Tuberculosis Case Fatality and Other Causes of Death among Multidrug-Resistant Tuberculosis Patients in a High HIV Prevalence Setting, 2000-2008, South Africa

Introduction

South Africa has the highest reported rates of multi-drug resistant TB in Africa, typified by poor treatment outcomes, attributable mainly to high default and death rates. Concomitant HIV has become the strongest predictor of death among MDR-TB patients, while anti-retroviral therapy (ART) has dramatically reduced mortality. TB Case fatality rate (CFR) is an indicator that specifically reports on deaths due to TB.

Aim

The aim of this paper was to investigate causes of death amongst MDR-TB patients, the contribution of conditions other than TB to deaths, and to determine if causes differ between HIV-uninfected patients, HIV-infected patients receiving ART and those without ART.

Methods

We carried out a retrospective review of data captured from the register of the MDR-TB programme of the North West Province, South Africa. We included 671 patients treated between 2000–2008; 59% of the cohort was HIV-infected and 33% had received ART during MDR treatment. The register contained data on treatment outcomes and causes of death.

Results

Treatment outcomes between HIV-uninfected cases, HIV-infected cases receiving ART and HIV-infected without ART differed significantly (p<0.000). The cohort death rate was 24%, 13% for HIV-uninfected cases and 31% for HIV-infected cases. TB caused most of the deaths, resulting in a cohort CFR of 15%, 9% for HIV-uninfected cases and 20% for HIV-infected cases. Cohort mortality rate due to other conditions was 2%. AIDS-conditions rather than TB caused significantly more deaths among HIV-infected cases receiving ART than those not (p = 0.02).

Conclusions

The deaths among HIV-infected individuals contribute substantially to the high death rate. ART co-therapy protected HIV-infected cases from death due to TB and AIDS-conditions. Mechanisms need to be in place to ensure that HIV-infected individuals are retained in care upon completion of their MDR-TB treatment.     

Reasons for Missing Antiretroviral Therapy: Results from a Multi-Country Study in Tanzania,Uganda, and Zambia

Objectives

To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence.

Methods

Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (≥18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients’ medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months.

Results

Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2–7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1–1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms.

Conclusions

Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes.     

Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha,South Africa: Impact on Mortality and Treatment Success

Setting

Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.

Objective

To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.

Design

A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.

Results

Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm³. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2–8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1–18.1), CD4 count ≤100 (aHR 2.1, CI 1.0–4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1–5.4).

Conclusions

Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.     

A Description of Mortality Associated with IPT plus ART Compared to ART Alone among HIV-Infected Individuals in Addis Ababa,Ethiopia: A Cohort Study

Background

Tuberculosis (TB) is the most common human immunodeficiency virus (HIV) associated opportunistic infection. It is the leading cause of death in HIV-infected individuals in sub-Saharan Africa. Anti-retroviral therapy (ART) and isoniazid preventive therapy (IPT) are the two useful TB preventative strategies available to reduce TB among people living with HIV (PLHIV). Therefore, the aim of this study is to compare mortality associated with IPT taken together with ART, as well as ART alone, among PLHIV.

Methods

A retrospective cohort study was undertaken at Tikur Anbessa Specialized Hospital (TASH) and Zewditu Memorial Hospital (ZMH) on 185 patients receiving IPT (6 months) plus ART and 557 patients receiving ART alone. Mortality rates (MR) per 100 person-years (PYs) were used to compare mortality rates amongst the groups. Time-to-death and survival probabilities of the patients were determined using the Kaplan Meier Method. The Cox Proportional Hazard Model was employed to estimate the effect of IPT plus ART on survival of PLHIV.

Results

The mortality cases noted in patients treated by IPT plus ART versus ART alone were 18 (4.5 cases/100 PYs) and 116 (10 cases/100 PYs), respectively. In reference to the ART alone, the IPT plus ART reduced the likelihood of death significantly (aHR 0.48; 95% CI 0.38–0.69) and median time to death was about 26 months (IQR 19–34). Moreover, WHO stage IV (aHR 2.42: 95% CI 1.42–4.11), CD4 values ≥350cells/mm3 (aHR 0.52; 95% CI 0.28–0.94), adherence to ART (aHR 0.12; 95% CI 0.08–0.20), primary levels of education (aHR 2.20; 95% CI 1.07–4.52); and alcohol consumption (aHR 1.71; 95% CI 1.04–2.81) were factors strongly associated with mortality.

Conclusion

We found that PLHIV treated by the IPT plus ART had a lower likelihood of mortality and delayed time-to-death when compared to patients treated by ART alone.     

Post-ART Symptoms Were Not the Problem: A Qualitative Study on Adherence to ART in HIV-Infected Patients in a Mozambican Rural Hospital

Objective

The objective of this qualitative study was to explore how clinical symptoms may affect adherence to antiretroviral therapy (ART) in HIV patients, and to explore factors, perceptions and attitudes related to adherence to therapy.

Design

A qualitative study was carried out in the context of the prospective cohort study “Evaluation of Immune Reconstitution Following Initiation of Highly Active Antiretroviral Treatment in Manhiça, Mozambique”. In-depth Interviews were conducted twice in a sub-sample of the study cohort (51 participants), at six-month intervals.

Results

Most participants (73%) knew that AIDS is a chronic disease and that ART does not cure it. Nine participants (18%) were non-adherent at some point and two (4%) abandoned ART. All participants but five reported having symptoms after starting ART, mainly attributed to pills needing time to act and body’s reaction to the treatment. In spite of the perceived severity of the symptoms, only two people reported they discontinued the treatment due to symptoms. Almost all participants reported feeling comfortable with the HIV clinic organization and procedures, but afraid of staff being hostile if they did not follow the rules or if the health worker visited their home. Family was one of the most important source of support according participants. Almost all participants with children said that a decisive factor to follow the treatment was the desire to be able to look after them.

Conclusions

Experiencing symptoms after starting treatment was not a barrier to adherence to ART. Factors related to adherence included control measures set up by the health facility (exhaustive follow up, support, information) and family and community support. Indirect ART-related expenses did jeopardise adherence.     

Antiretroviral Therapy,Especially Efavirenz,Is Associated with Low Bone Mineral Density in HIV-Infected South Africans

Purpose

We determined the prevalence and correlates of low bone mineral density (BMD) in HIV-infected South Africans as there is a paucity of such data from Africa.

Methods

BMD and serum 25-hydroxyvitamin D were measured in HIV-positive participants on antiretroviral therapy (ART) and in those not yet on ART (ART-naïve).

Results

We enrolled 444 participants [median age 35(IQR: 30, 40) years; 77% women]. BMD was low (z score <-2SD) in 17% and 5% of participants at the lumbar spine and total hip, respectively. Total hip [0.909 (SD 0.123) vs 0.956 (SD 0.124) g/cm², p = 0.0001] and neck of femur BMD [0.796 (SD 0.130) vs 0.844 (SD 0.120) g/cm², p = 0.0001] were lower in the ART, compared to the ART-naïve group. Vitamin D deficiency was present in 15% of participants and was associated with efavirenz use [adjusted OR 2.04 (95% CI 1.01 to 4.13)]. In a multivariate linear regression, exposure to efavirenz or lopinavir-based ART was associated with lower total hip BMD, whereas higher weight, being male and higher vitamin D concentration were associated with higher total hip BMD (adjusted R² = 0.28). Age, weight, sex, and the use of efavirenz-based ART were independently associated with lumbar spine BMD (adjusted R² = 0.13).

Conclusions

Vitamin D status, use of efavirenz or lopinavir/ritonavir, weight, age and sex are significantly associated with lower BMD in this young cohort of HIV-infected South Africans.     

Glucose Metabolism Disorders,HIV and Antiretroviral Therapy among Tanzanian Adults

Introduction

Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.

Methods

In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.

Results

HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.

Conclusions

HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.     

A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy

Objective

We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin.

Design

Cohort study of adult patients on ART.

Setting

GHESKIO Clinic in Port-au-Prince, Haiti.

Participants

4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008.

Main Outcome Measure

Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin.

Results

In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30–2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used.

Conclusions

If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted.     

Incidence of AIDS-Defining Opportunistic Infections and Mortality during Antiretroviral Therapy in a Cohort of Adult HIV-Infected Individuals in Hanoi, 2007-2014

Background

Although the prognosis for HIV-infected individuals has improved after antiretroviral therapy (ART) scale-up, limited data exist on the incidence of AIDS-defining opportunistic infections (ADIs) and mortality during ART in resource-limited settings.

Methods

HIV-infected adults in two large hospitals in urban Hanoi were enrolled to the prospective cohort, from October 2007 through December 2013. Those who started ART less than one year before enrollment were assigned to the survival analysis. Data on ART history and ADIs were collected retrospectively at enrollment and followed-up prospectively until April 2014.

Results

Of 2,070 cohort participants, 1,197 were eligible for analysis and provided 3,446 person-years (PYs) of being on ART. Overall, 161 ADIs episodes were noted at a median of 3.20 months after ART initiation (range 0.03–75.8) with an incidence 46.7/1,000 PYs (95% confidence interval [CI] 39.8–54.5). The most common ADI was tuberculosis with an incidence of 29.9/1,000 PYs. Mortality after ART initiation was 8.68/1,000 PYs and 45% (19/45) died of AIDS-related illnesses. Age over 50 years at ART initiation was significantly associated with shorter survival after controlling for baseline CD4 count, but neither having injection drug use (IDU) history nor previous ADIs were associated with poor survival. Semi-competing risks analysis in 951 patients without ADIs history prior to ART showed those who developed ADIs after starting ART were at higher risk of death in the first six months than after six months.

Conclusion

ADIs were not rare in spite of being on effective ART. Age over 50 years, but not IDU history, was associated with shorter survival in the cohort. This study provides in-depth data on the prognosis of patients on ART in Vietnam during the first decade of ART scale-up.     

Comparisons of Adherence to Antiretroviral Therapy in a High- Risk Population in China: A Systematic Review and Meta-Analysis

Background

Reports on antiretroviral therapy (ART) adherence are scare in China; we performed this meta-analysis to estimate ART adherence rates in different populations at high risk for HIV transmission in China.

Methods

We searched PubMed, Chinese Biomedical Literature Database (Chinese), China National Knowledge Infrastructure (Chinese), and Wanfang (Chinese) to identify studies published from January 1985 to May 2015. We used random-effects meta-analysis to calculate weighted mean estimates across studies and 95% CIs. Data were pooled with proportions transformed prior to pooling using the Freeman–Tukey double arcsine transformation and then back transformed to the original scale. We calculated the I² (and its 95% confidence intervals) and tau² to assess between-study heterogeneity.

Results

We identified 36 eligible articles, including 6885 HIV-positive individuals, reporting ART adherence. Pooled analysis produced an estimate of 77.61% (95% CI = 71.63–83.08) of patients with HIV with adequate adherence; however, high heterogeneity was observed between studies (I² = 96.60%, 95%CI = 96.00%-97.20%; tau² = 0.16). Three studies, which included 149 old HIV-infected patients, reported the highest ART adequate adherence rate (89.39%, 95% CI = 72.01–99.26) with high heterogeneity between the studies (I² = 86.20%, 95%CI = 60.00–95.20%; tau² = 0.13). While, only two studies, which included 143 heterosexual transmission group (HTG) patients, reported the lowest ART adequate adherence rate (51.55%, 95% CI = 41.33–61.71) with low heterogeneity between the studies (I² = 31.3%, tau² = 0.007). In the multivariable meta-regression model, high-risk populations was the main factor explaining heterogeneity (variance explained 28.14%).

Conclusions

ART adherence in some high-risk populations (e.g., heterosexual transmission group) is below the recommended levels for maintaining virologic suppression. It is crucial to develop comprehensive intervention strategies to promote ART adherence in high-risk populations and effectively prevent the spread of HIV/AIDS in China.     

A Systematic Review of Individual and Contextual Factors Affecting ART Initiation,Adherence, and Retention for HIV-Infected Pregnant and Postpartum Women

Background

Despite progress reducing maternal mortality, HIV-related maternal deaths remain high, accounting, for example, for up to 24 percent of all pregnancy-related deaths in sub-Saharan Africa. Antiretroviral therapy (ART) is effective in improving outcomes among HIV-infected pregnant and postpartum women, yet rates of initiation, adherence, and retention remain low. This systematic literature review synthesized evidence about individual and contextual factors affecting ART use among HIV-infected pregnant and postpartum women.

Methods

Searches were conducted for studies addressing the population (HIV-infected pregnant and postpartum women), intervention (ART), and outcomes of interest (initiation, adherence, and retention). Quantitative and qualitative studies published in English since January 2008 were included. Individual and contextual enablers and barriers to ART use were extracted and organized thematically within a framework of individual, interpersonal, community, and structural categories.

Results

Thirty-four studies were included in the review. Individual-level factors included both those within and outside a woman’s awareness and control (e.g., commitment to child’s health or age). Individual-level barriers included poor understanding of HIV, ART, and prevention of mother-to-child transmission, and difficulty managing practical demands of ART. At an interpersonal level, disclosure to a spouse and spousal involvement in treatment were associated with improved initiation, adherence, and retention. Fear of negative consequences was a barrier to disclosure. At a community level, stigma was a major barrier. Key structural barriers and enablers were related to health system use and engagement, including access to services and health worker attitudes.

Conclusions

To be successful, programs seeking to expand access to and continued use of ART by integrating maternal health and HIV services must identify and address the relevant barriers and enablers in their own context that are described in this review. Further research on this population, including those who drop out of or never access health services, is needed to inform effective implementation.     

A Systematic Review of Health System Barriers and Enablers for Antiretroviral Therapy (ART) for HIV-Infected Pregnant and Postpartum Women

Background

Despite global progress in the fight to reduce maternal mortality, HIV-related maternal deaths remain persistently high, particularly in much of Africa. Lifelong antiretroviral therapy (ART) appears to be the most effective way to prevent these deaths, but the rates of three key outcomes—ART initiation, retention in care, and long-term ART adherence—remain low. This systematic review synthesized evidence on health systems factors affecting these outcomes in pregnant and postpartum women living with HIV.

Methods

Searches were conducted for studies addressing the population of interest (HIV-infected pregnant and postpartum women), the intervention of interest (ART), and the outcomes of interest (initiation, adherence, and retention). Quantitative and qualitative studies published in English since January 2008 were included. A four-stage narrative synthesis design was used to analyze findings. Review findings from 42 included studies were categorized according to five themes: 1) models of care, 2) service delivery, 3) resource constraints and governance challenges, 4) patient-health system engagement, and 5) maternal ART interventions.

Results

Low prioritization of maternal ART and persistent dropout along the maternal ART cascade were key findings. Service delivery barriers included poor communication and coordination among health system actors, poor clinical practices, and gaps in provider training. The few studies that assessed maternal ART interventions demonstrated the importance of multi-pronged, multi-leveled interventions.

Conclusions

There has been a lack of emphasis on the experiences, needs and vulnerabilities particular to HIV-infected pregnant and postpartum women. Supporting these women to successfully traverse the maternal ART cascade requires carefully designed and targeted interventions throughout the steps. Careful design of integrated service delivery models is of critical importance in this effort. Key knowledge gaps and research priorities were also identified, including definitions and indicators of adherence rates, and the importance of cumulative measures of dropout along the maternal ART cascade.     

Clinical,Virologic, Immunologic Outcomes and Emerging HIV Drug Resistance Patterns in Children and Adolescents in Public ART Care in Zimbabwe

Objective

To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country.

Methods

A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years) and adolescents (10–19 years) attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record.

Results

Data from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001). The median age at ART initiation was 8.0 years (IQR 3.0, 12.0); median time on ART was 2.9 years (IQR 1.7, 4.5). On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years) at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001). Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180). Children (<10y) on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239). In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324), and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379) were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates.

Conclusions

During routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes.     

Hepatitis B and C Co-Infection in HIV Patients from the TREAT Asia HIV Observational Database: Analysis of Risk Factors and Survival

Background

We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.

Methods

Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

Results

A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

Conclusion

In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.     

Outcomes in a Cohort of Patients Started on Antiretroviral Treatment and Followed up for a Decade in an Urban Clinic in Uganda

Background

Short-medium term studies from sub-Saharan Africa show that, despite high early mortality, substantial loss to program, and high rates toxicity, patients on antiretroviral treatment have achieved outcomes comparable to those in developed settings. However, these studies were unable to account for long term outcomes of patients as they stayed longer on treatment.

Objectives

We aim to describe ten years outcomes of one of the first cohort of HIV positive patients started on antiretroviral treatment (ART) in Sub-Saharan Africa.

Methods

We report 10-years outcomes including mortality, retention, CD4-count response, virological outcomes, ART regimens change from a prospective cohort of 559 patients initiating ART and followed up for 10 years Uganda.

Results

Of 559 patients, 69.1% were female, median age (IQR) was 38 (33–44) years, median CD4-count (IQR) 98 (21–163) cell/μL; 74% were started on stavudine, lamivudine and nevirapine, 26% on zidovudine, lamivudine and efavirenz. After 10 years 361 (65%) patients were still in the study; 127 (22.7%) had died; 30 (5%) were lost to follow-up; 27 (5%) transferred; 18 (3%) withdrew consent. The probability of death was high in the first year (0.15, 95%, CI 0.12–0.18). The median CD4 count increased from 98 to 589 cell/μL (IQR: 450–739 cell/μL) with a median increase of 357 cells/μL (IQR: 128–600 cells/μL); 7.4% never attained initial viral suppression and of those who did 31.7% experienced viral failure. Three hundred and two patients had at least one drug substitution while on first line after a median of 40 months; 66 (11.9%) of the patients were switched to a second line PI-based regimen due to confirmed treatment failure.

Conclusions

Despite the high rate of early mortality due to advanced disease at presentation the outcomes from this cohort are encouraging, particularly the remarkable and incremental immune-recovery and a satisfactory rate of virologic suppression.     

Dried Blood Spots for Viral Load Monitoring in Malawi: Feasible and Effective

Objectives

To evaluate the feasibility and effectiveness of dried blood spots (DBS) use for viral load (VL) monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa.

Methods

We recruited adult antiretroviral therapy (ART) patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt) and effectiveness (second-line therapy initiation).

Results

We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8%) of participants with elevated baseline VL had suppressed (<5,000 copies/ml) on confirmatory testing. Median period between enrollment and specimen testing was 23 days. Adjusting for relevant covariates, participants on ART >4 years were more likely to be failing than participants on therapy 1–4 years (RR 1.7, 95% CI 1.0-2.8); older participants were less likely to be failing (RR 0.95, 95% CI 0.92-0.98). There was no difference in likelihood of failure based on clinical symptoms (RR 1.17, 95% CI 0.65-2.11).

Conclusions

DBS for VL monitoring is feasible and effective in real-world clinical settings. Centralized DBS testing may increase access to VL monitoring in remote settings. Programmatic outcomes are encouraging, especially proportion of eligible participants switched to second-line therapy.     

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.