Site-Level Comprehensiveness of Care Is Associated with Individual Clinical Retention Among Adults Living with HIV in International Epidemiology Databases to Evaluate AIDS, a Global HIV Cohort Collaboration, 2000-2016.

Retention in care (RIC) reduces HIV transmission and associated morbidity and mortality. We examined whether delivery of comprehensive services influenced individual RIC within the International epidemiology Databases to Evaluate AIDS (IeDEA) network. We collected site data through IeDEA assessments 1.0 (2000-2009) and 2.0 (2010-2016). Each site received a comprehensiveness score for service availability (1 = present, 0 = absent), with tallies ranging from 0 to 7. We obtained individual-level cohort data for adults with at least one visit from 2000 to 2016 at sites responding to either assessment. Person-time was recorded annually, with RIC defined as completing two visits at least 90 days apart in each calendar year. Multivariable modified Poisson regression clustered by site yielded risk ratios and predicted probabilities for individual RIC by comprehensiveness. Among 347,060 individuals in care at 122 sites with 1,619,558 person-years of follow-up, 69.8% of person-time was retained in care, varying by region from 53.8% (Asia-Pacific) to 82.7% (East Africa); RIC improved by about 2% per year from 2000 to 2016 (p = 0.012). Every site provided CD4+ count testing, and >90% of individuals received care at sites that provided combination antiretroviral therapy adherence measures, prevention of mother-to-child transmission, tuberculosis screening, HIV-related prevention, and community tracing services. In adjusted models, individuals at sites with more comprehensive services had higher probabilities of RIC (0.71, 0.74, and 0.83 for scores 5, 6, and 7, respectively; p = 0.019). Within IeDEA, greater site-level comprehensiveness of services was associated with improved individual RIC. Much work remains in exploring this relationship, which may inform HIV clinical practice and health systems planning.

Aging with HIV: what effect on mortality and loss to follow-up in the course of antiretroviral therapy? The IeDEA West Africa Cohort Collaboration.

BACKGROUND: Reporting mortality and lost to follow-up (LTFU) by age is essential as older HIV-positive patients might be at risk of long-term effects of living with HIV and/or taking antiretroviral therapy (ART). As age effects might not be linear and might impact HIV outcomes in the oldest more severely, people living with HIV (PLHIV) aged 50-59 years and PLHIV aged >60 years were considered separately. SETTING: Seventeen adult HIV/AIDS clinics spread over nine countries in West Africa. METHODS: Data were collected within the International Epidemiological Databases to Evaluate AIDS West Africa Collaboration. ART-naïve PLHIV-1 adults aged >16 years initiating ART and attending ≥2 clinic visits were included (N=73,525). Age was divided into five groups: 16-29/30-39/40-49/50-59/≥60 years. The age effect on mortality and LTFU was evaluated with Kaplan-Meier curves and multivariable Cox proportional hazard regressions. RESULTS: At month 36, 5.9% of the patients had died and 47.3% were LTFU. Patients aged ≥60 (N=1,736) and between 50-59 years old (N=6,792) had an increased risk of death in the first 36 months on ART (adjusted hazard ratio=1.66; 95% CI: 1.36-2.03 and adjusted hazard ratio=1.31; 95% CI: 1.15-1.49, respectively; reference: <30 years old). Patients ≥60 years old tend to be more often LTFU. CONCLUSION: The oldest PLHIV presented the poorest outcomes, suggesting that the PLHIV aged >50 years old should not be considered as a unique group irrespective of their age. Tailored programs focusing on improving the care services for older PLHIV in Sub-Saharan Africa are clearly needed to improve basic program outcomes.

Twenty-Year Evolution of Hepatitis B Virus and Human Immunodeficiency Virus Prevalence and Incidence in Voluntary Blood Donors in Côte d'Ivoire.

BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common risk factors. The parallel description of their frequency over time may help capture their similarities and differences. METHODS: Using data from the National Transfusion Center of Abidjan, we estimated the following over a 20-year period: (1) the prevalence of HIV and hepatitis B surface antigen (HBsAg) positivity at first contact; and (2) the incidence of HIV and HBsAg seroconversion in negative first-time blood donors. RESULTS: Between 1992 and 2012, 422319 donors (men [M] = 74%) provided 1063825 blood donations. For first-time donors, HIV prevalence decreased from 7.1% (M = 5.9%, women [W] =11.0%) in 1992-1994 to 1.1% (M = 0.8%, W = 2.0%) in 2010-2012. Prevalence of HBsAg positivity remained stable at 10.8% (M = 11.7%, W = 7.3%) in 1992-1994 to 11.1% (M = 12.5%, W = 7.1%) in 2010-2012. Among regular donors (N = 129256), the incidence of becoming HIV or HBsAg positive, respectively, decreased from 4.9 per 100 (M = 4.5, W = 8.6) and 7.3 per 100 person-years (M = 7.8, W = 2.3) in 1992-1994 to 0.07 (M = 0.06, W = 0.11) and 0.2 per 100 person-years (M = 0.2, W = 0.2) in 2010-2012. CONCLUSIONS: Human immunodeficiency virus prevalence and incidence decreased dramatically over time, whereas HBV prevalence remained stable. Incidence of HBsAg seroconversion, although decreasing, still reached unexpected levels, suggesting that the risk of HBV infection in adults may be higher than expected. Hepatitis B surface antigen-negative blood-donors should be offered HBV vaccination.

Severe morbidity after antiretroviral (ART) initiation: active surveillance in HIV care programs, the IeDEA West Africa collaboration.

BACKGROUND: The causes of severe morbidity in health facilities implementing Antiretroviral Treatment (ART) programmes are poorly documented in sub-Saharan Africa. We aimed to describe severe morbidity among HIV-infected patients after ART initiation, based on data from an active surveillance system established within a network of specialized care facilities in West African cities. METHODS: Within the International epidemiological Database to Evaluate AIDS (IeDEA)--West Africa collaboration, we conducted a prospective, multicenter data collection that involved two facilities in Abidjan, Côte d'Ivoire and one in Cotonou, Benin. Among HIV-infected adults receiving ART, events were recorded using a standardized form. A simple case-definition of severe morbidity (death, hospitalization, fever>38°5C, Karnofsky index<70%) was used at any patient contact point. Then a physician confirmed and classified the event as WHO stage 3 or 4 according to the WHO clinical classification or as degree 3 or 4 of the ANRS scale. RESULTS: From December 2009 to December 2011, 978 adults (71% women, median age 39 years) presented with 1449 severe events. The main diagnoses were: non-AIDS-defining infections (33%), AIDS-defining illnesses (33%), suspected adverse drug reactions (7%), other illnesses (4%) and syndromic diagnoses (16%). The most common specific diagnoses were: malaria (25%), pneumonia (13%) and tuberculosis (8%). The diagnoses were reported as syndromic in one out of five events recorded during this study. CONCLUSIONS: This study highlights the ongoing importance of conventional infectious diseases among severe morbid events occurring in patients on ART in ambulatory HIV care facilities in West Africa. Meanwhile, additional studies are needed due to the undiagnosed aspect of severe morbidity in substantial proportion.

Incidence of serious morbidity in HIV-infected adults on antiretroviral therapy in a West African care centre, 2003-2008.

BACKGROUND: In resource-limited settings, scaling-up antiretroviral treatment (ART) has required the involvement of decentralized health facilities with limited equipment. We estimated the incidence of serious morbidity among HIV-infected adults receiving ART in one of these HIV routine care center in sub-Saharan Africa. METHODS: We conducted a prospective study at the Centre Medical de Suivi des Donneurs de Sang (CMSDS), which is affiliated with the National Centre for Blood Transfusion in Abidjan, Côte d'Ivoire. Adult patients infected with HIV-1 or HIV-1/HIV-2 who initiated ART between January 2003 and December 2008 were eligible for the study. Standardized clinical data were collected at each visit. Serious morbidity was defined as a new episode of malaria, WHO stage 3-4 event, ANRS grade 3-4 adverse event, or any event leading to death or to hospitalization. RESULTS: 1008 adults, 67% women, with a median age of 35 years, and a median pre-ART CD4 count of 186/mm3 started ART and were followed for a median of 17.3 months. The overall incidences of loss to follow-up, death, and attrition were 6.2/100 person-years (PY) [95% CI 5.1-7.2], 2.3/100 PY [95% CI 1.6-2.9], and 8.1/100 PY [95% CI 7.0-9.4], respectively. The incidence of first serious event was 11.5/100 PY overall, 15.9/100 PY within the first year and 8.3/100 PY thereafter. The most frequently documented specific diagnoses were malaria, tuberculosis, bacterial septicemia and bacterial pneumonia. CONCLUSION: Among HIV-infected adults followed in routine conditions in a West African primary care clinic, we recorded a high incidence of serious morbidity during the first year on ART. Providing care centers with diagnostic tools and standardizing data collection are necessary steps to improve the quality of care in primary care facilities in sub-Saharan Africa.

AIDS and non-AIDS morbidity and mortality across the spectrum of CD4 cell counts in HIV-infected adults before starting antiretroviral therapy in Cote d'Ivoire.

BACKGROUND: In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count-specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)-infected adults with high CD4 cell counts. In sub-Saharan Africa, these CD4 cell count-specific estimates are scarce. METHODS: From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d'Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200 cells/µL once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count-specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. RESULTS: Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ≥650, 500-649, 350-499, 200-349, 100-199, 50-99, and 0-49 cells/µL CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ≥200 CD4 cells/µL, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200-349 and ≥650 cells/µL, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). CONCLUSIONS: Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ≥200 cells/µL. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub-Saharan Africa.

Short communication: Severe symptomatic hyperlactatemia among HIV type 1-infected adults on antiretroviral therapy in Côte d'Ivoire.

Stavudine is no longer recommended for use in first-line antiretroviral therapy (ART), but it remains in high demand worldwide because it is affordable. We report the clinical presentation and incidence of severe hyperlactatemia (SL) in HIV-infected adults who initiated ART between April 2005 and May 2009 in Côte d'Ivoire, West Africa. In a prospective cohort study at the HIV care center affiliated with the National Centre for Blood Transfusion, we used standardized forms to record baseline and follow-up data. We measured serum lactate levels for all adults on ART who showed signs of hyperlactatemia. SL was defined as serum lactate >2.5 mmol/liter. Overall, 806 adults initiated ART. Among the 591 patients (73%) on stavudine-containing regimens, 394 were women (67%); the median pre-ART CD4 count was 150/mm3 and the median body mass index was 20.9 kg/m2. These patients were followed for a median of 28 months. We detected SL only among patients taking stavudine. The incidence of SL was 0.55/100 person-years (PY) (95% CI 0.47-0.63) overall and 0.85/100 PY among women (95% CI 0.75-0.95). Among the eight patients with SL, 100% lost >9% of body weight before diagnosis, 100% had serum lactate >4 mmol/liter (range 4.2-12.1), 50% had pre-ART BMI >25 kg/m2, and three patients died (38%), accounting for 6.4% of deaths among patients taking stavudine. As long as HIV clinicians continue to use stavudine in sub-Saharan Africa, they should watch out for acute unexplained weight loss in patients taking ART, particularly among women and patients with high pre-ART BMI.

Risk behaviors in volunteer blood donors who seroconverted for HIV, Abidjan, Côte d'Ivoire 1997 to 2005.

BACKGROUND: The residual risk of human immunodeficiency virus (HIV) transmission from blood products in the Abidjan National Blood Transfusion Center was estimated to be 1 in 5780 blood donations over the period 2002 through 2004. We aimed at describing risk behaviors in blood donors who seroconverted for HIV in Abidjan to improve the pre-blood donation selection. STUDY DESIGN AND METHODS: We investigated the behavioral profile of HIV seroconverters assessed before their HIV diagnosis, during the blood donation selection at the blood bank of Abidjan, and compared it to the profile documented after this HIV diagnosis, at enrollment in the PRIMO-CI cohort. Since 1997, enrollment in this cohort is offered to every blood donor whose delay since HIV seroconversion was 36 months or less. RESULTS: Among the 418 blood donors who seroconverted for HIV between 1997 and 2005, 241 were enrolled in the cohort. Median age was 28 years and 63% were men. The median time between the last HIV-negative test and the first positive test was 7 months. Since the last blood donation, 29% of donors reported unprotected sexual intercourse with multiple casual sexual partners, 55% unprotected sexual intercourse with one casual sexual partner, and 36% sharing of nail clippers. During the pre-blood donation questionnaire, 69% of HIV seroconverters had reported unprotected sexual intercourse since the last blood donation (vs. 89% reported after donation), and 7% had had multiple casual sexual partners (vs. 32%). CONCLUSION: Volunteer blood donors who seroconverted for HIV in Abidjan reported a high proportion of unprotected sexual intercourse with casual sexual partners.

HIV-1 DNA in peripheral blood mononuclear cells is strongly associated with HIV-1 disease progression in recently infected West African adults.

OBJECTIVE: To analyze the association between the HIV-1 DNA level in peripheral blood mononuclear cells (PBMCs) and disease progression in recently infected West African adults. METHODS: HIV-1 DNA levels were measured in the PBMCs of 200 adults in the French National Agency for Research on AIDS and viral Hepatitis (ANRS) 1220 cohort who had recently been infected with HIV-1. The association between baseline HIV-1 DNA levels and disease progression was analyzed using multivariate Cox regression. Disease progression was defined as the occurrence of any of the following outcomes: death, first World Health Organization stage 3-4 event, or CD4 count<200/mm. RESULTS: About 200 participants were followed for a median of 30 months. At baseline, the median time from HIV-1 seroconversion was 9 months, median CD4 T-cell count was 471/mm, median HIV-1 DNA level was 3.0 log10 copies/10 PBMCs, and median plasma HIV-1 RNA level was 4.6 log10 copies/mL. The 5-year probability of remaining free of any outcome was 0.74 [95% confidence interval (CI): 0.61 to 0.83] and 0.36 (95% CI: 0.23 to 0.49) in patients with baseline HIV-1 DNA3.0 log10 copies/10 PBMCs, respectively (P<0.001). The adjusted hazard ratio of disease progression was 2.17 in patients with HIV-1 DNA>3.0 log10 copies/10 PBMCs compared with other patients (95% CI: 1.24 to 3.80, P=0.007). The only other factor associated with progression was follow-up CD4 count (hazard ratio=1.23 per 100 cells/mm decrease; 95% CI: 1.07 to 1.41, P=0.003). DISCUSSION: PBMC HIV-1 DNA level was strongly associated with HIV-1 disease progression, even after adjusting for HIV-1 RNA and CD4 T-cell count. Further studies should assess whether patients with high HIV-1 DNA levels should start antiretroviral therapy earlier than other patients.

Incidence and determinants of mortality and morbidity following early antiretroviral therapy initiation in HIV-infected adults in West Africa.

OBJECTIVE: To estimate the incidence and risk factors of mortality and severe morbidity during the first months following antiretroviral therapy (ART) initiation in West African adults. METHODS: A cohort study in Abidjan in which 792 adults started ART with a median CD4 cell count of 252 cells/mul and were followed for a median of 8 months. Severe morbidity was defined as all World Health Organization stage 3 or 4-defining morbidity events other than oral candidiasis. RESULTS: In patients with pre-ART CD4 cell count < 200, at 200-350 and > 350 cells/mul, incidence of mortality was 5.0 [95% confidence interval (CI), 2.6-8.7], 1.7 (95% CI, 0.6-3.8) and 0.0 (95% CI, 0.0-3.4]/100 person-years, and incidence of severe morbidity was 13.3 (95% CI, 9.0-19.1), 9.5 (95% CI, 6.2-12.9) and 7.9 (95% CI, 3.4-15.5)/100 person-years, respectively. The most frequent diseases were invasive bacterial diseases (32/65 episodes, 49%) and tuberculosis (25/65 episodes, 38%). Both diseases followed the same curve of decreasing incidence over time. Patients who experienced severe morbidity had higher risks of mortality, virological failure and immunological failure. Other independent risk factors for mortality and/or severe morbidity were: at baseline, high viral load, advanced clinical stage, past history of tuberculosis, low BMI, low haemoglobin and low CD4 cell count; during follow-up: low CD4 cell count and persistently detectable viral load. CONCLUSION: These data give new arguments to reinforce the hypothesis that, in this region, ART should be started before the CD4 cell count drops below 350 cells/mul. Further studies should assess whether patients with low BMI, low haemoglobin, high viral load or past history of tuberculosis should start ART earlier.

Progression to WHO criteria for antiretroviral therapy in a 7-year cohort of adult HIV-1 seroconverters in Abidjan, Côte d'Ivoire.

OBJECTIVE: To estimate the probability of reaching the criteria for starting highly active antiretroviral therapy (HAART) in a prospective cohort of adult HIV-1 seroconverters in Abidjan, Côte d'Ivoire. METHODS: We recruited participants from HIV-positive donors at the blood bank of Abidjan for whom the delay since the estimated date of seroconversion (midpoint between last negative and first positive HIV-1 test) was < 36 months. Participants were offered early trimethoprim-sulfamethoxazole (cotrimoxazole) prophylaxis, twice-yearly measurement of CD4 count and we made standardized records of morbidity. We used the Kaplan-Meier method to estimate the probability of reaching the criteria for starting HAART according to WHO 2006 guidelines. FINDINGS: 217 adults (77 women (35%)) were followed up during 668 person-years (PY). The most frequent diseases recorded were mild bacterial diseases (6.0 per 100 PY), malaria (3.6/100 PY), herpes zoster (3.4/100 PY), severe bacterial diseases (3.1/100 PY) and tuberculosis (2.1/100 PY). The probability of reaching the WHO 2006 criteria for HAART initiation was estimated at 0.09, 0.16, 0.24, 0.36 and 0.44 at 1, 2, 3, 4 and 5 years, respectively. CONCLUSION: Our data underline the incidence of the early HIV morbidity in an Ivorian adult population and provide support for HIV testing to be made more readily available and for early follow-up of HIV-infected adults in West Africa.

Tolerance and acceptability of an efavirenz-based regimen in 740 adults (predominantly women) in West Africa.

In sub-Saharan Africa, the position of efavirenz as a first-line nonnucleoside reverse transcriptase inhibitor remains to be discussed. We report here the 6-month efficacy and tolerance of an efavirenz-containing highly active antiretroviral therapy in a large cohort of HIV-1-infected adults. Seven hundred forty highly active antiretroviral therapy-naive adults (74% women; 14% with positive serum HBs antigen and 21% with abnormal baseline transaminase value) started zidovudine + lamivudine + efavirenz. At month 6, 1.2% of them were dead, 87% had undetectable viral load, and 7% had abnormal transaminase value. From months 1 to 6, the percentage of women who were actually using a contraceptive method increased from 58% to 80% (65% intramuscular progesterone and 35% oral estrogen/progesterone combination). The incidence of pregnancy was 2.6/100 woman-years (95% confidence interval, 0.67-4.51), and 86% of pregnant women voluntarily interrupted the pregnancy with no intervention on our part. Before month 6, only 0.8% of patients permanently discontinued efavirenz for severe adverse effects (neurologic, 0.6%; cutaneous, 0.1%; and hepatic, 0.1%). The leading cause of severe morbidity was tuberculosis. Considering the very high hepatic and cutaneous tolerance, efavirenz could be considered as a valuable first-line drug for women of childbearing age who agree to use contraception in sub-Saharan Africa, provided that the risk of teratogenicity should be closely monitored.

Behavior assessment of blood donors facing the risk of HIV infection, Abidjan, Cotê D'Ivoire, 2001-2002.

Despite precautions taken to guarantee blood safety, in the National Blood Transfusion Center (CNTS) of Abidjan, about 30 regular blood donors are detected with HIV seroconversion each year, two-thirds of them men. A survey through face-to-face interviews was carried out at the CNTS of Abidjan from September 2001 to March 2002 among HIV-positive and HIV-negative regular blood donors, informed about their serologic status. HIV-negative regular blood donors informed about their serologic status since a median time of 67 months (n = 50) disclosed more risky behaviors such as multiple sexual partners (68%) than HIV-positive blood donors informed about their status (n = 112) since a median time of 35 months (41%) (P < 0.001). Condoms were systematically used by 17% of HIV-negative blood donors and 55% of HIV-positive blood donors (P < 0.001). Enhanced counseling and awareness could reduce in the future the number of cases of seroconversion among regular blood donors and improve their subsequent behavior. Blood donors who have unprotected sex with partners of unknown HIV serologic status and especially with casual partners are strongly exposed to HIV transmission and should be discouraged to continue giving blood, after adequate counseling.