomes. The effect of early ART initiation and providing effective treatment for hepatitis co-infection should be explored.

Prevalent and Incident Tuberculosis Are Independent Risk Factors for Mortality among Patients Accessing Antiretroviral Therapy in South Africa

BackgroundPatients with prevalent or incident tuberculosis (TB) in antiretroviral treatment (ART) programmes in sub-Saharan Africa have high mortality risk. However, published data are contradictory as to whether TB is a risk factor for mortality that is independent of CD4 cell counts and other patient characteristics.Methods/FindingsThis observational ART cohort study was based in Cape Town, South Africa. Deaths from all causes were ascertained among patients receiving ART for up to 8 years. TB diagnoses and 4-monthly CD4 cell counts were recorded. Mortality rates were calculated and Poisson regression models were used to calculate incidence rate ratios (IRR) and identify risk factors for mortality. Of 1544 patients starting ART, 464 patients had prevalent TB at baseline and 424 developed incident TB during a median of 5.0 years follow-up. Most TB diagnoses (73.6%) were culture-confirmed. A total of 208 (13.5%) patients died during ART and mortality rates were 8.84 deaths/100 person-years during the first year of ART and decreased to 1.14 deaths/100 person-years after 5 years. In multivariate analyses adjusted for baseline and time-updated risk factors, both prevalent and incident TB were independent risk factors for mortality (IRR 1.7 [95% CI, 1.2–2.3] and 2.7 [95% CI, 1.9–3.8], respectively). Adjusted mortality risks were higher in the first 6 months of ART for those with prevalent TB at baseline (IRR 2.33; 95% CI, 1.5–3.5) and within the 6 months following diagnoses of incident TB (IRR 3.8; 95% CI, 2.6–5.7).ConclusionsPrevalent TB at baseline and incident TB during ART were strongly associated with increased mortality risk. This effect was time-dependent, suggesting that TB and mortality are likely to be causally related and that TB is not simply an epiphenomenon among highly immunocompromised patients. Strategies to rapidly diagnose, treat and prevent TB prior to and during ART urgently need to be implemented.

Tuberculosis and the risk of opportunistic infections and cancers in HIV‐infected patients starting ART in Southern Africa

To investigate the incidence of selected opportunistic infections (OIs) and cancers and the role of a history of tuberculosis (TB) as a risk factor for developing these conditions in HIV-infected patients starting antiretroviral treatment (ART) in Southern Africa. Five ART programmes from Zimbabwe, Zambia and South Africa participated. Outcomes were extrapulmonary cryptococcal disease (CM), pneumonia due to Pneumocystis jirovecii (PCP), Kaposi's sarcoma and Non-Hodgkin lymphoma. A history of TB was defined as a TB diagnosis before or at the start of ART. We used Cox models adjusted for age, sex, CD4 cell count at ART start and treatment site, presenting results as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). We analysed data from 175,212 patients enrolled between 2000 and 2010 and identified 702 patients with incident CM (including 205 with a TB history) and 487 with incident PCP (including 179 with a TB history). The incidence per 100 person-years over the first year of ART was 0.48 (95% CI 0.44-0.52) for CM, 0.35 (95% CI 0.32-0.38) for PCP, 0.31 (95% CI 0.29-0.35) for Kaposi's sarcoma and 0.02 (95% CI 0.01-0.03) for Non-Hodgkin lymphoma. A history of TB was associated with cryptococcal disease (aHR 1.28, 95% CI 1.05-1.55) and Pneumocystis jirovecii pneumonia (aHR 1.61, 95% CI 1.27-2.04), but not with Non-Hodgkin lymphoma (aHR 1.09, 95% CI 0.45-2.65) or Kaposi's sarcoma (aHR 1.02, 95% CI 0.81-1.27). Our study suggests that there may be interactions between different OIs in HIV-infected patients.

Mortality and loss to follow-up in the first year of ART

To analyse mortality, loss to follow-up (LTFU) and retention on antiretroviral treatment (ART) in the first year of ART across all age groups in the Malawi national ART programme. Cohort study including all patients who started ART in Malawi's public sector clinics between 2004 and 2007. ART registers were photographed, information entered into a database and merged with data from clinics with electronic records. Rates per 100 patient-years and cumulative incidence of retention were calculated. Subhazard ratios (sHRs) of outcomes adjusted for patient and clinic-level characteristics were calculated in multivariable analysis, applying competing risk models. A total of 117,945 patients contributed 85,246 person-years: 1.0% were infants below 2 years, 7.4% children 2-14, 7.5% young people 15-24, and 84.2% adults 25 years and above. Sixty percent of patients were female: women outnumbered men from age 14 to 35 years. Mortality and LTFU were higher in men from age 20 years. Infants and young people had the highest rates per 100 person-years for mortality (23.0 and 19.4) and LTFU (24.7 and 19.3), and the highest adjusted relative risks compared to age group 25-34 years: sHRs were 1.37 [95% confidence interval (CI) 1.17-1.60] and 1.17 (95% CI 1.10-1.25) for death and 1.37 (95% CI 1.18-1.59) and 1.27 (95% CI 1.19-1.35) for LTFU, respectively. In this country-wide study patients aged 0-1 and 15-24 years had the highest risk of death and LTFU, and from age 20 men were at higher risk than women. Interventions to improve outcomes in these patient groups are required.

Sub-Optimal CD4 T-Lymphocyte Responses among HIV Infected Patients who Develop TB during the First Year of ART

STUDY BACKGROUND: Poor CD4 T-lymphocyte responses to anti-retroviral treatment (ART) are associated with increased HIV disease progression and mortality. In sub-Saharan Africa a substantial proportion of HIV infected patients are co-infected with TB. This study evaluated the effect of active TB presenting after ART initiation on immunological responses to ART. METHODS: A retrospective cohort study was conducted of patients initiated on ART in a South African academic hospital between 1 January 2004 and 15 May 2008. Changes in CD4 T-lymphocyte count, virological suppression and incident TB episodes occurring in the first year of ART were assessed. Sub-optimal CD4 responses were defined as 'failure to increase CD4 T-lymphocyte count by 50cells/μl at 6 month on ART'. RESULTS: The cohort for analysis included 691 patients. 141 (20.4%) had sub-optimal CD4 responses at 6 months on ART. 49 patients (7.1%) developed incident TB within the first 12 months of ART. After adjustment for age, sex, baseline CD4 count and detectable viral load, patients with incident TB were found to have a 2.20 times greater odds of a sub-optimal CD4 response at 6 month of ART as compared to those who were TB free (95%CI: 1.14-4.23). CONCLUSION: Incident TB was associated with a poor CD4 response during early ART in this cohort. Although the direction of causality cannot be determined from these data, these findings provide additional support for the initiation of ART at higher CD4 counts.

Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa.

BackgroundEvaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up.Methods and FindingsTreatment-naïve patients starting combination ART in five programmes in Côte d'Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9–6.5%) to 10.9% (9.6–12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9–11.6%) to 16.9% (15.0–19.1%), with relative increases in mortality ranging from 27% to 73% across programmes.ConclusionsNaïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.

Weight loss after the first year of stavudine-containing antiretroviral therapy and its association with lipoatrophy, virological failure, adherence and CD4 counts at primary health care level in Kigali, Rwanda

This study was conducted among 609 adults on stavudine-based antiretroviral treatment (ART) for at least one year at health center level in Kigali, Rwanda to (a) determine the proportion who manifest weight loss after one year of ART (b) examine the association between such weight loss and a number of variables, namely: lipoatrophy, virological failure, adherence and on-treatment CD4 count and (c) assess the validity and predictive values of weight loss to identify patients with lipoatrophy. Weight loss after the first year of ART was seen in 62% of all patients (median weight loss 3.1 kg/year). In multivariate analysis, weight loss was significantly associated with treatment-limiting lipoatrophy (adjusted effect/kg/year -2.0 kg, 95% confidence interval -0.6;-3.4 kg; P<0.01). No significant association was found with virological failure or adherence. Higher on-treatment CD4 cell counts were protective against weight loss. Weight loss that was persistent, progressive and/or chronic was predictive of lipoatrophy, with a sensitivity and specificity of 72% and 77%, and positive and negative predictive values of 30% and 95%. In low-income countries, measuring weight is a routine clinical procedure that could be used to filter out individuals with lipoatrophy on stavudine-based ART, after alternative causes of weight loss have been ruled out.

Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa

Two-thirds of the world's HIV-infected people live in sub-Saharan Africa, and more than 1.5 million of them die annually. As access to antiretroviral treatment has expanded within the region; early pessimism concerning the delivery of antiretroviral treatment using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to ART are similar to responses in patients treated in high-income countries. Despite this, however, early mortality rates in sub-Saharan Africa are very high; between 8 and 26% of patients die in the first year of antiretroviral treatment, with most deaths occurring in the first few months. Patients typically access antiretroviral treatment with advanced symptomatic disease, and mortality is strongly associated with baseline CD4 cell count less than 50 cells/mul and WHO stage 4 disease (AIDS). Although data are limited, leading causes of death appear to be tuberculosis, acute sepsis, cryptococcal meningitis, malignancy and wasting syndrome. Mortality rates are likely to depend not only on the care delivered by antiretroviral treatment programmes, but more fundamentally on how advanced disease is at programme enrollment and the quality of preceding healthcare. In addition to improving delivery of antiretroviral treatment and providing it free of charge to the patient, strategies to reduce mortality must include earlier diagnosis of HIV infection, strengthening of longitudinal HIV care and timely initiation of antiretroviral treatment. Health systems delays in antiretroviral treatment initiation must be minimized, especially in patients who present with advanced immunodeficiency.