Risk factors for pre-treatment mortality among HIV-infected children in rural Zambia: a cohort study

Background

Many HIV-infected children in sub-Saharan Africa enter care at a late stage of disease. As preparation of the child and family for antiretroviral therapy (ART) can take several clinic visits, some children die prior to ART initiation. This study was undertaken to determine mortality rates and clinical predictors of mortality during the period prior to ART initiation.

Methods

A prospective cohort study of HIV-infected treatment-naïve children was conducted between September 2007 and September 2010 at the HIV clinic at Macha Hospital in rural Southern Province, Zambia. HIV-infected children younger than 16 years of age who were treatment-naïve at study enrollment were eligible for analysis. Mortality rates prior to ART initiation were calculated and risk factors for mortality were evaluated.

Results

351 children were included in the study, of whom 210 (59.8%) were eligible for ART at study enrollment. Among children ineligible for ART at enrollment, 6 children died (mortality rate: 0.33; 95% CI:0.15, 0.74). Among children eligible at enrollment, 21 children died before initiation of ART and their mortality rate (2.73 per 100 person-years; 95% CI:1.78, 4.18) was significantly higher than among children ineligible for ART (incidence rate ratio: 8.20; 95% CI:3.20, 24.83). In both groups, mortality was highest in the first three months of follow-up. Factors associated with mortality included younger age, anemia and lower weight-for-age z-score at study enrollment.

Conclusions

These results underscore the need to increase efforts to identify HIV-infected children at an earlier age and stage of disease progression so they can enroll in HIV care and treatment programs prior to becoming eligible for ART and these deaths can be prevented.     

Early mortality and AIDS progression despite high initial antiretroviral therapy adherence and virologic suppression in Botswana

Background

Adverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana.

Methods

This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%).

Results

Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1–4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4–4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively.

Conclusions

Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence.     

Predictors of poor CD4 and weight recovery in HIV-infected children initiating ART in South Africa

Objective

To identify baseline demographic and clinical risk factors associated with poor CD4 and weight response after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency virus (HIV)-infected children in KwaZulu-Natal, South Africa.

Methods

We performed a retrospective cohort study of 674 children initiating antiretroviral therapy at McCord and St. Mary''s hospitals in KwaZulu-Natal, South Africa, from August 2003 to December 2008.We extracted data from paper charts and electronic medical records to assess risk factors associated with CD4 and weight response using logistic regression.

Results

From the initial cohort of 901 children <10 years old initiating ART between August 2003 and December 2008, we analyzed 674 children with complete baseline data. Viral suppression rates (<400 copies/ml) were 84% after six months of therapy and 88% after 12 months of therapy. Seventy-three percent of children achieved CD4 recovery after six months and 89% after 12 months. Weight-for-age Z-score (WAZ) improvements were seen in 58% of children after six months of ART and 64% after 12 months. After six months of ART, lower baseline hemoglobin (p = 0.037), presence of chronic diarrhea (p = 0.007), and virologic failure (p = 0.046) were all associated with poor CD4 recovery by multivariate logistic regression. After 12 months of ART, poor CD4 recovery was associated with higher baseline CD4% (p = 0.005), chronic diarrhea (p = 0.02), and virologic failure (p<0.001). Age less than 3 years at ART initiation (p = 0.0003), higher baseline CD4% (p<0.001), and higher baseline WAZ (p<0.001) were all associated with poor WAZ improvements after 6 months by multivariate logistic regression.

Conclusion

The presence of chronic diarrhea at baseline, independent of nutritional status and viral response, predicts poor CD4 recovery. Age at initiation of ART is an important factor in early WAZ response to ART, while viral suppression strongly predicts CD4 recovery but not WAZ improvement.     

HIV status disclosure and retention in care in HIV-infected adolescents on antiretroviral therapy (ART) in West Africa

Objective

We assessed the effect of HIV status disclosure on retention in care from initiation of antiretroviral therapy (ART) among HIV-infected children aged 10 years or more in Cote d''Ivoire, Mali and Sénégal.

Methods

Multi-centre cohort study within five paediatric clinics participating in the IeDEA West Africa collaboration. HIV-infected patients were included in this study if they met the following inclusion criteria: aged 10–21 years while on ART; having initiated ART≥200 days before the closure date of the clinic database; followed ≥15 days from ART initiation in clinics with ≥10 adolescents enrolled. Routine follow-up data were merged with those collected through a standardized ad hoc questionnaire on awareness of HIV status. Probability of retention (no death or loss-to-follow-up) was estimated with Kaplan-Meier method. Cox proportional hazard model with date of ART initiation as origin and a delayed entry at date of 10th birthday was used to identify factors associated with death or loss-to-follow-up.

Results

650 adolescents were available for this analysis. Characteristics at ART initiation were: median age of 10.4 years; median CD4 count of 224 cells/mm³ (47% with severe immunosuppression), 48% CDC stage C/WHO stage 3/4. The median follow-up on ART after the age of 10 was 23.3 months; 187 adolescents (28.8%) knew their HIV status. The overall probability of retention at 36 months after ART initiation was 74.6% (95% confidence interval [CI]: 70.5–79.0) and was higher for those disclosed compared to those not: adjusted hazard ratio for the risk of being death or loss-to-follow-up = 0.23 (95% CI: 0.13–0.39).

Conclusion

About 2/3 of HIV-infected adolescents on ART were not aware of their HIV status in these ART clinics in West Africa but disclosed HIV status improved retention in care. The disclosure process should be thus systematically encouraged and organized in adolescent populations.     

Not all are lost: interrupted laboratory monitoring, early death, and loss to follow-up (LTFU) in a large South African treatment program

Background

Many HIV treatment programs in resource-limited settings are plagued by high rates of loss to follow-up (LTFU). Most studies have not distinguished between those who briefly interrupt, but return to care, and those more chronically lost to follow-up.

Methods

We conducted a retrospective cohort study of 11,397 adults initiating antiretroviral therapy (ART) in 71 Southern African Catholic Bishops Conference/Catholic Relief Services HIV treatment clinics between January 2004 and December 2008. We distinguished among patients with early death, within the first 7 months on ART; patients with interruptions in laboratory monitoring (ILM), defined as missing visits in the first 7 months on ART, but returning to care by 12 months; and those LTFU, defined as missing all follow-up visits in the first 12 months on ART. We used multilevel logistic regression models to determine patient and clinic-level characteristics associated with these outcomes.

Results

In the first year on ART, 60% of patients remained in care, 30% missed laboratory visits, and 10% suffered early death. Of the 3,194 patients who missed laboratory visits, 40% had ILM, resuming care by 12 months. After 12 months on ART, patients with ILM had a 30% increase in detectable viremia compared to those who remained in care. Risk of LTFU decreased with increasing enrollment year, and was lowest for patients who enrolled in 2008 compared to 2004 [OR 0.49, 95%CI 0.39–0.62].

Conclusions

In a large community-based cohort in South Africa, nearly 30% of patients miss follow-up visits for CD4 monitoring in the first year after starting ART. Of those, 40% have ILM but return to clinic with worse virologic outcomes than those who remain in care. The risk of chronic LTFU decreased with enrollment year. As ART availability increases, interruptions in care may become more common, and should be accounted for in addressing program LTFU.     

Will Adoption of the 2010 WHO ART Guidelines for HIV-Infected TB Patients Increase the Demand for ART Services in India?

Background

In 2010, WHO expanded previously-recommended indications for anti-retroviral treatment to include all HIV-infected TB patients irrespective of CD4 count. India, however, still limits ART to those TB patients with CD4 counts <350/mm³ or with extrapulmonary TB manifestations. We sought to evaluate the additional number of patients that would be initiated on ART if India adopted the current 2010 WHO ART guidelines for HIV-infected TB patients.

Methods

We evaluated all TB patients recorded in treatment registers of the Revised National TB Control Programme in June 2010 in the high-HIV prevalence state of Karnataka, and cross-matched HIV-infected TB patients with ART programme records.

Results

Of 6182 TB patients registered, HIV status was ascertained for 5761(93%) and 710(12%) were HIV-infected. 146(21%) HIV-infected TB patients were on ART prior to TB diagnosis. Of the remaining 564, 497(88%) were assessed for ART eligibility; of these, 436(88%) were eligible for ART according to 2006 WHO ART guidelines. Altogether, 487(69%) HIV-infected TB patients received ART during TB treatment. About 80% started ART within 8 weeks of TB treatment and 95% received an efavirenz based regimen.

Conclusion

In Karnataka, India, about nine out of ten HIV-infected TB patients were eligible for ART according to 2006 WHO ART guidelines. The efficiency of HIV case finding, ART evaluation, and ART initiation was relatively high, with 78% of eligible HIV-infected patients actually initiated on ART, and 80% within 8 weeks of diagnosis. ART could be extended to all HIV-infected TB patients irrespective of CD4 count with relatively little additional burden on the national ART programme.     

Association between Use of HMG CoA Reductase Inhibitors and Mortality in HIV-Infected Patients

Introduction

HIV infection is a disease associated with chronic inflammation and immune activation. Antiretroviral therapy reduces inflammation, but not to levels in comparable HIV-negative individuals. The HMG-coenzyme A reductase inhibitors (statins) inhibit several pro-inflammatory processes and suppress immune activation, and are a logical therapy to assess for a possible salutary effect on HIV disease progression and outcomes.

Methods

Eligible patients were patients enrolled in the Johns Hopkins HIV Clinical Cohort who achieved virologic suppression within 180 days of starting a new highly active antiretroviral therapy (HAART) regimen after January 1, 1998. Assessment was continued until death in patients who maintained a virologic suppression, with right-censoring of their follow-up time if they had an HIV RNA > 500 copies/ml. Cox proportional hazards regression was used to assess statin use as a time-varying covariate, as well as other demographic and clinical factors.

Results

A total of 1538 HIV-infected patients fulfilled eligibility criteria, of whom 238 (15.5%) received a statin while taking HAART. There were 85 deaths (7 in statin users, 78 in non-users). By multivariate Cox regression, statin use was associated with a relative hazard of 0.33 (95% CI: 0.14, 0.76; P = 0.009) after adjusting for CD4, HIV-1 RNA, hemoglobin and cholesterol levels at the start of HAART, age, race, HIV risk group, prior use of ART, year of HAART start, NNRTI vs. PI-based ART, prior AIDS-defining illness, and viral hepatitis coinfection. Malignancy, non-AIDS-defining infection and liver failure were particularly prominent causes of death.

Discussion

Statin use was associated with significantly lower hazard of dying in these HIV-infected patients who were being effectively treated with HAART as determined by virologic suppression. Our results suggest the need for confirmation in other observational cohorts, and if confirmed, the need for a clinical trial of statin use in HIV infection.     

Excellent adherence to antiretrovirals in HIV+ Zambian children is compromised by disrupted routine, HIV nondisclosure, and paradoxical income effects

Introduction

A better understanding of pediatric antiretroviral therapy (ART) adherence in sub-Saharan Africa is necessary to develop interventions to sustain high levels of adherence.

Methodology/Principal Findings

Adherence among 96 HIV-infected Zambian children (median age 6, interquartile range [IQR] 2,9) initiating fixed-dose combination ART was measured prospectively (median 23 months; IQR 20,26) with caregiver report, clinic and unannounced home-based pill counts, and medication event monitoring systems (MEMS). HIV-1 RNA was determined at 48 weeks. Child and caregiver characteristics, socio-demographic status, and treatment-related factors were assessed as predictors of adherence. Median adherence was 97.4% (IQR 96.1,98.4%) by visual analog scale, 94.8% (IQR 86,100%) by caregiver-reported last missed dose, 96.9% (IQR 94.5,98.2%) by clinic pill count, 93.4% (IQR 90.2,96.7%) by unannounced home-based pill count, and 94.8% (IQR 87.8,97.7%) by MEMS. At 48 weeks, 72.6% of children had HIV-1 RNA <50 copies/ml. Agreement among adherence measures was poor; only MEMS was significantly associated with viral suppression (p = 0.013). Predictors of poor adherence included changing residence, school attendance, lack of HIV disclosure to children aged nine to 15 years, and increasing household income.

Conclusions/Significance

Adherence among children taking fixed-dose combination ART in sub-Saharan Africa is high and sustained over two years. However, certain groups are at risk for treatment failure, including children with disrupted routines, no knowledge of their HIV diagnosis among older children, and relatively high household income, possibly reflecting greater social support in the setting of greater poverty.     

Antiretroviral therapy outcomes in HIV-infected children after adjusting protease inhibitor dosing during tuberculosis treatment

Background

Modification of ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy is required for HIV-infected children co-treated for tuberculosis (TB). We aimed to determine virologic and toxicity outcomes among TB/HIV co-treated children with the following modifications to their antiretroviral therapy (ART): (1) super-boosted LPV/r, (2) double-dose LPV/r or (3) ritonavir.

Methods and Findings

A medical record review was conducted at two clinical sites in Johannesburg, South Africa. The records of children 6–24 months of age initiating LPV/r-based therapy were reviewed. Children co-treated for TB were categorized based on the modifications made to their ART regimen and were compared to children of the same age at each site not treated for TB.Included are 526 children, 294 (56%) co-treated for TB. All co-treated children had more severe HIV disease, including lower CD4 percents and worse growth indicators, than comparisons.Children in the super-boosted group (n = 156) were as likely to be virally suppressed (<400 copies/ml) at 6 months as comparisons (69.2% vs. 74.8%, p = 0.36). Children in the double-dose (n = 47) and ritonavir groups (n = 91) were significantly less likely to be virally suppressed at 6 months (53.1% and 49.3%) than comparisons (74.8% and 82.1%; p = 0.02 and p<0.0001, respectively). At 12 months only children in the ritonavir group still had lower rates of virological suppression relative to comparisons (63.9% vs 83.3% p<0.05). Grade 1 or greater ALT elevations were more common in the super-boosted (75%) than double-dose (54.6%) or ritonavir (33.9%) groups (p = 0.09 and p<0.0001) but grade 3/4 elevations were observed in 3 (13.6%) of the super-boosted, 7 (15.9%) of the double-dose and 5 (8.9%) of the ritonavir group (p = 0.81 and p = 0.29).

Conclusion

Good short-term virologic outcomes were achieved in children co-treated for TB and HIV who received super-boosted LPV/r. Treatment limiting toxicity was rare. Strategies for increased dosing of LPV/r with TB treatment warrant further investigation.     

Incidence and predictors of immune reconstitution inflammatory syndrome in a rural area of Mozambique

Background

There is limited data on the epidemiology of Immune Reconstitution Inflammatory Syndrome (IRIS) in rural sub-Saharan Africa. A prospective observational cohort study was conducted to assess the incidence, clinical characteristics, outcome and predictors of IRIS in rural Mozambique.

Methods

One hundred and thirty-six consecutive antiretroviral treatment (ART)-naïve HIV-1-infected patients initiating ART at the Manhiça district hospital were prospectively followed for development of IRIS over 16 months. Survival analysis by Cox regression was performed to identify pre-ART predictors of IRIS development.

Results

Thirty-six patients developed IRIS [26.5%, incidence rate 3.1 cases/100 persons-month of ART (95% CI 2.2–4.3)]. Median time to IRIS onset was 62 days from ART initiation (IQR 35.5–93.5). Twenty-five cases (69.4%) were “unmasking”, 10 (27.8%) were “paradoxical”, and 1 (2.8%) developed a paradoxical worsening followed by the unmasking of another condition. Systemic OI (OI-IRIS) accounted for 47% (17/36) of IRIS cases, predominantly of KS (8 cases) and TB (6 cases) IRIS. Mucocutaneous IRIS manifestations (MC-IRIS) accounted for 53% (19/36) of IRIS events, mostly tinea (9 cases) and herpes simplex infection (3 cases). Multivariate analysis identified two independent predictors of IRIS development: pre-ART CD4 count <50 cells/µl (HR 2.3, 95% CI 1.19–4.44, p = 0.01) and body mass index (BMI) <18.5 (HR 2.15, 95% CI 1.07–4.3, p = 0.03). The pre-cART proportion of activated T-cells, as well as the immunologic and virologic response to ART were not associated with IRIS development. All patients continued on ART, 7 (19.4%) required hospitalization and there were 3 deaths (8.3%) attributable to IRIS.

Conclusions

IRIS is common in patients initiating ART in rural Mozambique. Pre-ART CD4 counts and BMI can easily be assessed at ART initiation in rural sub-Saharan Africa to identify patients at high risk of IRIS, for whom close supervision is warranted.     

HIV-infected children living in Central Africa have low persistence of antibodies to vaccines used in the Expanded Program on Immunization

Background

The Expanded Program on Immunization (EPI) is the most cost-effective measures to control vaccine-preventable diseases. Currently, the EPI schedule is similar for HIV-infected children; the introduction of antiretroviral therapy (ART) should considerably prolong their life expectancy.

Methods and Principal Findings

To evaluate the persistence of antibodies to the EPI vaccines in HIV-infected and HIV-exposed uninfected children who previously received these vaccines in routine clinical practice, we conducted a cross-sectional study of children, aged 18 to 36 months, born to HIV-infected mothers and living in Central Africa. We tested blood samples for antibodies to the combined diphtheria, tetanus, and whole-cell pertussis (DTwP), the measles and the oral polio (OPV) vaccines. We enrolled 51 HIV-infected children of whom 33 were receiving ART, and 78 HIV-uninfected children born to HIV-infected women. A lower proportion of HIV-infected children than uninfected children had antibodies to the tested antigens with the exception of the OPV types 1 and 2. This difference was substantial for the measles vaccine (20% of the HIV-infected children and 56% of the HIV-exposed uninfected children, p<0.0001). We observed a high risk of low antibody levels for all EPI vaccines, except OPV types 1 and 2, in HIV-infected children with severe immunodeficiency (CD4⁺ T cells <25%).

Conclusions and Significance

Children were examined at a time when their antibody concentrations to EPI vaccines would have still not undergone significant decay. However, we showed that the antibody concentrations were lowered in HIV-infected children. Moreover, antibody concentration after a single dose of the measles vaccine was substantially lower than expected, particularly low in HIV-infected children with low CD4⁺ T cell counts. This study supports the need for a second dose of the measles vaccine and for a booster dose of the DTwP and OPV vaccines to maintain the antibody concentrations in HIV-infected and HIV-exposed uninfected children.     

Gender difference in 2-year mortality and immunological response to ART in an HIV-infected Chinese population, 2006-2008

Background

Since it was initiated in 2002, the China Free Antiretroviral Treatment (ART) Program has been progressing from an emergency response to a standardized treatment and care system. As of December 31, 2009, a total of 81,880 patients in 31 provinces, autonomous regions, and special municipalities received free ART. Gender differences, however, in mortality and immunological response to ART in this cohort have never been described.

Objective

To understand whether women and men who enrolled in the China National Free ART Program responded equally well to the treatment.

Methods

A retrospective analysis of the national free ART databases from June 2006–December 2008 was performed. HIV-infected subjects who were 18 years or older, ART naïve at baseline, and on a 3TC regimen enrolled in the program from June 1 to December 31, 2006, were included in this study, then followed up to 2 years.

Results

Among 3457 enrolled subjects who met the inclusion criteria, 59.2% were male and 40.8% female. The majority of the subjects were 19–44 years old (77%) and married (72%). Over the full 24 months of follow-up, the mortality rate was 19.0% in males and 11.4% in females (p = 0.0014). Males on therapy for 3–24 months were more likely to die than females (HR = 1.46, 95% CI: 1.04–2.06, p = 0.0307) after adjusting for baseline characteristics. Compared to men, women had higher CD4+ counts over time after initiating ART (p<0.0001).

Conclusions

Our study showed that women had an overall lower mortality and higher CD4+ counts than men in response to ART treatment, which may be attributed to adherence, biological factors, social, cultural and economic reasons. Further study is needed to explore these factors that might contribute to the gender differences in mortality and immunological response to ART.     

Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART) in South Africa

Objective

To identify demographic and clinical risk factors associated with mortality after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency (HIV) infected children in KwaZulu-Natal, South Africa.

Methods

We performed a retrospective cohort study of 537 children initiating antiretroviral therapy at McCord Hospital in KwaZulu-Natal, South Africa. Data were extracted from electronic medical records and risk factors associated with mortality were assessed using Cox regression analysis.

Results

Overall there were 47 deaths from the cohort of 537 children initiating ART with over 991 child-years of follow-up (median 22 months on ART), yielding a mortality rate of 4.7 deaths per 100 child years on ART. Univariate analysis indicated that mortality was significantly associated with lower weight-for-age Z-score (p<0.0001), chronic diarrhea (p = 0.0002), lower hemoglobin (p = 0.002), age <3 years (p = 0.003), and CD4% <10% (p = 0.005). The final multivariable Cox proportional hazards mortality model found age less than 3 years (p = 0.004), CD4 <10% (p = 0.01), chronic diarrhea (p = 0.03), weight-for-age Z-score (<0.0001) and female gender as a covariate varying with time (p = 0.03) all significantly associated with mortality.

Conclusion

In addition to recognized risk factors such as young age and advanced immunosuppression, we found female gender to be significantly associated with mortality in this pediatric ART cohort. Future studies are needed to determine whether intrinsic biologic differences or socio-cultural factors place female children with HIV at increased risk of death following initiation of ART.     

Antiretroviral treatment for HIV in rural Uganda: two-year treatment outcomes of a prospective health centre/community-based and hospital-based cohort

Background

In sub-Saharan Africa, a shortage of trained health professionals and limited geographical access to health facilities present major barriers to the expansion of antiretroviral therapy (ART). We tested the utility of a health centre (HC)/community-based approach in the provision of ART to persons living with HIV in a rural area in western Uganda.

Methods

The HIV treatment outcomes of the HC/community-based ART program were evaluated and compared with those of an ART program at a best-practice regional hospital. The HC/community-based cohort comprised 185 treatment-naïve patients enrolled in 2006. The hospital cohort comprised of 200 patients enrolled in the same time period. The HC/community-based program involved weekly home visits to patients by community volunteers who were trained to deliver antiretroviral drugs to monitor and support adherence to treatment, and to identify and report adverse reactions and other clinical symptoms. Treatment supporters in the homes also had the responsibility to remind patients to take their drugs regularly. ART treatment outcomes were measured by HIV-1 RNA viral load (VL) after two years of treatment. Adherence was determined through weekly pill counts.

Results

Successful ART treatment outcomes in the HC/community-based cohort were equivalent to those in the hospital-based cohort after two years of treatment in on-treatment analysis (VL≤400 copies/mL, 93.0% vs. 87.3%, p = 0.12), and in intention-to-treat analysis (VL≤400 copies/mL, 64.9% and 62.0%, p = 0.560). In multivariate analysis patients in the HC/community-based cohort were more likely to have virologic suppression compared to hospital-based patients (adjusted OR = 2.47, 95% CI 1.01–6.04).

Conclusion

Acceptable rates of virologic suppression were achieved using existing rural clinic and community resources in a HC/community-based ART program run by clinical officers and supported by lay volunteers and treatment supporters. The results were equivalent to those of a hospital-based ART program run primarily by doctors.     

Diminishing availability of publicly funded slots for antiretroviral initiation among HIV-infected ART-eligible patients in Uganda

Background

The impact of flat-line funding in the global scale up of antiretroviral therapy (ART) for HIV-infected patients in Africa has not yet been well described.

Methods

We evaluated ART-eligible patients and patients starting ART at a prototypical scale up ART clinic in Mbarara, Uganda between April 1, 2009 and May 14, 2010 where four stakeholders sponsor treatment – two PEPFAR implementing organizations, the Ugandan Ministry of Health – Global Fund (MOH-GF) and a private foundation named the Family Treatment Fund (FTF). We assessed temporal trends in the number of eligible patients, the number starting ART and tabulated the distribution of the stakeholders supporting ART initiation by month and quartile of time during this interval. We used survival analyses to assess changes in the rate of ART initiation over calendar time.

Findings

A total of 1309 patients who were eligible for ART made visits over the 14 month period of the study and of these 819 started ART. The median number of ART eligible patients each month was 88 (IQR: 74 to 115). By quartile of calendar time, PEPFAR and MOH sponsored 290, 192, 180, and 49 ART initiations whereas the FTF started 1, 2, 1 and 104 patients respectively. By May of 2010 (the last calendar month of observation) FTF sponsored 88% of all ART initiations. Becoming eligible for ART in the 3^rd (HR = 0.58, 95% 0.45–0.74) and 4^th quartiles (HR = 0.49, 95% CI: 0.36–0.65) was associated with delay in ART initiation compared to the first quartile in multivariable analyses.

Interpretation

During a period of flat line funding from multinational donors for ART programs, reductions in the number of ART initiations by public programs (i.e., PEPFAR and MOH-GF) and delays in ART initiation became apparent at the a large prototypical scale-up ART clinic in Uganda.     

Association of age with mortality and virological and immunological response to antiretroviral therapy in rural South African adults

Objective

To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort.

Design

Retrospective cohort analysis using data from a public HIV Treatment & Care Programme.

Methods

Adults initiating ART 1^st August 2004 - 31^st October 2009 were stratified by age at initiation: young adults (16–24 years) mid-age adults (25–49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points.

Results

8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25–49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90–7.78); 6.55 (95% CI 6.11–7.02) and 8.69 (95% CI 7.34–10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0–3 months (MR: 27.1 vs 17.17 and 21.36) and 3–12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0–3 months) whilst immunological and virological responses were associated with mortality after 12months.

Conclusions

Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART.     

Combining qualitative and quantitative evidence to determine factors leading to late presentation for antiretroviral therapy in Malawi

Background

Treatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa.

Objective

To better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural Malawi.

Methods

Qualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009.

Results

43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women''s frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men''s commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3–3.9) and never being married (adjusted OR 4.1, 95% CI1.5–11.5) were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15–0.63),compared to those with no dependent children.

Conclusion

Gender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.     

Ambulatory multi-drug resistant tuberculosis treatment outcomes in a cohort of HIV-infected patients in a slum setting in Mumbai, India

Background

India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India.

Methods

HIV-infected patients with suspected MDR-TB were referred to the MSF-clinic by public Antiretroviral Therapy (ART) Centers or by a network of community non-governmental organizations. Patients were initiated on either empiric or individualized second-line TB-treatment as per WHO recommendations. MDR-TB treatment was given on an ambulatory basis and under directly observed therapy using a decentralized network of providers. Patients not already receiving ART were started on treatment within two months of initiating MDR-TB treatment.

Results

Between May 2007 and May 2011, 71 HIV-infected patients were suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final treatment outcomes were available for 23 patients; 11 (48%) were successfully treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall, among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%) died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and still on treatment at the end of the observation period. Twenty-six patients (45%) experienced moderate to severe adverse events, requiring modification of the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died, including 7 not initiated on treatment.

Conclusions

Despite high fluoroquinolone resistance and extensive prior second-line treatment, encouraging results are being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid scale-up of both ART and second-line treatment for MDR-TB is needed to ensure survival of co-infected patients and mitigate this growing epidemic.     

Predictive Factors of Plasma HIV Suppression during Pregnancy: A Prospective Cohort Study in Benin

Objective

To investigate the factors associated with HIV₁ RNA plasma viral load (pVL) below 40 copies/mL at the third trimester of pregnancy, as part of prevention of mother-to-child transmission (PMTCT) in Benin.

Design

Sub study of the PACOME clinical trial of malaria prophylaxis in HIV-infected pregnant women, conducted before and after the implementation of the WHO 2009 revised guidelines for PMTCT.

Methods

HIV-infected women were enrolled in the second trimester of pregnancy. Socio-economic characteristics, HIV history, clinical and biological characteristics were recorded. Malaria prevention and PMTCT involving antiretroviral therapy (ART) for mothers and infants were provided. Logistic regression helped identifying factors associated with virologic suppression at the end of pregnancy.

Results

Overall 217 third trimester pVLs were available, and 71% showed undetectability. Virologic suppression was more frequent in women enrolled after the change in PMTCT recommendations, advising to start ART at 14 weeks instead of 28 weeks of pregnancy. In multivariate analysis, Fon ethnic group (the predominant ethnic group in the study area), regular job, first and second pregnancy, higher baseline pVL and impaired adherence to ART were negative factors whereas higher weight, higher antenatal care attendance and longer ART duration were favorable factors to achieve virologic suppression.

Conclusions

This study provides more evidence that ART has to be initiated before the last trimester of pregnancy to achieve an undetectable pVL before delivery. In Benin, new recommendations supporting early initiation were well implemented and, together with a high antenatal care attendance, led to high rate of virologic control.