pre-ART Period Research Articles

Kaposi sarcoma-associated herpesvirus, HIV-1 and Kaposi sarcoma risk in black South Africans diagnosed with cancer during antiretroviral treatment rollout.

Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV-immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7886 black South Africans (18-74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV-1 and KSHV before and after ART rollout. We measured seropositivity to HIV-1, KSHV latency-associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case-control-adjusted odds ratios (ORadj ) and 95% confidence intervals (CI) in relation to KS and KSHV infection, before (1995-2004), early (2005-2009) and late (2010-2016) ART rollout periods. KSHV seropositivity among 1237 KS cases was 98%. Among 6649 controls, KSHV seropositivity was higher in males (ORadj =1.4 [95%CI 1.23-1.52]), in persons with HIV, (ORadj =4.2 [95%CI 3.74-4.73]) and lower in high school leavers (ORadj =0.7 [95%CI 0.59-0.83]). KSHV seropositivity declined over the three ART rollout periods (37%, 28% and 28%, Ptrend < .001) coinciding with increases in high school leavers over the same periods (46%, 58% and 67%, Ptrend < .001). HIV-1 seroprevalence increased from 10% in the pre-ART period to 22% in the late ART period (Ptrend < .001). Compared to HIV-1 and KSHV seronegatives, KSHV seropositives yielded an OR for KS of 26 (95%CI 11-62) in HIV-1 seronegative participants and an OR of 2501 (95%CI 1083-5776) in HIV-1 seropositive participants. HIV-1 increases the risk of KS in those infected with KSHV by 100-fold. Declines in KSHV seroprevalence coincide with ART rollout and with improvements in educational standards and general hygiene.

Reaching the Unreached: Providing Quality Care to HIV-Infected Children through Telemedicine-An Innovative Pilot Initiative from Maharashtra, India.

Background The National AIDS Control Organization (NACO) of India created the Regional Pediatric Antiretroviral Therapy (ART) Center; this was subsequently upgraded to seven Pediatric Centers of Excellence (PCoEs) to strengthen the quality of treatment and care of children living with HIV/AIDS (CLHAs). In October 2013, the pediatric HIV telemedicine initiative, an e-decentralized (care provided by local healthcare providers and support provided by a central agency through telemedicine facilities) model of expert pediatric HIV care and referral services, was established as a pilot project at the Pediatric Center of Excellence for HIV Care in Maharashtra. We designed the present study to compare management, compliance to ART, and mortality in children in the ART centers linked to the PCoE through telemedicine versus those that are not linked to the PCoE. Methods It was a retrospective cross-sectional study of secondary data from CLHAs from October 2013 through August 2015 in the ART centers to document the intermediate outcomes and to determine if the initiative has improved the quality of care for the CLHAs enrolled in the linked ART centers with nonlinked ART centers. The centers in which the telemedicine sessions were conducted regularly were called linked-regular centers and in whom it was conducted irregularly (less than the median of 12 videoconference cases), it was called a linked-irregular center. Data from 2803 children in 31 linked (1365 in irregular and 1438 in regular centers) and 2608 children in 28 nonlinked centers were analyzed. The outcomes in children in the pre-ART group (ART naïve) were (1) alive on pre-ART, (2) lost to follow-up on pre-ART, (3) death during the pre-ART period, (4) eligible but not initiated on ART, and (5) missing baseline and latest CD4 counts. The outcomes of children on ART were (1) alive on ART, (2) lost to follow-up on ART, (3) death on ART, and (4) missing baseline and latest CD4 counts. Results We found that a higher proportion of children in the linked-regular centers (79% vs. 70%, p < 0.001) and linked-irregular centers (76% vs. 70%, p = 0.04) was alive compared with that in the nonlinked centers in the pre-ART group. In this group, the proportion of children with missing baseline CD4 counts and latest CD4 counts was significantly low in linked (regular centers) centers. In the ART group, we found that a higher proportion of children in the linked-regular centers was alive compared with that in the linked-irregular centers (77% vs. 69%, p < 0.001); the proportion was not significantly different in nonlinked centers (77% vs. 78%, p = 0.56). In this group, the proportion of missing baseline CD4 counts was significantly lower in the linked-regular centers (3% vs 13%, p<0.001) and linked-irregular centers (1% vs. 13%, p < 0.001) compared with that in the nonlinked centers. Furthermore, the latest CD4 counts were missing in a significantly lower proportion of children in the linked-regular centers compared with those in the linked-irregular centers (6% vs. 18%, p < 0.001) and nonlinked centers (6% vs. 18%, p < 0.001). Conclusion Our study shows that the centers linked through telemedicine performed better in terms of patient care and treatment, with a lesser loss to follow-up and lesser deaths in CLHA. Overall, this pilot project of telemedicine for pediatric HIV has been proven to be acceptable, feasible, and effective in improving the quality of care for children living with HIV across the state of Maharashtra.

Time-varying age- and CD4-stratified rates of mortality and WHO stage 3 and stage 4 events in children, adolescents and youth 0 to 24 years living with perinatally acquired HIV, before and after antiretroviral therapy initiation in the paediatric IeDEA Global Cohort Consortium.

IntroductionEvaluating outcomes of paediatric patients with HIV provides crucial data for clinicians and policymakers. We analysed mortality and clinical events rates among children, adolescents, and youth with perinatally acquired HIV (PHIV) aged 0 to 24 years stratified by time‐varying age and CD4, before and after antiretroviral therapy (ART), in the paediatric IeDEA multiregional collaboration (East, West, Central and Southern Africa, Asia‐Pacific, and Central/South America and the Caribbean).MethodsART‐naïve children with HIV enrolled before age 10 (proxy for perinatal infection) at IeDEA sites between 2004 and 2016, with ≥1 CD4 measurement during follow‐up were included. We estimated incidence rates (IR) and 95% confidence intervals (95% CI) of mortality and first occurrence of WHO‐4 and WHO‐3 events, excluding tuberculosis, during person‐years (PY) spent within different age (<2, 2 to 4, 5 to 9, 10 to 14, 15 to 19, 20 to 24) and CD4 (percent when <5 years [<15%, 15% to 24%, ≥25%]; count when ≥5 years [<200, 200 to 499, ≥500 cells/µL]) strata. We used linear mixed models to predict CD4 evolution, with trends modelled by region.ResultsIn the pre‐ART period, 49 137 participants contributed 51 966 PY of follow‐up (median enrolment age: 3.9 years). The overall pre‐ART IRs were 2.8/100 PY (95% CI: 2.7 to 2.9) for mortality, 3.3/100 PY (95% CI: 3.0 to 3.5) for first occurrence of a WHO‐4 event, and 7.0/100 PY (95% CI: 6.7 to 7.4) for first occurrence of a WHO‐3 event. Lower CD4 and younger age strata were associated with increased rates of both mortality and first occurrence of a clinical event. In the post‐ART period, 52 147 PHIVY contributed 207 945 PY (ART initiation median age: 4.5 years). Overall mortality IR was 1.4/100 PY (95% CI: 1.4 to 1.5) and higher in low CD4 strata; patients at each end of the age spectrum (<2 and >19) had increased mortality post‐ART. IRs for first occurrence of WHO‐4 and WHO‐3 events were 1.3/100 PY (95% CI: 1.2 to 1.4) and 2.1/100 PY (95% CI: 2.0 to 2.2) respectively. These were also associated with lower CD4 and younger age strata.ConclusionsMortality and incidence of clinical events were highest in both younger (<2 years) and older (>19 years) youth with PHIV. Scaling‐up services for <2 years (early access to HIV diagnosis and care) and >19 years (adolescent‐ and youth‐focused health services) is critical to improve outcomes among PHIVY.

Assessing linear CD4 decline quantifying diagnosis delay after HIV seroconversion: assessing the linearity assumption of CD4 decline

PurposeTo estimate time from seroconversion to diagnosis, researchers have modeled time based on CD4 decline, assuming the square root of the CD4 count decreases linearly over time before antiretroviral treatment (ART) initiation. If true, utilizing CD4 counts reported anytime in the pre-ART period would result in estimates of diagnosis delay that are not appreciably different. MethodsWe applied CD4 depletion model parameters from seroconverter cohorts to New York City residents diagnosed from 2006 to 2015, having two or more pre-ART CD4 counts. ResultsMedian diagnosis delays based on first or second pre-ART CD4 counts were similar (n = 12,849; 2.8 years, interquartile range [IQR]: 0–7.7, and 2.8 years, IQR: 0–7.6, respectively; P = .09, Wilcoxon signed-rank test). Among people whose second pre-ART CD4 count was measured more than 6 months after diagnosis (n = 2761), the average diagnosis delay based on first pre-ART CD4 count was shorter (1.5 years, IQR: 0–5.4) than the second pre-ART CD4 count (1.7 years, IQR: 0–6.0) but not significantly (P = .12). ConclusionsResults are consistent with the linearity assumption of the CD4 depletion model. To estimate population-level diagnosis delay, researchers may use pre-ART CD4 counts reported more than 6 months post-diagnosis.

Abstract 182: Left Ventricular Diastolic Dysfunction in HIV-infected ART-naive and HIV-negative Tanzanian Adults: A Cross-sectional Study

Objective: To compare the prevalence and associated factors of left ventricular diastolic dysfunction in HIV-infected, ART naïve and HIV-negative Tanzanian adults. Methods: A cross-sectional analysis of a longitudinal study including: 257 HIV-infected, ART naïve adults and 265 HIV-negative controls. Echocardiography and traditional risk factors were performed and determined by standard investigations. The primary outcome was prevalence of left ventricular diastolic dysfunction. Secondary outcomes were factors associated with and grade of dysfunction. Results: Compared to HIV-negative controls, HIV-infected, ART naïve adults had a 2-fold higher prevalence of diastolic dysfunction (OR=2.06 [1.16-3.66], p=0.01). Additionally, age, female sex, obesity and hypertension were significantly associated with dysfunction in HIV-negative adults; whereas, only age and hypertension were associated with dysfunction in HIV-infected adults. As compared to HIV-negative controls, significantly more HIV-infected, ART naïve adults had higher grade dysfunction (p=0.02) and more ventricular hypertrophy. HIV-infected adults with diastolic dysfunction also expressed higher levels of inflammatory cytokines including TNFa, IL6, IL8, IL33 and sST2 as compared to both HIV-negative and HIV-infected adults without dysfunction. Conclusions: HIV-infected Tanzanian adults have a 2-fold higher prevalence of left ventricular diastolic dysfunction in the period immediately following diagnosis and before ART initiation as compared to HIV-negative adults, and this dysfunction is of higher grade and is associated with myocardial hypertrophy. These data identify diastolic dysfunction in an international cohort in the immediate post-diagnosis, pre-ART period similar to that previously reported in the post-ART period in high-income countries. Additionally, traditional cardiovascular risk factors are not significantly associated with dysfunction in HIV-infected adults; however, cytokine patterns are present and may be important for risk stratification in this group. Therefore, studies delineating appropriate screening for this population are needed.

Effect of ART scale-up and female migration intensity on risk of HIV acquisition: results from a population-based cohort in KwaZulu-Natal, South Africa

BackgroundDespite increased antiretroviral therapy (ART) coverage, the incidence of HIV infection among women in rural South Africa remains high. While many socio-demographic and behavioral factors have been identified, the effect of female migration intensity on the risk of HIV acquisition before and after ART scale-up has not been evaluated in the country.MethodsWe followed 13,315 female participants aged 15–49 who were HIV-uninfected at baseline and recorded their migration events between 2004 and 2015. Using a Cox proportional hazard model, we estimated the time to HIV acquisition among the women, adjusting for annual migration intensity (high: ≥2 events/year, moderate = 1 event/year, and low = 0 event/year) before and after ART scale-up in 2010.Results1998 (15%) new HIV-infection events were recorded during the observation period. Overall, high migration intensity was associated with an increased HIV acquisition risk among women when compared with low migration intensity (HR = 2.88, 95% CI: 1.56–5.53). Among those with high migration intensity, the risk of HIV acquisition was significantly lower in the post-ART period compared to the pre-ART period, after controlling for key socio-demographic and behavioural covariates (aHR = 0.18, 95% CI 0.04–0.83).ConclusionsWomen who migrated frequently after ART scale-up had a significantly reduced HIV acquisition risk compared to those before its implementation. While this reduction is encouraging, women who migrate frequently remain at high risk of HIV acquisition. In the era of ART, there remains a critical need for public health interventions to reduce the risk of HIV acquisition in this highly vulnerable population.

A Conceptual Framework to Reduce Inpatient Preventable Deaths

BackgroundEfforts to reduce preventable deaths in the in-hospital setting should target both cardiopulmonary arrest (CPA) prevention and optimal resuscitation. This requires consideration of a broad range of clinical issues and processes. A comprehensive, integrated system of care (SOC) that links data collection with a modular education program to reduce preventable deaths has not been defined. MethodsThis study was conducted in two urban university hospitals from 2005 to 2009. The Advanced Resuscitation Training (ART) program was implemented in 2007, incorporating hands-on resuscitative skills and in-hospital–specific training with an institutional resuscitation database. Linkage between the database and training modules occurs via the ART Matrix, which classifies all CPA events into the following etiologies: sepsis, hemorrhage, pulmonary embolus, heart failure, tachyarrhythmias, bradyarrhythmias, acute respiratory distress syndrome, non-intubated pulmonary disease, obstructive apnea, traumatic brain injury, ischemic brain injury, and intracranial mass lesions. This taxonomy was validated using descriptive statistics, before-and-after analysis evaluating CPA incidence, and multivariate logistic regression to predict CPA survival. ResultsA total of 336 inpatients suffered a cardiopulmonary arrest during the study period—187 in the pre-ART period and 149 in the post-ART period. The vast majority of CPA events were categorized using the ART Matrix with high inter-observer reliability. As anticipated, changes in CPA incidence and survival were observed for some Matrix categories but not others following ART implementation. In addition, multivariate logistic regression revealed strong independent associations between taxonomy classifications and outcome. ConclusionA novel SOC using a unique taxonomy for arrest classification appears to be effective at reducing inpatient CPA incidence and outcome.

Attrition among HIV positive children enrolled under integrated HIV care programme in Myanmar: 12 years cohort analysis

ABSTRACTBackground: In Myanmar, HIV seropositive children are being enrolled in an integrated HIV care (IHC) Program for HIV treatment and care since 2005.Objectives: To assess the: (a) attrition (death or loss-to-follow-up) rates among children (aged ≥ 18 months to < 15 years) enrolled into the programme before and after initiation of anti-retroviral therapy (ART) (pre-ART and ART periods); (b) demographic and clinical factors associated with attrition during these two periods.Methods: Children enrolled in IHC Programme and their status (death, lost to follow-up, regular follow-up or transferred out) was assessed as on 30 June 2017. Attrition rates (per 100 person-years) at pre – ART and ART periods were calculated and the association between demographic and clinical characteristics with attrition was assessed using Cox proportional hazards model.Results: Among 2,736 children enrolled, pre-ART attrition rate was 19 per 100 person-years of follow-up (95% CI: 17–21) and ART attrition rate was 4 per 100 person-years of follow-up (95% CI: 3–4) with higher levels during the initial few months of enrolment. The 36-month retention rates during pre-ART period was 75% (95% CI: 72–78) and during ART period was 87% (95% CI: 86–88). The children ‘at enrolment’ with relatively lower levels of haemoglobin, immune deficiency, underweight for age, higher WHO clinical stages, presence of hepatitis B infection had higher hazards of attrition in both periods.Conclusion: The attrition rates are high particularly among children with relatively poorer clinical, nutritional profiles at enrolment. The study suggests the urgent need for improving adherence counselling especially during the initial few months of enrolment and early ART initiation.

Factors Associated with Outcomes of Pre-ART HIV Care.

The World Health Organization recommended removing all CD4 requirements for initiation of antiretroviral therapy (ART) in resource-limited settings. We examined the pre-ART period to identify and assess factors associated with outcomes of pre-ART care. Four modes of transition out of pre-ART care were considered. Beta estimates from the competing risks Cox models were used to investigate whether the effects of covariates differed by mode of transition. Median CD4 counts at entry showed no meaningful change over time. Advanced disease progression and presence of opportunistic infections were significant predictors of pre-ART mortality. Men were more likely to die before initiating ART, transfer to another facility, or be lost to follow-up than were women. Removing CD4 thresholds is not likely to substantially reduce program mortality prior to ART initiation unless and until patients enroll earlier in disease progression. Care programs should focus on diagnosis and treatment of opportunistic infections to reduce pre-ART mortality.

Risk factors for mortality among malnourished HIV-infected adults eligible for antiretroviral therapy.

BackgroundA substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. We aimed to increase understanding of the factors affecting their high mortality, particularly in the high-risk period before ART initiation.MethodsWe analysed potential risk factors for mortality of Zambian and Tanzanian participants enrolled in the NUSTART clinical trial. Malnourished adults (n = 1815; body mass index [BMI] <18.5 kg/m2) were recruited at referral to ART and randomised to receive different nutritional supplements. Demographics, measures of body composition, blood electrolytes and clinical conditions were investigated as potential risk factors using Poisson regression models.ResultsThe mortality rate was higher in the period from referral to starting ART (121 deaths/100 person-years; 95 % CI 103, 142) than during the first 12 weeks of ART (66; 95 % CI 57, 76) and was not affected by trial study arm. In adjusted analyses, lower CD4 count, BMI and mid-arm circumference and raised C-reactive protein were associated with an increased risk of mortality throughout the study. Male sex and lower hand-grip strength carried an increased risk in the pre-ART period. Participants on tuberculosis treatment at referral had a lower mortality rate (adjusted Rate Ratio 0.44; 95 % CI 0.31, 0.63).ConclusionAmong malnourished ART-eligible adults, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events. Therefore, more efforts are needed to promote earlier diagnosis and immediate initiation of ART, as recently recommended by WHO for all persons with HIV worldwide. The positive effect of tuberculosis treatment suggests undiagnosed tuberculosis is a contributor to mortality in this population.Trial registrationPan African Clinical Trials Registry, PACTR201106000300631; registered on 1st June 2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1894-3) contains supplementary material, which is available to authorized users.

Retention and mortality outcomes from a community-supported public-private HIV treatment programme in Myanmar.

IntroductionThere is a growing interest in the potential contribution the private sector can make towards increasing access to antiretroviral therapy (ART) in low- and middle-income settings. This article describes a public–private partnership that was developed to expand HIV care capacity in Yangon, Myanmar. The partnership was between private sector general practitioners (GPs) and a community-based non-governmental organization (International HIV/AIDS Alliance).MethodsRetrospective analysis of 2119 patient records dating from March 2009 to April 2015 was conducted. Outcomes assessed were immunological response, loss to follow-up, all-cause mortality, and alive and retained in care. Follow-up time was calculated from the date of registration to the date of death, loss to follow-up, transfer out, or if still alive and known to be in care, until April 2015. Cox proportional hazards model was used to identify predictors of loss to follow-up and mortality. Kaplan–Meier survival analysis was used to estimate survival function of being alive and retained in care.ResultsThe median number of patients for each of the 16 GPs was 42 (interquartile range (IQR): 25–227), and the median follow-up period was 13 months. The median patient age was 35 years (IQR: 30–41); 56.6% were men, 62 and 11.8% were in WHO Stage III and Stage IV at registration, respectively; median CD4 count at registration was 177 cells/mm3; and 90.7% were on ART in April 2015. The median CD4 count at registration increased from 122 cells/mm3 in 2009 to 194 cells/mm3 in 2014. Among patients on ART, CD4 counts increased from a median of 187 cells/mm3 at registration to 436 cells/mm3 at 36 months. The median time to initiation of ART among eligible patients was 29 days, with 93.8% of eligible patients being initiated on ART within 90 days. Overall, 3.3% patients were lost to follow-up, 4.2% transferred out to other health facilities, and 8.3% died during the follow-up period. Crude mortality rate was 48.6/1000 person-years; 42% (n=74) of deaths occurred during the pre-ART period and 39.8% (n=70) occurred during the first six months of ART. Of those who died during the pre-ART period, 94.5% were eligible for ART. In multivariate regression, baseline CD4 count and ART status were independent predictors of mortality, whereas ART status, younger age and patient volumes per provider were predictors of loss to follow-up. Probability of being alive and retained in care at six months was 96.8% among those on ART, 38.5% among pre-ART but eligible patients, and 20.0% among ART-ineligible patients.ConclusionsEffectively supported private sector GPs successfully administered and monitored ART in Myanmar, suggesting that community-supported private sector partnerships can contribute to expansion of HIV treatment and care capacity. To further improve patient outcomes, early testing and initiation of ART, combined with close clinical monitoring and support during the initial periods of enrolling in treatment and care, are required.

Assisted reproductive technology use and outcomes among women with a history of cancer.

Assisted reproductive technology use and outcomes among women with a history of cancer.

Quantifying retention during pre-antiretroviral treatment in a large urban clinic in Uganda

BackgroundRetention studies are usually focused on patients on antiretroviral treatment (ART), however in Sub-Saharan Africa many patients get lost to program (LTP) in the pre-ART care period.. We investigated the proportion of patients not retained in care and factors associated with LTP (dead or lost to follow up ≥6 months) in the pre-ART care period.MethodsWe analyzed data from the Infectious Diseases Institute, Kampala, Uganda. We included all adult patients ≥18 years, ART naïve at program enrollment from 1st/Jan/2005. We described the number of patients not retained in care during the 3 steps of enrollment-to-treatment “cascade”: Step 1) From enrollment to CD4 count testing, Step 2) ART eligibility assessment. Patients were initially considered eligible if CD4 count was <200 cell/μL, and <350 cell/μL from 2012 onwards; Step 3) From eligibility to ART start. We described cumulative probability of being LTP by gender and ART eligibility using Kaplan Meier estimates. We used a Cox proportional hazards model to identify factors associated with being LTP at any stage for all patients and for those with a CD4 count available. Factors considered were age, gender, year of enrollment, and WHO stage.Results and discussionAfter enrollment in our program, cumulatively, a low proportion of patients (30.8 %) were retained and started on ART. The cumulative probability of being LTP was higher in males and patients not eligible for ART. In the multivariable Cox proportional Hazards model, male gender (HR: 1.19 CI 1.12-1.19) and clinical WHO stage 3 and 4 (HR: 1.20 CI 1.13-1.27) were associated with being LTP while older age was protective (HR: 0.98 0.96-0.99). Patients enrolled in the program more recently were also at lower risk of being LTP. In addition, among patients with CD4 count test, patients with higher CD4 count were at higher risk of being LTP.ConclusionsIn our program there has been suboptimal retention of patients in pre-ART care, particularly of patients not eligible for ART. Since the proportion of eligible patients has recently increased due to the higher recommended threshold for ART eligibility (CD4 count > 500 cell/μL in 2014), this could lead to an increase in program retention as more people fall under the recommended threshold and seek care.

Cancer incidence in people living with HIV/AIDS in Israel, 1981-2010.

Antiretroviral therapy (ART) improved the survival of people living with HIV/AIDS (PLWHA) and decreased HIV-related morbidities. This study assesses the cancer incidence of all adult PLWHA in Israel by transmission routes before and after 1996. This cohort study was based on cross-matching the National HIV/AIDS and Cancer Registries of all HIV/AIDS and cancer cases reported from 1981 to 2010 with the National civil census. PLWHA were followed-up until cancer diagnosis, death, leaving Israel, or 2010, whichever occurred first. Cancer incidence was adjusted for age, and compared with the National incidence. Of all 5,154 PLWHA followed-up for 36,296 person-years, 362 (7.0%) developed cancer (997.4 cases per 100,000 person-years). Higher hazard ratios to develop cancer were demonstrated among older PLWHA, Jewish people, and intravenous drug users. Cancer incidence among PLWHA was higher in the pre-ART period than after 1997 (1,232.0 and 846.7 cases per 100,000 person-years, respectively). The incidence of AIDS-defining cancers was higher than non-AIDS-defining malignancies, and higher in the pre-ART than the post-ART period (777.0 and 467.2 cases per 100,000 person-years, respectively), while the incidence of non-AIDS-defining cancers showed the opposite trend (376.5 and 455.0 cases per 100,000 person-years, respectively). The incidence of AIDS-defining and non-AIDS-defining cancers declined between the pre-ART and the post-ART period by 2.0 to 3.4 times. PLWHA had higher rates of malignancies than the general population. In conclusion, cancer incidence among PLWHA was associated with age, and declined after ART introduction; yet it was higher than that of the general population. PLWHA may benefit from age-related cancer screening, increased adherence to ART, and reduction of environmental oncogenes.

Determinants of Mortality and Loss to Follow-Up among Adults Enrolled in HIV Care Services in Rwanda

BackgroundAntiretroviral therapy (ART) improves morbidity and mortality in patients with HIV, however high rates of loss to follow-up (LTF) and mortality have been documented in HIV care and treatment programs.MethodsWe analyzed routinely-collected data on HIV-infected patients ≥15 years enrolled at 41 healthcare facilities in Rwanda from 2005 to 2010. LTF was defined as not attending clinic in the last 12 months for pre-ART patients and 6 months for ART patients. For the pre-ART period, sub-distribution hazards models were constructed to estimate LTF and death to account for competing risks. Kaplan-Meier (KM) and Cox proportional hazards models were used for patients on ART.Results31,033 ART-naïve adults were included, 64% were female and 75% were WHO stage I or II at enrollment. 17,569 (56%) patients initiated ART. Pre-ART competing risk estimates of LTF at 2 years was 11.2% (95%CI, 10.9–11.6%) and 2.9% for death (95%CI 2.7–3.1%). Among pre-ART patients, male gender was associated with higher LTF (adjusted sub-hazard ratio (aSHR) 1.3, 95%CI 1.1–1.5) and death (aSHR 1.7, 95%CI 1.4–2.1). Low CD4 count (CD4<100 vs. ≥350 aSHR 0.2, 95%CI 0.1–0.3) and higher WHO stage (WHO stage IV vs. stage I aSHR 0.4, 95%CI 0.2–0.6) were protective against pre-ART LTF. KM estimates for LTF and death in ART patients at 2 years were 4.4% (95%CI 4.4–4.5%) and 6.3% (95%CI 6.2–6.4%). In patients on ART, male gender was associated with LTF (adjusted hazard ratio (AHR) 1.4, 95%CI 1.2–1.7) and death (AHR1.3, 95%CI 1.2–1.5). Mortality was higher for ART patients ≥40 years and in those with lower CD4 count at ART initiation.ConclusionsLow rates of LTF and death were founds among pre-ART and ART patients in Rwanda but greater efforts are needed to retain patients in care prior to ART initiation, particularly among those who are healthy at enrollment.

Strengthening the HIV cascade to ensure an effective future ART response in sub-Saharan Africa

Timely linkage to antiretroviral therapy (ART) care is critical for reducing HIV-related morbidity, mortality and transmission. Studies investigating interventions to improve linkage to, and retention in, pre-ART care in sub-Saharan Africa were reviewed. Certain interventions used to overcome economic barriers for ART-patients (i.e. integration of services, medical and food incentives, intensified counselling and peer support) have also shown favourable results in the pre-ART period. A combined package of interventions found to be effective in the pre-ART and ART period might be effective for reducing attrition in both periods. Further operational research in this area is needed to identify local solutions.

Predictors of loss to follow-up before HIV treatment initiation in Northwest Ethiopia: a case control study

BackgroundIn Ethiopia, there is a growing concern about the increasing rates of loss to follow-up (LTFU) in HIV programs among people waiting to start HIV treatment. Unlike other African countries, there is little information about the factors associated with LTFU among pre-antiretroviral treatment (pre-ART) patients in Ethiopia. We conducted a case–control study to investigate factors associated with pre-ART LTFU in Ethiopia.MethodsCharts of HIV patients newly enrolled in HIV care at Gondar University Hospital (GUH) between September 11, 2008 and May 8, 2011 were reviewed. Patients who were “loss to follow-up” during the pre-ART period were considered to be cases and patients who were “in care” during the pre-ART period were controls. Logistic regression analysis was used to explore factors associated with pre-ART LTFU.ResultsIn multivariable analyses, the following factors were found to be independently associated with pre-ART LTFU: male gender [Adjusted Odds Ratio (AOR) = 2.00 (95% CI: 1.15, 3.46)], higher baseline CD4 cell count (251–300 cells/μl [AOR = 2.64 (95% CI: 1.05, 6.65)], 301–350 cells/μl [AOR = 5.21 (95% CI: 1.94, 13.99)], and >350 cells/μl [AOR = 12.10 (95% CI: 6.33, 23.12)] compared to CD4 cell count of ≤200 cells/μl) and less advanced disease stage (WHO stage I [AOR = 2.81 (95% CI: 1.15, 6.91)] compared to WHO stage IV). Married patients [AOR = 0.39 (95% CI: 0.19, 0.79)] had reduced odds of being LTFU. In addition, patients whose next visit date was not documented on their medical chart [AOR = 241.39 (95% CI: 119.90, 485.97)] were more likely to be LTFU.ConclusionOur study identified various factors associated with pre-ART LTFU. The findings highlight the importance of giving considerable attention to pre-ART patients’ care from the time that they learn of their positive HIV serostatus. The completeness of the medical records, the standard of record keeping and obstacles to retrieving charts also indicate a serious problem that needs due attention from clinicians and data personnel.

Assessment of incidence and predictors of pregnancy among patients on antiretroviral therapy (ART) and pre-ART: a retrospective cohort study

BackgroundHIV care and treatment services are in a unique position to address the childbearing desires of HIV-infected individuals as well as to ensure safe pregnancy and delivery. However, in Ethiopia incidence and predictors of pregnancy among pre-antiretroviral therapy (pre-ART) and on-ART women are not addressed despite the programme's importance. The study's objective is to assess the incidence and predictors of pregnancy among pre-ART and on-ART women in health facilities of Kolfe Keranio subcity of Addis Ababa, Ethiopia, in 2011. MethodsIn health facilities of Kolfe Keranio, a retrospective follow-up study from 2006 to 2011 was conducted. A total of 661 women's charts were selected by simple random sampling and reviewed. Data were cleared, checked, and entered by Epi Info version 3.5.1 and analysed by SPSS version 16. Descriptive statistics and incidence rate of pregnancy in person-years of follow-up are reported. A life table was used to estimate the probabilities of becoming pregnant. The Cox proportional hazards model was used, and results are expressed as hazard ratios with 95% CIs. FindingsThe incidence of pregnancy among women who enrolled in HIV care and treatment programmes is 6·5 per 100 person-years. This total is comprised of 21 incident pregnancies with the rate of 3·9 per 100 person-years in the pre-ART period and 67 incident pregnancies with the rate of 8·02 per 100 person years in the ART period. There is also significant difference in the pregnancy experience between the ART period and pre-ART period predictors of pregnancy in HIV-infected women who have one to four children, adjusted hazard ratio (AHR) 0·185 (95% CI 0·09–0·99); use of non-barrier contraception methods, AHR 0·54 (0·32–0·90); being in WHO stage 2, AHR 2·7 (1·50–4·99); current CD4 at least 500 cells per μl, AHR 4·5 (2·29–5·89); and ART use, AHR 2·7 (1·5–4·99). InterpretationThe incidence of pregnancy in women who are on ART is increasing, highlighting the urgent need to make pregnancy-related services a central component of HIV care and ART programmes. FundingUniversity of Gondar, Ethiopia.

Failure to Initiate Antiretroviral Therapy, Loss to Follow-up and Mortality Among HIV-Infected Patients During the Pre-ART Period in Uganda

Delays and failures in initiation of antiretroviral therapy (ART) among treatment eligible patients may compromise the effectiveness of HIV care in Africa. An accurate understanding, however, of the pace and completeness of ART initiation and mortality during the waiting period is obscured by frequent losses to follow-up. We evaluated newly ART-eligible HIV-infected adults from 2007 to 2011 in a prototypical clinic in Mbarara, Uganda. A random sample of patients lost to follow-up was tracked in the community to determine vital status and ART initiation after leaving the original clinic. Outcomes among the tracked patients were incorporated using probability weights, and a competing risks approach was used in analyses. Among 2633 ART-eligible patients, 490 were lost to follow-up, of whom a random sample of 132 was tracked and 111 (84.0%) had outcomes ascertained. After incorporating the outcomes among the lost, the cumulative incidence of ART initiation at 30, 90, and 365 days after eligibility was 16.0% [95% confidence interval (CI): 14.2 to 17.7], 64.5% (95% CI: 60.9 to 68.1), and 81.7% (95% CI: 77.7 to 85.6). Death before ART was 7.7% at 1 year. Male sex, higher CD4 count, and no education were associated with delayed ART initiation. Lower CD4 level, malnourishment, and travel time to clinic were associated with mortality. Using a sampling-based approach to account for losses to follow-up revealed that both the speed and the completeness of ART initiation were suboptimal in a prototypical large clinic in Uganda. Improving the kinetics of ART initiation in Africa is needed to make ART more in real-world populations.

Rates and Cost of Hospitalization Before and After Initiation of Antiretroviral Therapy in Urban and Rural Settings in South Africa

Few studies have compared hospitalizations before and after antiretroviral therapy (ART) initiation in the same patients. We analyzed the cost of hospitalizations among 3906 adult patients in 2 South African hospitals, 30% of whom initiated ART. Hospitalizations were 50% and 40% more frequent and 1.5 and 2.6 times more costly at a CD4 cell count, 100 cells/mm(3) when compared with 200–350 cells/mm(3) in the pre-ART and ART period, respectively. Mean inpatient cost per patient year was USD 117 (95%confidence interval, 85 to 158) for patients on ART and USD 72(95% confidence interval, 56 to 89) for pre-ART patients. Raising ART eligibility thresholds could avoid the high cost of hospitalization before and immediately after ART initiation.