Loss to programme between HIV diagnosis and initiation of antiretroviral therapy in sub‐Saharan Africa: systematic review and meta‐analysis

Objectives To assess the proportion of patients lost to programme (died, lost to follow‐up, transferred out) between HIV diagnosis and start of antiretroviral therapy (ART) in sub‐Saharan Africa, and determine factors associated with loss to programme. Methods Systematic review and meta‐analysis. We searched PubMed and EMBASE databases for studies in adults. Outcomes were the percentage of patients dying before starting ART, the percentage lost to follow‐up, the percentage with a CD4 cell count, the distribution of first CD4 counts and the percentage of eligible patients starting ART. Data were combined using random‐effects meta‐analysis. Results Twenty‐nine studies from sub‐Saharan Africa including 148 912 patients were analysed. Six studies covered the whole period from HIV diagnosis to ART start. Meta‐analysis of these studies showed that of the 100 patients with a positive HIV test, 72 (95% CI 60–84) had a CD4 cell count measured, 40 (95% CI 26–55) were eligible for ART and 25 (95% CI 13–37) started ART. There was substantial heterogeneity between studies (P < 0.0001). Median CD4 cell count at presentation ranged from 154 to 274 cells/μl. Patients eligible for ART were less likely to become lost to programme (25%vs. 54%, P < 0.0001), but eligible patients were more likely to die (11%vs. 5%, P < 0.0001) than ineligible patients. Loss to programme was higher in men, in patients with low CD4 cell counts and low socio‐economic status and in recent time periods. Conclusions Monitoring and care in the pre‐ART time period need improvement, with greater emphasis on patients not yet eligible for ART.     

Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study

Objectives

To investigate delayed HIV diagnosis and late initiation of antiretroviral therapy (ART) in the Swiss HIV Cohort Study.

Methods

Two sub‐populations were included: 1915 patients with HIV diagnosis from 1998 to 2007 and within 3 months of cohort registration (group A), and 1730 treatment‐naïve patients with CD4≥200 cells/μL before their second cohort visit (group B). In group A, predictors for low initial CD4 cell counts were examined with a median regression. In group B, we studied predictors for CD4<200 cells/μL without ART despite cohort follow‐up.

Results

Median initial CD4 cell count in group A was 331 cells/μL; 31% and 10% were <200 and <50 cells/μL, respectively. Risk factors for low CD4 count were age and non‐White race. Homosexual transmission, intravenous drug use and living alone were protective. In group B, 30% initiated ART with CD4≥200 cells/μL; 18% and 2% dropped to CD4 <200 and <50 cells/μL without ART, respectively. Sub‐Saharan origin was associated with lower probability of CD4 <200 cells/μL without ART during follow‐up. Median CD4 count at ART initiation was 207 and 253 cells/μL in groups A and B, respectively.

Conclusions

CD4<200 cells/μL and, particularly, CD4<50 cells/μL before starting ART are predominantly caused by late presentation. Earlier HIV diagnosis is paramount.     

Cost of medical care for HIV-infected patients within a regional population from 1997 to 2006

Objectives

To report on the cost of medical care for HIV‐infected patients stratified by CD4 cell count for a regional population over a 9‐year period, and to examine the effect of reporting costs of HIV care only or only in antiretroviral therapy (ART)‐experienced patients.

Methods

Retrospective costing analysis on all HIV‐infected patients within the Southern Alberta Cohort from April 1997 to April 2006. Costs for all drugs (ART/non‐ART), in‐patient (HIV/non‐HIV) and out‐patient care were obtained from primary sources. Costs were aggregated by patient's CD4 cell count and ART exposure and presented as mean cost per patient per month (PPPM) in 2006 Canadian dollars.

Results

The number of patients and annual costs increased by 74% and 69%, respectively. Overall mean PPPM costs increased slightly from $1082 in 1997/1998 to $1159 in 2005/2006. PPPM costs for patients with CD4 counts ≤75 cells/μL increased from $1595 to $2687 while costs for CD4 counts >500, 201–500 and 76–200 cells/μL remained relatively stable at $979, $1057 and $1294, respectively. In‐patient hospitalization costs account for most of the cost increases. Reporting costs using only ART‐experienced patients would overestimate total costs by 2–9%. Costs for only HIV care were 10–24% lower than total care costs.

Conclusions

Care costs have remained relatively stable for most HIV patients except those with CD4 counts ≤75 cells/μL. Expensive new antiretroviral drugs have had, at present, a minimal cost impact. Enhanced testing to achieve earlier diagnosis and initiation of highly active antiretroviral therapy could potentially reduce costs of late presentation and in‐patient care.     

Standard-dose efavirenz vs. standard-dose nevirapine in antiretroviral regimens among HIV-1 and tuberculosis co-infected patients who received rifampicin

Background

There is limited comparative data between efavirenz (EFV) 600 mg/day and nevirapine (NVP) 400 mg/day‐based antiretroviral therapy (ART) among HIV‐1 patients with tuberculosis (TB) and receiving rifampicin.

Methods

A retrospective cohort study was conducted in all ART‐naïve patients who were receiving rifampicin between January 2002 and December 2005.

Results

Of 188 patients, 77 and 111 patients were initiated on EFV‐based ART (EFV group) and NVP‐based ART (NVP group), respectively. Overall, median [interquartile range (IQR)] CD4 count was 36 (15–77) cells/μL and median (IQR) viral load was 5.6 (5.2–5.9) HIV‐1 RNA log copies/mL. At 48 weeks, 77.9% (60/77) in the EFV group and 67.6% (75/111) in the NVP group achieved HIV‐1 RNA <50 copies/mL (P=0.140, odds ratio =0.590, 95% confidence interval=0.302–1.153). At 24 and 48 weeks, respective median CD4 counts were 174 and 254 cells/μL in the EFV group and 156 and 218 cells/μL in the NVP group (P>0.05). By binary logistic regression, treatment group was not associated with HIV‐1 RNA <50 copies/mL (P>0.05). No patient in the EFV group and eight (7.2%) patients in the NVP group discontinued ART because of adverse reactions (P=0.084).

Conclusions

For HIV–TB co‐infected patients who receive rifampicin, efficacy of 600 mg EFV‐based and 400 mg NVP‐based ART may be similar, although adverse events tend to be higher in NVP‐based ART.     

High prevalence of distal sensory polyneuropathy in antiretroviral-treated and untreated people with HIV in Tanzania

Objectives To describe the prevalence of distal sensory polyneuropathy (DSP), a complication of both advanced HIV disease and of antiretroviral therapy (ART), amongst Tanzanians with HIV, on and off ART (including stavudine) with CD4 counts above and below 200 cells/μl. Methods We recruited participants attending ART clinic into four groups: >6 months ART exposure and (i) CD4 < 200 cells/μl or (ii) CD4 > 200 cells/μl (ART/CD4 < 200 and ART/CD4 > 200, respectively); ART‐naïve and (iii) CD4 < 200 cells/μl or iv)CD4 > 200 cells/μl (noART/CD4 < 200 and noART/CD4 > 200, respectively). Primary outcome was DSP, as defined by presence of at least one symptom and one sign. Results Of 326 evaluable participants, 81 (32 men, median age 38 years, median CD4 142 cells/μl) were enrolled in the ART/CD4 < 200 group, 78 (17 men, median age 37 years, median CD4 345 cells/μl) in ART/CD4 > 200, 81 (30 men, median age 37 years, median CD4 128 cells/μl) in noART/CD4 < 200 and 86 (22 men, median age 33 years, median CD4 446 cells/μl) in noART/CD4 > 200. Numbness was the most commonly reported symptom. DSP prevalence ranged from 43.2% in ART/CD4 < 200 to 20.9% in noART/CD4 > 200. DSP was more common among men (adjusted odds ratio [aOR] 1.9, 95% confidence interval [CI] 1.2–3.3) and older participants (aOR 2.7, 95% CI 1.1–6.2 for age 40 + vs. <30 years). Conclusion Distal sensory polyneuropathy is common amongst those attending this clinic, even those with no ART exposure and a CD4 count above 200 cells/μl. Stavudine and didanosine expose HIV‐infected patients to an additional avoidable risk of DSP. Access to non‐neurotoxic ART regimes as well as earlier HIV diagnosis and initiation of ART is needed.     

Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa

OBJECTIVE: To determine the burden and impact of immune reconstitution disease (IRD) associated with tuberculosis (TB) among patients initiating antiretroviral treatment (ART) in sub-Saharan Africa. DESIGN: Retrospective analysis of a study cohort enrolled over 3 years within a community-based ART service in South Africa. METHODS: Patients receiving treatment for TB at the time ART was initiated (n = 160) were studied. Cases of TB-associated IRD during the first 4 months of ART were ascertained. RESULTS: The median baseline CD4 cell count was 68 cells/microl [interquartile range (IQR), 29-133 cells/microl) and ART was initiated after a median of 105 days (IQR, 61-164 days) from TB diagnosis. Although IRD was diagnosed in just 12% (n = 19) of patients overall, IRD developed in 32% (n = 12) of those who started ART within 2 months of TB diagnosis. Pulmonary involvement was observed in 84% (n = 16) and intra-abdominal manifestations were also common (37%). Overall, 4% (n = 7) of the cohort required secondary level health-care for IRD and two (1%) patients died. In multivariate analysis, risk of IRD was strongly associated with early ART initiation and low baseline CD4 cell count. Of patients with CD4 counts < 50 cells/microl, the proportions who developed IRD following initiation of ART within 0-30, 31-60, 61-90, 91-120 and > 120 days of TB diagnosis were 100%, 33%, 14%, 7% and 0%, respectively. CONCLUSIONS: The risk of TB-associated IRD in this setting is very high for those with low baseline CD4 cell counts initiating ART early in the course of antituberculosis treatment. However, most cases were self-limiting; overall secondary health-care utilization and mortality risk from IRD were low.     

Participation, characteristics and retention rates of HIV-positive immigrants in the Swiss HIV Cohort Study

Objective

Data from observational cohorts may be influenced by population structure and loss to follow‐up (LTFU). Quality of care may be associated with participation in cohort networks. We aimed to study the participation, characteristics and retention rates of immigrants in the Swiss HIV Cohort Study (SHCS).

Methods

We compared enrolment over time (1996–1999, 2000–2003 and 2004–2008) and LTFU between individuals from different geographical regions. In 2008, we performed a cross‐sectional survey to investigate the proportion of individuals not participating in the SHCS but who were in care at SHCS institutions. Predictors for LTFU were analysed using Cox proportional hazard models, and those for nonparticipation using logistic regression.

Results

A total of 7840 individuals entered the SHCS during the observation period. The proportion of immigrants increased over time, especially the proportion of women from sub‐Saharan Africa, which increased from 21 to 48% during the observation period. Overall LTFU was 3.76 [95% confidence interval (CI) 3.58–3.95]/100, with the highest hazard ratio in men from sub‐Saharan Africa (2.82/100 patient‐years; 95% CI 2.30–3.46/100), compared with men from northwestern countries. Other predictors for LTFU were age <30 years, lower education, injecting drug use, and higher baseline CD4 cell counts. Participants taking antiretroviral therapy had reduced LTFU. The survey showed that 84% of HIV‐infected patients in care at SHCS institutions were enrolled in the cohort. Nonparticipation was more likely among men from non‐European regions (odds ratio 2.73; 95% CI 2.29–3.24), women from sub‐Saharan Africa (odds ratio 3.01; 95% CI 2.40–3.77) and women from Latin America/Caribbean (odds ratio 2.10; 95% CI 1.30–3.39).

Conclusions

Numbers of HIV‐infected immigrants are increasing but they are underrepresented in the SHCS, and immigrants are more likely to be lost to follow‐up.     

Ensuring HIV‐infected pregnant women start antiretroviral treatment: an operational cohort study from Lilongwe,Malawi

Objectives HIV‐infected women identified through antenatal care (ANC) often fail to access antiretroviral treatment (ART), leaving them and their infants at risk for declining health or HIV transmission. We describe results of measures to improve uptake of ART among eligible pregnant women. Methods Between October 2006 and December 2009, interventions implemented at ANC and ART facilities in urban Lilongwe aimed to better link services for women with CD4 counts <250/μl. A monitoring system followed women referred for ART to examine trends and improve practices in referral completion, on‐time ART initiation and ART retention. Results Six hundred and twelve women were ART eligible: 604 (99%) received their CD4 result, 344 (56%) reached the clinic, 286 (47%) started ART while pregnant and 261 (43%) were either alive on ART or transferred out after 6 months. Between 2006 and 2009, the median (IQR) time between CD4 blood draw and ART initiation fell from 41 days (17, 349) to 15 days (7,42) (P = 0.183); the proportion of eligible individuals starting ART while pregnant and retained for 6 months improved from 17% to 65% (P < 0.001). Delays generally shortened within the continuum of care from 2006 to 2009; however, time from CD4 blood draw to ART referral increased from 7 to 14 days. Conclusions Referrals between facilities and delays through CD4 count measurements create bottlenecks in patient care. Retention improved over time, but delays within the linkage process remained. ART initiation at ANC plus use of point‐of‐care CD4 tests may further enhance ART uptake.     

Evaluation of affordable screening markers to detect CD4+ T‐cell counts below 200 cells/μl among HIV‐1‐infected Ugandan adults

Objective To evaluate validity of WHO staging, low body mass index (BMI) and anaemia in detecting HIV‐infected adults with CD4+ T‐cell counts < 200 cells/μl. Methods Between October 1995 and April 2006, we screened Ugandans aged 16 or older at enrolment into an open cohort. We analysed highly active anti‐retroviral therapy (HAART)‐naïve HIV‐infected patients with WHO stages 1–3 and complete data in a secondary cross‐sectional study. Low BMI was a BMI < 18.5 kg/m². Anaemia was a haemoglobin level < 11 or 12 g/dl among women and men respectively. Results Among 2892 HAART‐naïve patients, the median age was 32 years. 71% were women, 54% had WHO stage 3 AIDS, 34% had anaemia, 16% had a low BMI and 43% had CD4+ T‐cell counts < 200 cells/μl. WHO stage 3 compared to combined WHO stages 1 and 2 had a sensitivity (95% CI) of 70% (67, 72) and a specificity of 57% (55, 60) respectively to detect CD4+ T‐cell counts < 200 cells/μl. Anaemia compared to normal haemoglobin had sensitivity (95% CI) of 47% (44, 50) and a specificity of 76% (74, 78). Low BMI compared to normal BMI had sensitivity (95% CI) of 23% (20, 25) and a specificity of 89% (87, 90) against CD4+ T‐cell counts < 200 cells/μl. Conclusion Only WHO stage 3 had reasonably high sensitivity in detecting CD4+ T‐cell counts below 200 cells/μl in this setting. Targeted low‐cost CD4 testing strategies are urgently needed to detect patients eligible for HAART in rural Africa and other resource‐limited settings.     

Vertically acquired HIV diagnosed in adolescence and early adulthood in the United Kingdom and Ireland: findings from national surveillance

Objective

The aim of the study was to describe the characteristics of young people with vertically acquired HIV diagnosed aged ≥13 years.

Methods

A retrospective review of HIV diagnoses reported to well‐established national paediatric and adult HIV surveillance systems in the United Kingdom/Ireland was conducted.

Results

Forty‐two young people with vertically acquired HIV diagnosed aged ≥13 years were identified; 23 (55%) were female, 40 (95%) were black African and 36 (86%) were born in sub‐Saharan Africa. The median age at HIV diagnosis was 14 years (range, 13–20 years). Half of the patients presented with symptoms; the remainder were screened for HIV following diagnosis of a relative. The median CD4 count at diagnosis was 210 cells/μL (range, 0–689 cells/μL), 12 patients (29%) were diagnosed with AIDS at HIV diagnosis or subsequently, and 34 (81%) started combination antiretroviral therapy (ART), most (31 of 34) within a year of diagnosis.

Conclusion

A small number of young people with vertically acquired HIV survive childhood without ART and are diagnosed at age ≥13 years in the United Kingdom/Ireland. Half of the patients were asymptomatic, highlighting the importance of considering HIV testing for all offspring of HIV‐infected women, regardless of age or symptoms. Increased awareness among clinicians and parents is required to reduce delayed presentation with advanced disease and to avoid onward transmission as these young people become sexually active.     

Total lymphocyte count is a good marker for HIV-related mortality and can be used as a tool for starting HIV treatment in a resource-limited setting

Objectives Total lymphocyte counts (TLC) may be used as an alternative for CD4 cell counts to monitor HIV infection in resource‐limited settings, where CD4 cell counts are too expensive or not available. Methods We used prospectively collected patient data from an urban HIV clinic in Indonesia. Predictors of mortality were identified via Cox regression, and the relation between TLC and CD4 cell counts was calculated by linear regression. Receiver operating characteristics (ROC) curves were used to choose the cut‐off values of TLC corresponding with CD4 cell counts <200 and ≤350 cells/μl. Based on these analyses, we designed TLC‐based treatment algorithms. Results Of 889 antiretroviral treatment (ART)‐naïve subjects included, 66% had CD4 cell counts <200 and 81% had 350 ≤ cells/μl at baseline. TLC and CD4 cell count were equally strong predictors of mortality in our population, where ART was started based on CD4 cell count criteria. The correlation coefficient (R) between TLC and √CD4 was 0.70. Optimal cut‐off values for TLC to identify patients with CD4 cell counts <200 and ≤350 cells/μl were 1500 and 1700 cells/μl, respectively. Treatment algorithms based on a combination of TLC, gender, oral thrush, anaemia and body mass index performed better in terms of predictive value than WHO staging or TLC alone. In our cohort, such an algorithm would on average have saved $14.05 per patient. Conclusion Total lymphocyte counts is a good marker for HIV‐associated mortality. Simple algorithms including TLC can prioritize patients for HIV treatment in a resource‐limited setting, until affordable CD4 cell counts will be universally available.     

Use of nail and oral pigmentation to determine ART eligibility among HIV‐infected Ugandan adults

Objectives To evaluate the use of grey/distal banded nails as an indicator of advanced immunosuppression, and thus eligibility for ART, in resource poor settings. Methods We tested whether grey/distal banded nails and/or oral pigmentation could be used to identify patients with low CD4 cell counts at two cut‐offs: <200 and <350 cells/μl in ART naive adults. Results Four hundred and three nail and oral cavities were photographed and assessed. Grey/distal banded nails and/or oral pigmentation were significantly associated with a CD4 cell count <200 cells/μl (P < 0.001), with a sensitivity of 66%, a specificity of 50% and a negative predictive value of 77%. However, there was no association when a CD4 cell count cut‐off of <350 cells/μl was used. Inter‐observer agreement (k 0.46) was fair/moderate. Conclusions While grey/distal banded nails and/or oral pigmentation are associated with low CD4 counts, the sensitivity and kappa score are too low for this method to be recommended as a tool to guide ART initiation; large number of individuals eligible for ART would be missed.     

HIV status and participation in HIV surveillance in the era of antiretroviral treatment: a study of linked population‐based and clinical data in rural South Africa

Objective To examine whether HIV status affects participation in a population‐based longitudinal HIV surveillance in the context of an expanding HIV treatment and care programme in rural South Africa. Method We regressed consent to participate in the HIV surveillance during the most recent fieldworker visit on HIV status (based on previous surveillance participation or enrolment in pre‐antiretroviral treatment (pre‐ART) care or ART in the local HIV treatment and care programme), controlling for sex, age and year of the visit (N = 25 940). We then repeated the regression using the same sample but, in one model, stratifying HIV‐infected persons into three groups (neither enrolled in pre‐ART care nor receiving ART; enrolled in pre‐ART care but not receiving ART; receiving ART) and, in another model, additionally stratifying the group enrolled in pre‐ART and the group receiving ART into those with CD4 count ≤200/μl (i.e. the ART eligibility threshold at the time) vs. those with CD4 count >200/μl. Results HIV‐infected individuals were significantly less likely to consent to participate in the surveillance than HIV‐uninfected individuals [adjusted odds ratio (aOR), 0.74; 95% confidence interval, 0.70–0.79, P < 0.001], controlling for other factors. Persons who were receiving ART were less likely to consent to participate (aOR, 0.75, 0.68–0.84, P < 0.001) than those who had never sought HIV treatment or care (aOR, 0.82, 0.75–0.89, P < 0.001), but more likely to consent than persons enrolled in pre‐ART care (aOR 0.62, 0.56–0.69, P < 0.001). Those with CD4 count ≤200/μl were significantly less likely to consent to participate than those with CD4 count >200/μl in both the group enrolled in pre‐ART and the group receiving ART. Conclusion As HIV test results are not made available to participants in the HIV surveillance, our findings agree with the hypothesis that HIV‐infected persons are less likely than HIV‐uninfected persons to participate in HIV surveillance because they fear the negative consequences of others learning about their HIV infection. Our results further suggest that the increased knowledge of HIV status that accompanies improved ART access can reduce surveillance participation of HIV‐infected persons, but that this effect decreases after ART initiation, in particular in successfully treated patients.     

Criteria for initiating highly active antiretroviral therapy and short-term immune response among HIV-1-infected patients in Côte d'Ivoire

Objectives

The aims of this study were to determine the predictors of CD4 count below 200 cells/μL and to propose an algorithm for antiretroviral therapy initiation; and to assess the determinants of immune response to highly active antiretroviral therapy (HAART) in Côte d'Ivoire.

Methods

A total of 615 consecutive patients attending an HIV/AIDS day hospital were enrolled in the study. We constructed a score system based on the results of a multivariate logistic regression analysis of the predictors of CD4 count <200 cells/μL with the intention of proposing an algorithm able to accurately designate patients eligible for HAART. We also identified factors associated with a short‐term increase in CD4 count >50 cells/μL after HAART initiation.

Results

Total lymphocyte count <1200 cells/μL (P<0.0001), lower haemoglobin levels (P<0.0001), and Centers for Disease Control and Prevention (CDC) clinical stages C (P=0.005) and B (P=0.045), as compared with stage A, were associated with CD4 count <200 cells/μL. Nonetheless, no accurate algorithm for HAART initiation was found. Three hundred and three of the 615 patients were treated. Of these 303 patients, 79.5% showed an increase of >50 cells/μL in CD4 count 6 months after HAART initiation (median increase 128 cells/μL). Adherence ≥95% (P=0.022) and increase in absolute total lymphocyte count during follow‐up (P<0.0001) were associated with a short‐term positive immune response.

Conclusions

Our results support the effectiveness of generic drug combinations in sub‐Saharan Africa. In order to enhance the management of HIV disease in sub‐Saharan Africa, efforts should target the development of low‐cost CD4 cell count laboratory tests.     

Practices to improve identification of adult antiretroviral therapy failure at the Lighthouse Trust clinic in Lilongwe, Malawi

Objectives Evaluating treatment failure is critical when deciding to modify antiretroviral therapy (ART). Virologic Assessment Forms (VAFs) were implemented in July 2008 as a prerequisite for ordering viral load. The form requires assessment of clinical and immunologic status. Methods Using the Electronic Medical Record (EMR), we retrospectively evaluated patients who met 2006 WHO guidelines for immunologic failure (≥15 years old; on ART ≥6 months; CD4 count 50% drop from peak OR CD4 persistently <100 cells) at the Lighthouse Trust clinic from December 2007 to December 2009. We compared virologic screening, VAF implementation and ART modification during the same period using Fisher’s exact tests and unpaired t‐tests as appropriate. Results Of 7000 enrolled ART patients ≥15 years old with at least two CD4 counts, 10% had immunologic failure with a median follow‐up time on ART of 1.4 years (IQR: 0.8–2.3). Forty (6%) viral loads were ordered: 14 (35%) were detectable (>400 HIV RNA copies/mL) and one (7%) patient was switched to second‐line therapy. Overall, 259 VAFs were completed: 67% for immunologic failure and 33% for WHO Stage 4 condition. Before VAF implementation, 1% of patients had viral loads drawn during routine care, whereas afterwards, 8% did (P < 0.0001; 95% CI: 0.03–0.08). Conclusions Clinicians did not identify a large proportion of immunologic failure patients for screening. Implementation of VAFs produced little improvement in virologic screening during routine care. Better training and monitoring systems are needed.     

Low mortality risk but high loss to follow‐up among patients in the Tanzanian national HIV care and treatment programme

Objective To analyse survival and retention rates of the Tanzanian care and treatment programme. Methods Routine patient‐level data were available from 101 of 909 clinics. Kaplan–Meier probabilities of mortality and attrition after ART initiation were calculated. Mortality risks were corrected for biases from loss to follow‐up using Egger’s nomogram. Smoothed hazard rates showed mortality and attrition peaks. Cox regression identified factors associated with death and attrition. Median CD4 counts were calculated at 6 month intervals. Results In 88,875 adults, 18% were lost to follow up 12 months after treatment initiation, and 36% after 36 months. Cumulative mortality reached 10% by 12 months (15% after correcting for loss to follow‐up) and 14% by 36 months. Mortality and attrition rates both peaked within the first six months, and were higher among males, those under 45 kg and those with CD4 counts below 50 cells/μl at ART initiation. In the first year on ART, median CD4 count increased by 126 cells/μl, with similar changes in both sexes. Conclusion Earlier diagnoses through expanded HIV testing may reduce high mortality and attrition rates if combined with better patient tracing systems. Further research is needed to explore reasons for attrition.     

Prevalence and burden of HBV co‐infection among people living with HIV: A global systematic review and meta‐analysis

Globally, in 2017 35 million people were living with HIV (PLHIV) and 257 million had chronic HBV infection (HBsAg positive). The extent of HIV‐HBsAg co‐infection is unknown. We undertook a systematic review to estimate the global burden of HBsAg co‐infection in PLHIV. We searched MEDLINE, Embase and other databases for published studies (2002‐2018) measuring prevalence of HBsAg among PLHIV. The review was registered with PROSPERO (#CRD42019123388). Populations were categorized by HIV‐exposure category. The global burden of co‐infection was estimated by applying regional co‐infection prevalence estimates to UNAIDS estimates of PLHIV. We conducted a meta‐analysis to estimate the odds of HBsAg among PLHIV compared to HIV‐negative individuals. We identified 506 estimates (475 studies) of HIV‐HBsAg co‐infection prevalence from 80/195 (41.0%) countries. Globally, the prevalence of HIV‐HBsAg co‐infection is 7.6% (IQR 5.6%‐12.1%) in PLHIV, or 2.7 million HIV‐HBsAg co‐infections (IQR 2.0‐4.2). The greatest burden (69% of cases; 1.9 million) is in sub‐Saharan Africa. Globally, there was little difference in prevalence of HIV‐HBsAg co‐infection by population group (approximately 6%‐7%), but it was slightly higher among people who inject drugs (11.8% IQR 6.0%‐16.9%). Odds of HBsAg infection were 1.4 times higher among PLHIV compared to HIV‐negative individuals. There is therefore, a high global burden of HIV‐HBsAg co‐infection, especially in sub‐Saharan Africa. Key prevention strategies include infant HBV vaccination, including a timely birth‐dose. Findings also highlight the importance of targeting PLHIV, especially high‐risk groups for testing, catch‐up HBV vaccination and other preventative interventions. The global scale‐up of antiretroviral therapy (ART) for PLHIV using a tenofovir‐based ART regimen provides an opportunity to simultaneously treat those with HBV co‐infection, and in pregnant women to also reduce mother‐to‐child transmission of HBV alongside HIV.     

Immunovirological outcomes and resistance patterns at 4 years of antiretroviral therapy use in HIV-infected patients in Cambodia

Objectives To report immunovirological outcomes and resistance patterns in adults treated with triple combination antiretroviral therapy (cART) for 4 years in an HIV programme of Phnom Penh, Cambodia. Methods It is a longitudinal study and cross‐sectional evaluation of adults receiving cART for 4 years. CD4 cell counts and HIV‐1 RNA were quantified, and resistance patterns were determined. Drug‐related toxicity was assessed by clinicians and through laboratory testing. Results After 4 years of cART start, the cumulative probability of retention in care was 0.80 and survival among patients not lost to follow‐up was 0.85. A total of 349 patients (98% of eligible) participated in the cross‐sectional evaluation. Ninety per cent were receiving first‐line therapy, 29% stavudine‐ and 58% zidovudine‐containing regimens (compared with 94% and 3% at cART initiation). Ninety‐three per cent of patients were clinically asymptomatic, and severe lipodystrophy and dyslipidemia were diagnosed in 7.2% and 4.0%, respectively. Good treatment adherence was reported by 83% of patients. Median CD4 T‐cell count was 410 cells/μl [IQR 290–511], and 90% of patients had >200 cells/μl. Only 15 (4%) patients had detectable HIV viral load (eight had <200 CD4 cells/μl), five had thymidine analogue mutations, and nine were resistant to two drug classes. In an intention‐to‐treat analysis, 26.1% (95% CI 22.0–30.5) of patients had failed first‐line therapy. Conclusions In this Cambodian cohort of adults who started cART at an advanced stage of HIV disease, we observed good clinical and immunovirological outcomes and self‐reported treatment adherence at 4 years of therapy.     

Adult mortality and probable cause of death in rural northern Malawi in the era of HIV treatment

Objectives Developing countries are undergoing demographic transition with a shift from high mortality caused by communicable diseases (CD) to lower mortality rates caused by non‐communicable diseases (NCD). HIV/AIDS has disrupted this trend in sub‐Saharan Africa. However, in recent years, HIV‐associated mortality has been reduced with the introduction of widely available antiretroviral therapy (ART). Side effects of ART may lead to increased risk of cardiovascular diseases, raising the prospects of an accelerated transition towards NCD as the primary cause of death. We report population‐based data to investigate changes in cause of death owing to NCD during the first 4 years after introduction of HIV treatment. Methods We analysed data from a demographic surveillance system in Karonga district, Malawi, from September 2004 to August 2009. ART was introduced in mid‐2005. Clinician review of verbal autopsies conducted 2–6 weeks after a death was used to establish a single principal cause of death. Results Over the entire period, there were 905 deaths, AIDS death rate fell from 505 to 160/100 000 person‐years, and there was no evidence of an increase in NCD rates. The proportion of total deaths attributable to AIDS fell from 42% to 17% and from NCD increased from 37% to 49%. Discussion Our findings show that 4 years after the introduction of ART into HIV care in Karonga district, all‐cause mortality has fallen dramatically, with no evidence of an increase in deaths owing to NCD.