Ray W. Shiraishi

Four-Year Treatment Outcomes of Adult Patients Enrolled in Mozambique's Rapidly Expanding Antiretroviral Therapy Program

Background In Mozambique during 2004–2007 numbers of adult patients (≥15 years old) enrolled on antiretroviral therapy (ART) increased about 16-fold, from <5,000 to 79,500. All ART patients were eligible for co-trimoxazole. ART program outcomes, and determinants of outcomes, have not yet been reported. Methodology/Principal Findings In a retrospective cohort study, we investigated rates of mortality, attrition (death, loss to follow-up, or treatment cessation), immunologic treatment failure, and regimen-switch, as well as determinants of selected outcomes, among a nationally representative sample of 2,596 adults initiating ART during 2004–2007. At ART initiation, median age of patients was 34 and 62% were female. Malnutrition and advanced disease were common; 18% of patients weighed <45 kilograms, and 15% were WHO stage IV. Median baseline CD4+ T-cell count was 153/µL and was lower for males than females (139/µL vs. 159/µL, p<0.01). Stavudine, lamivudine, and nevirapine or efavirenz were prescribed to 88% of patients; only 31% were prescribed co-trimoxazole. Mortality and attrition rates were 3.4 deaths and 19.8 attritions per 100 patient-years overall, and 12.9 deaths and 57.2 attritions per 100 patient-years in the first 90 days. Predictors of attrition included male sex [adjusted hazard ratio (AHR) 1.5; 95% confidence interval (CI), 1.3–1.8], weight <45 kg (AHR 2.1; 95% CI, 1.6–2.9, reference group >60 kg), WHO stage IV (AHR 1.7; 95% CI, 1.3–2.4, reference group WHO stage I/II), lack of co-trimoxazole prescription (AHR 1.4; 95% CI, 1.0–1.8), and later calendar year of ART initiation (AHR 1.5; 95% CI, 1.2–1.8). Rates of immunologic treatment failure and regimen-switch were 14.0 and 0.6 events per 100-patient years, respectively. Conclusions ART initiation at earlier disease stages and scale-up of co-trimoxazole among ART patients could improve outcomes. Research to determine reasons for low regimen-switch rates and increasing rates of attrition during program expansion is needed.

Knowledge of HIV status, sexual risk behaviors and contraceptive need among people living with HIV in Kenya and Malawi.

Background:Several studies support the need for effective interventions to reduce HIV transmission risk behaviors among people living with HIV/AIDS (PLWHAs). Design:Cross-sectional nationally representative demographic health survey of Kenya (2003) and Malawi (2004–2005) that included HIV testing for consenting adults. Methods:We analyzed demographic health survey data for awareness of HIV status and sexual behaviors of PLWHAs (Kenya: 412; Malawi: 664). The analysis was adjusted (weighted) for the design of the survey and the results are nationally representative. Findings:Eighty-four percent of PLWHAs in Kenya and 86% in Malawi had sex in the past 12 months and in each country, 10% reported using condoms at last intercourse. Among sexually active PLWHAs, 86% in Kenya and 96% in Malawi reported their spouse or cohabiting partner as their most recent partner. In multivariate logistic regression models, married or cohabiting PLWHAs were significantly more likely to be sexually active and less likely to use condoms. Over 80% of PLWHAs were unaware of their HIV status. Of HIV-infected women, nearly three-quarters did not want more children either within the next 2 years or ever, but 32% in Kenya and 20% in Malawi were using contraception. Interpretation:In 2003–2005, majority of PLWHAs in Kenya and Malawi were unaware of their HIV status and were sexually active, especially married or cohabiting PLWHAs. Of HIV-infected women not wanting more children, few used contraception. HIV testing should be expanded, prevention programs should target married or cohabiting couples and family planning services should be integrated with HIV services.

A public health approach to rapid scale-up of antiretroviral treatment in Malawi during 2004-2006.

Background:Approximately 1 million people are infected with HIV in Malawi, where AIDS is the leading cause of death in adults. By December 31, 2007, more than 141,000 patients were initiated on antiretroviral treatment (ART) by use of a public health approach to scale up HIV services. Methods:We analyzed national quarterly and longitudinal cohort data from October 2004 to December 2006 to examine trends in characteristics of patients initiating ART, end-of-quarter clinical outcomes, and 6- and 12-month survival probability. Findings:During a 27-month period, 72,666 patients were initiated on ART, of whom about two-thirds were women. The percentage of patients initiated on ART who were children and farmers increased from 5.5% to 9.0% and 23% to 32%, respectively (P < 0.001 for trends). Estimated survival probability ranged from 85% to 88% at 6 months and 81% to 84% at 12 months on ART. Interpretation:In Malawi, a public health approach to ART increased treatment access and maintained high 6- and 12-month survival. Resource-limited countries scaling up ART programs may benefit from this approach of simplified clinical decision making, standardized ART regimens, nonphysician care, limited laboratory support, and centralized monitoring and evaluation.

Lack of knowledge of HIV status a major barrier to HIV prevention, care and treatment efforts in Kenya: results from a nationally representative study.

Background We analyzed HIV testing rates, prevalence of undiagnosed HIV, and predictors of testing in the Kenya AIDS Indicator Survey (KAIS) 2007. Methods KAIS was a nationally representative sero-survey that included demographic and behavioral indicators and testing for HIV, HSV-2, syphilis, and CD4 cell counts in the population aged 15–64 years. We used gender-specific multivariable regression models to identify factors independently associated with HIV testing in sexually active persons. Results Of 19,840 eligible persons, 80% consented to interviews and blood specimen collection. National HIV prevalence was 7.1% (95% CI 6.5–7.7). Among ever sexually active persons, 27.4% (95% CI 25.6–29.2) of men and 44.2% (95% CI 42.5–46.0) of women reported previous HIV testing. Among HIV-infected persons, 83.6% (95% CI 76.2–91.0) were unaware of their HIV infection. Among sexually active women aged 15–49 years, 48.7% (95% CI 46.8–50.6) had their last HIV test during antenatal care (ANC). In multivariable analyses, the adjusted odds ratio (AOR) for ever HIV testing in women ≥35 versus 15–19 years was 0.2 (95% CI: 0.1–0.3; p<0.0001). Other independent associations with ever HIV testing included urban residence (AOR 1.6, 95% CI: 1.2–2.0; p = 0.0005, women only), highest wealth index versus the four lower quintiles combined (AOR 1.8, 95% CI: 1.3–2.5; p = 0.0006, men only), and an increasing testing trend with higher levels of education. Missed opportunities for testing were identified during general or pregnancy-specific contacts with health facilities; 89% of adults said they would participate in home-based HIV testing. Conclusions The vast majority of HIV-infected persons in Kenya are unaware of their HIV status, posing a major barrier to HIV prevention, care and treatment efforts. New approaches to HIV testing provision and education, including home-based testing, may increase coverage. Targeted interventions should involve sexually active men, sexually active women without access to ANC, and rural and disadvantaged populations.

Patient Retention, Clinical Outcomes and Attrition-Associated Factors of HIV-Infected Patients Enrolled in Zimbabwe's National Antiretroviral Therapy Programme, 2007???2010

Background Since establishment of Zimbabwes National Antiretroviral Therapy (ART) Programme in 2004, ART provision has expanded from <5,000 to 369,431 adults by 2011. However, patient outcomes are unexplored. Objective To determine improvement in health status, retention and factors associated with attrition among HIV-infected patients on ART. Methods A retrospective review of abstracted patient records of adults ≥15 years who initiated ART from 2007 to 2009 was done. Frequencies and medians were calculated for rates of retention in care and changes in key health status outcomes at 6, 12, 24 and 36 months respectively. Cox proportional hazards models were used to determine factors associated with attrition. Results Of the 3,919 patients, 64% were female, 86% were either WHO clinical stage III or IV. Rates of patient retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. After ART initiation, median weight gains at 6, 12, and 24 months were 3, 4.5, and 5.0 kgs whilst median CD4+ cell count gains at 6, 12 and 24 months were 122, 157 and 279 cells/µL respectively. Factors associated with an increased risk of attrition included male gender (AHR 1.2; 95% CI, 1.1–1.4), baseline WHO stage IV (AHR 1.7; 95% CI, 1.1–2.6), lower baseline body weight (AHR 2.0; 95% CI, 1.4–2. 8) and accessing care from higher level healthcare facilities (AHR 3.5; 95% 1.1–11.2). Conclusions Our findings with regard to retention as well as clinical and immunological improvements following uptake of ART, are similar to what has been found in other settings. Factors influencing attrition also mirror those found in other parts of sub-Saharan Africa. These findings suggest the need to strengthen earlier diagnosis and treatment to further improve treatment outcomes. Whilst decentralisation improves ART coverage it should be coupled with strategies aimed at improving patient retention.

Reduced risk of transfusion‐transmitted HIV in Kenya through centrally co‐ordinated blood centres, stringent donor selection and effective p24 antigen‐HIV antibody screening

Background  Following a 1994 study showing a high rate of transfusion‐associated HIV, Kenya implemented WHO blood safety recommendations including: organizing the Kenya National Blood Transfusion Service (NBTS), stringent blood donor selection, and universal screening with fourth‐generation p24 antigen and HIV antibody assays. Here, we estimate the risk of transfusion‐associated HIV transmission in Kenya resulting from NBTS laboratory error and consider the potential safety benefit of instituting pooled nucleic acid testing (NAT) to reduce window period transmission.

Outcomes of antiretroviral therapy in Vietnam: results from a national evaluation.

Objectives Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam’s national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations. Design Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART. Methods Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data. Results Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4–76.5, median age 30, interquartile range [IQR]: 26–34, 62.0% reported a history of intravenous drug use, CI: 58.6–65.3). Median baseline CD4 cell count was 78 cells/mm3 (IQR: 30–162) and 30.4% (CI: 25.8–35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8–89.9), 84.0% (CI: 81.8–86.0), 78.8% (CI: 75.7–81.6), and 74.6% (CI: 69.6–79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45–153), 142 (IQR: 78–217), 213 (IQR: 120–329), and 254 (IQR: 135–391) cells/mm3. Patients who were PWID showed significantly poorer retention. Conclusions The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.

Routine data from prevention of mother-to-child transmission (PMTCT) HIV testing not yet ready for HIV surveillance in Mozambique: a retrospective analysis of matched test results

BackgroundOpt-out HIV testing is offered at 70% of antenatal care (ANC) clinics in Mozambique through the prevention of mother-to-child transmission (PMTCT) program. If routine data from this program were of sufficient quality, their heightened coverage and continuous availability could complement or even replace biannual sentinel serosurveys that currently serve as the primary HIV surveillance system in Mozambique.MethodsWe assessed the efficacy of routine HIV testing data from prevention of mother-to-child transmission programs for estimating the prevalence of HIV infection among pregnant women. The PMTCT program uses sequential point-of-care rapid tests conducted on site while ANC surveillance surveys use dried blood spots tested sequentially for HIV-1/2 antibodies at a central laboratory. We compared matched routine PMTCT and ANC surveillance test results collected during 2007 and 2009 ANC surveillance surveys from 36 sentinel sites.ResultsAfter excluding 659 women without PMTCT data, including 83 who refused rapid testing, test results from a total of 20,563 women were available. Pooling the data from both years indicated HIV prevalence from routine PMTCT testing was 14.4% versus 15.2% from surveillance testing (relative difference -5.1%; absolute difference -0.78%). Positive percent agreement (PPA) of PMTCT versus surveillance tests was 88.5% (95% Confidence Interval [CI]: 85.7-91.3%), with 19 sites having PPA below 90%; Negative percent agreement (NPA) was 98.9% (CI: 98.5-99.2%). No significant difference was found among three regions (North, Center and South), however both PPA and NPA were significantly higher in 2009 than 2007 (p < 0.05).ConclusionsWe found low PPA of PMTCT test results compared to surveillance data which is indicative either of testing errors or data reporting problems. Nonetheless, PPA improved significantly from 2007 to 2009, a possible positive trend that should be investigated further. Although use of PMTCT test results would not dramatically change HIV prevalence estimates among pregnant women, the impact of site-level differences on surveillance models should be evaluated before these data are used to replace or complement ANC surveillance surveys.

Lower levels of antiretroviral therapy enrollment among men with HIV compared with women - 12 countries, 2002-2013

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. Presidents Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(†) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.

Incidence and determinants of tuberculosis among adults initiating antiretroviral therapy--Mozambique, 2004-2008.

Background In Mozambique, tuberculosis (TB) is thought to be the most common cause of death among antiretroviral therapy (ART) enrollees. Monitoring proportions of enrollees screened for TB, and incidence and determinants of TB during ART can help clinicians and program managers identify program improvement opportunities. Methodology/Principal Findings We conducted a retrospective cohort study among a nationally representative sample of the 79,500 adults (>14 years old) initiating ART during 2004–2007 to estimate clinician compliance with TB screening guidelines, factors associated with active TB at ART initiation, and incidence and predictors of documented TB during ART follow-up. Of 94 sites enrolling >50 adults on ART, 30 were selected using probability-proportional-to-size sampling; 2,596 medical records at these sites were randomly selected for abstraction and analysis. At ART initiation, median age of patients was 34, 62% were female, median baseline CD4+ T-cell count was 153/µL, and 11% were taking TB treatment. Proportions of records with TB screening documentation before ART initiation improved from 31% to 66% during 2004–2007 (p<0.001). TB screening compliance varied widely by ART clinic [n = 30, 2%–98% (p<0.001)] and supporting non-Governmental Organization (NGO) [n = 7, 27%–83% (p<0.001)]. Receiving TB treatment at ART enrollment was associated with male sex (p<0.001), weight <45 kg (p<0.001) and CD4<50/µL (p = 0.001). Isoniazid preventive therapy (IPT) was prescribed to <1% of ART enrollees not taking TB treatment. TB incidence during ART was 2.32 cases per 100 person-years. Factors associated with TB incidence included adherence to ART <95% (AHR 2.06; 95% CI, 1.32–3.21). Conclusion Variations in TB screening by clinic and NGO may reflect differing investments in TB screening activities. Future scale-up should target under-performing clinics. Scale-up of TB screening at ART initiation, IPT, and ART adherence interventions could significantly reduce incident TB during ART.