Barriers to early diagnosis of cervical cancer: a mixed-method study in Côte d'Ivoire, West Africa.

BACKGROUND: Cervical cancer, a major public health problem in many developing countries, is usually associated with a poor survival related to an advanced disease at diagnosis. In Côte d'Ivoire and other developing countries with high cervical cancer prevalence, little is known about factors associated with advanced cervical cancer stages in a context of limited access to screening services. METHODS: From May to July 2019, we conducted a cross-sectional study using a mixed, quantitative and qualitative method. Information on socio-demographic and history of the disease was extracted from a rapid case ascertainement study performed by the cancer registry of Côte d'Ivoire that enrolled all women diagnosed with cervical cancer between July 2018 and June 2019. In-depth semi-structured interviews were conducted among a subset of these women (12 women) and six healthcare providers to further capture barriers to early cervical cancer diagnosis. Factors associated with an advanced stage III, IV (according to FIGO classification) were estimated by a logistic regression model. Qualitative data were analyzed using a thematic analysis technique guided by the treatment pathway model and triangulated with quantitative data. RESULTS: In total, 95 women with cervical cancer [median age = 51 (IQR 42-59)] years, were included. Among them, 18.9% were living with HIV and only 9.5% were covered by a health insurance. The majority (71.5%) were diagnosed with advanced cervical cancer. Being HIV-uninfected (aOR = 5.4; [1.6-17.8], p = 0.006) and being uninsured (aOR = 13.1; [2.0-85.5], p = 0.007) were independently associated with advanced cervical cancer in multivariable analysis. Qualitative data raised additional factors potentially related to advanced cervical cancer stages at diagnosis, including the lack of patient information on cervical cancer by healthcare providers and inadequate national awareness and screening campaigns. CONCLUSION: In a context of challenges in access to systematic cervical cancer screening in Côte d'Ivoire, access to health insurance or integrated healthcare program appear to be key determinants of early diagnosis of cervical cancer.

Eliminating postnatal HIV transmission in high incidence areas: need for complementary biomedical interventions.

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies.

Impact of Next-generation Sequencing Defined Human Immunodeficiency Virus Pretreatment Drug Resistance on Virological Outcomes in the ANRS 12249 Treatment-as-Prevention Trial.

BACKGROUND: Previous studies in human immunodeficiency virus (HIV)-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS; <50 copies/mL) in individuals prescribed primarily tenofovir/emtricitabine/efavirenz in rural KwaZulu-Natal within a treatment-as-prevention trial. METHODS: Among 1557 HIV-positive individuals who reported no prior ART at study entry and provided plasma samples, 1328 individuals with entry viral load (VL) >1000 copies/mL had next-generation sequencing (NGS) of the HIV pol gene with MiSeq technology. Results were obtained for 1148 individuals, and the presence of PDR was assessed at 5% and 20% detection thresholds. Virological outcome was assessed using Cox regression in 837 of 920 ART initiators with at least 1 follow-up VL after ART initiation. RESULTS: PDR prevalence was 9.5% (109/1148) and 12.8% (147/1148) at 20% and 5% thresholds, respectively. After a median of 1.36 years (interquartile range, 0.91-2.13), mostly on fixed-dose combination tenofovir/emtricitabine/efavirenz, presence of both nonnucleoside reverse transcriptase inhibitor (NNRTI)/nucleoside reverse transcriptase inhibitor PDR vs no PDR was associated with longer time to VS (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.12-0.86), while there was no difference between those with only NNRTI PDR vs no PDR (aHR, 1.05; 95% CI, 0.82-1.34) at the 5% threshold. Similar differences were observed for mutations detected at the 20% threshold, although without statistical significance. CONCLUSIONS: NGS uncovered a high prevalence of PDR among participants enrolled in trial clinics in rural KwaZulu-Natal. Dual-class PDR to a mainly tenofovir/emtricitabine/efavirenz regimen was associated with poorer VS. However, there was no impact of NNRTI PDR alone. CLINICAL TRIALS TEGISTRATION: NCT01509508; South African National Clinical Trials Register: DOH-27-0512-3974.

Protective effect of coffee consumption on all-cause mortality of French HIV-HCV co-infected patients.

BACKGROUND & AIMS: Coffee has anti-inflammatory and hepato-protective properties. In the general population, drinking ≥3cups of coffee/day has been associated with a 14% reduction in the risk of all-cause mortality. The aim of this study was to investigate the relationship between coffee consumption and the risk of all-cause mortality in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). METHODS: ANRS CO13 HEPAVIH is an ongoing French nationwide prospective cohort of patients co-infected with HIV-HCV collecting both medical and psychosocial/behavioural data (annual self-administered questionnaires). We used a Cox proportional hazards model to estimate the effect of elevated coffee consumption (≥3cups/day) at baseline on all-cause mortality during the cohort's five-year follow-up. RESULTS: Over a median [interquartile range] follow-up of 5.0 [3.9-5.9] years, 77 deaths occurred among 1,028 eligible patients (mortality rate 1.64/100 person-years; 95% confidence interval [CI] 1.31-2.05). Leading causes of death were HCV-related diseases (n=33, 43%), cancers unrelated to AIDS/HCV (n=9, 12%), and AIDS (n=8, 10%). At the first available visit, 26.6% of patients reported elevated coffee consumption. Elevated coffee consumption at baseline was associated with a 50% reduced risk of all-cause mortality (hazard ratio 0.5; CI 0.3-0.9; p=0.032), after adjustment for gender and psychosocial, behavioral and clinical time-varying factors. CONCLUSIONS: Drinking three or more cups of coffee per day halves all-cause mortality risk in patients co-infected with HIV-HCV. The benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in this population. LAY SUMMARY: Coffee has anti-inflammatory and hepato-protective properties but its effect on mortality risk has never been investigated in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). This study shows that elevated coffee consumption (≥3cups/day) halves all-cause mortality risk in patients co-infected with HIV-HCV. The benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in this population.

Physical function, grip strength and frailty in people living with HIV in sub-Saharan Africa: systematic review.

OBJECTIVE: To present the current knowledge on physical function, grip strength and frailty in HIV-infected patients living in sub-Saharan Africa, where the phenomenon is largely underestimated. METHODS: A systematic search was conducted on MEDLINE, Scopus and African Index Medicus. We reviewed articles on sub-Saharan African people living with HIV (PLHIV) >18 years old, published until November 2016. RESULTS: Of 537 articles, 12 were conducted in six African countries and included in this review. Five articles reported information on functional limitation and one on disability. Two of these five articles reported functional limitation (low gait speed) in PLHIV. Disability was observed in 27% and 3% of PLHIV living in rural and urban places, respectively. Two of three studies reporting grip strength reported lower grip strength (nearly 4 kg) in PLHIV in comparison with uninfected patients. One study reported that PLHIV were more likely to be frail than HIV-uninfected individuals (19.4% vs. 13.3%), whereas another reported no statistical difference. CONCLUSION: Decline in physical function, grip strength and frailty are now part of the burden of PLHIV living in SSA countries, but current data are insufficient to characterise the real public health dimension of these impairments. Further studies are needed to depict this major public health challenge. As this is likely to contribute to a significant burden on the African healthcare systems and human resources in the near future, a holistic care approach should be developed to inform guidelines.

HIV infection, viral hepatitis and liver fibrosis among prison inmates in West Africa.

BACKGROUND: Prisoners represent a vulnerable population for blood-borne and sexually transmitted infections which can potentially lead to liver fibrosis and ultimately cirrhosis. However, little is known about the prevalence of liver fibrosis and associated risk factors among inmates in sub-Saharan Africa. METHODS: Screening of liver fibrosis was undertaken in a randomly selected sample of male inmates incarcerated in Lome, Togo and in Dakar, Senegal using transient elastography. A liver stiffness measurement ≥9.5 KPa was retained to define the presence of a severe liver fibrosis. All included inmates were also screened for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Substances abuse including alcohol, tobacco and cannabis use were assessed during face-to-face interviews. Odds Ratio (OR) estimates were computed with their 95 % Confidence Interval (CI) to identify factors associated with severe liver fibrosis. RESULTS: Overall, 680 inmates were included with a median age of 30 years [interquartile range: 24-35]. The prevalence of severe fibrosis was 3.1 % (4.9 % in Lome and 1.2 % in Dakar). Infections with HIV, HBV and HCV were identified in 2.6 %, 12.5 % and 0.5 % of inmates, respectively. Factors associated with a severe liver fibrosis were HIV infection (OR = 7.6; CI 1.8-32.1), HBV infection (OR = 4.8; CI 1.8-12.8), HCV infection (OR = 52.6; CI 4.1-673.8), use of traditional medicines (OR = 3.7; CI 1.4-10.1) and being incarcerated in Lome (OR = 3.3; CI 1.1-9.8) compared to Dakar. CONCLUSIONS: HIV infection and viral hepatitis infections were identified as important and independent determinants of severe liver fibrosis. While access to active antiviral therapies against HIV and viral hepatitis expands in Africa, adapted strategies for the monitoring of liver disease need to be explored, especially in vulnerable populations such as inmates.

Change of treatment guidelines and evolution of ART initiation in rural South Africa: data of a large HIV care and treatment programme.

BACKGROUND: While WHO recommendations are to treat people earlier and earlier, it will considerably increase the number of HIV infected people eligible for antiretroviral therapy (ART). In South Africa, a country which carries one of the highest HIV burden worldwide, very few studies are available on the impact of the ART guidelines on time to ART initiation in both individuals with low CD4 count and those newly eligible for ART. We thus aimed to describe ART initiation percentages in a large HIV programme in rural KwaZulu-Natal, South Africa, according to the temporal changes of national ART eligibility guidelines from 2007 to 2012. METHODS: Adults who accessed the decentralized Hlabisa HIV treatment programme in 2007-2012 were included. Three periods following the temporal change of ART eligibility guidelines were defined (Period 1: until April 2010; Period 2: April 2010 - July 2011; Period 3: from August 2011). Percentages of ART initiation within three months of programme entry were estimated in men, in women of childbearing age (<40 years old) and in older women, and stratifying by CD4 count. Trend tests and logistic regression models were used to study the effects of change of guidelines on ART initiation percentages. RESULTS: In individuals with CD4 count ≤200 cells/µL (N = 5709 men, N = 6743 women <40 years old and N = 2017 older women), percentages of ART initiation did not differ over time (p trend = 0.25; 0.28; and 0.14, respectively). In individuals with CD4 count = 201-350 cells/µL (N = 2680 men, N = 6086 women <40 years old and N = 1415 older women), percentages of ART initiation significantly increased over time (p trend <0.01 for the three groups): from 6 % in Period 1 to 20 % in Period 2 to 40 % in Period 3 in women of childbearing age, and from 7 % to 8-10 % to 42 % in men and in older women. CONCLUSIONS: As temporal changes of guidelines, percentages of ART initiation significantly increased in newly ART eligible people and did not decrease in individuals with very low CD4 counts. It will be crucial to continue verifying the evolution of these percentages of ART initiation with future recommendations reaching near-to-universal access to ART, to ensure that individuals most in need of ART receive it.

Cervical cancer prevention in reproductive health services: knowledge, attitudes and practices of midwives in Côte d'Ivoire, West Africa.

BACKGROUND: Cervical cancer is the most common cancer among women and the leading cause of cancer deaths in women in Côte d'Ivoire. Low resource countries can now prevent this cancer by using HPV vaccine and effective and affordable screening tests. However the implementation of these prevention strategies needs well-trained human resources. Part of the solution could come from midwives by integrating cervical cancer prevention into reproductive health services. The aim of this survey was to assess knowledge, attitudes and practices of midwives towards cervical cancer prevention in Abidjan, Côte d'Ivoire, and to find out factors associated with appropriate knowledge. METHODS: A cross-sectional survey was conducted among midwives in the urban district of Abidjan, using a self-administered questionnaire. Knowledge was assessed by two scores. Factors associated with appropriate knowledge were determined using a logistic regression analysis. Attitudes and practices were described and compare using the Chi2 test. RESULTS: A total of 592 midwives were enrolled, including 24.5% of final-year students. 55.7% of midwives had appropriate knowledge on cervical cancer, and 42.4% of them had appropriate knowledge on cervical cancer prevention strategies. Conferences, courses taken at school of midwifery and special training sessions on cervical cancer (OR = 4.9, 95% CI [1.9 to 12.6], p <0.01) were associated with good knowledge on the management of this disease. Among these midwives, 18.4% had already benefited from a screening test for themselves, 37.7% had already advised screening to patients and 8.4% were able to perform a visual inspection. 50.3% of midwives knew HPV vaccine as a preventive method; among them 70.8% usually recommended it to young girls. CONCLUSION: Despite sufficient knowledge about cervical cancer prevention, attitudes and practices of midwives should be improved by organizing capacity building activities. This would ensure the success of integration of cervical cancer prevention into reproductive health services in countries like Côte d'Ivoire.

Oral lesions among HIV-infected children on antiretroviral treatment in West Africa.

OBJECTIVE: To estimate the prevalence of oral mucosal diseases and dental caries among HIV-infected children receiving antiretroviral treatment (ART) in West Africa and to identify the factors associated with the prevalence of oral mucosal lesions. METHODS: Multicentre cross-sectional survey in five paediatric HIV clinics in Côte d'Ivoire, Mali and Sénégal. A standardised examination was performed by trained dentists on a random sample of HIV-infected children aged 5-15 years receiving ART. The prevalence of oral and dental lesions and mean number of decayed, missing/extracted and filled teeth (DMFdefT) in temporary and permanent dentition were estimated with their 95% confidence interval (95% CI). We used logistic regression to explore the association between children's characteristics and the prevalence of oral mucosal lesions, expressed as prevalence odds ratio (POR). RESULTS: The median age of the 420 children (47% females) enrolled was 10.4 years [interquartile range (IQR) = 8.3-12.6]. The median duration on ART was 4.6 years (IQR = 2.6-6.2); 84 (20.0%) had CD4 count<350 cells/mm(3). A total of 35 children (8.3%; 95% CI: 6.1-11.1) exhibited 42 oral mucosal lesions (24 were candidiasis); 86.0% (95% CI = 82.6-89.3) of children had DMFdefT ≥ 1. The presence of oral mucosal lesions was independently associated with CD4 count < 350 cells/mm(3) (POR = 2.96, 95% CI = 1.06-4.36) and poor oral hygiene (POR = 2.69, 95% CI = 1.07-6.76). CONCLUSIONS: Oral mucosal lesions still occur in HIV-infected African children despite ART, but rarely. However, dental caries were common and severe in this population, reflecting the need to include oral health in the comprehensive care of HIV.

Association between elevated coffee consumption and daily chocolate intake with normal liver enzymes in HIV-HCV infected individuals: results from the ANRS CO13 HEPAVIH cohort study.

BACKGROUND & AIMS: We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. METHODS: Longitudinal data collection included self-administered questionnaires and medical data (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (≥3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 × upper normal limit (UNL)) (N=990) over time, after adjustment for known correlates. Logistic regression models based on generalized estimating equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio. RESULTS: After adjustment, patients reporting elevated coffee consumption and daily chocolate intake were less likely to present abnormal ALT (OR=0.65; p=0.04 and OR=0.57; p=0.04, for coffee and chocolate respectively), while only patients reporting elevated coffee consumption were less likely to have abnormal AST values (p=0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with approximately 40% reduced risk of abnormal liver enzymes (p=0.003 for AST; p=0.002 for ALT). CONCLUSIONS: Elevated coffee consumption and daily chocolate intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury.

WHO 2010 guidelines for prevention of mother-to-child HIV transmission in Zimbabwe: modeling clinical outcomes in infants and mothers.

BACKGROUND: The Zimbabwean national prevention of mother-to-child HIV transmission (PMTCT) program provided primarily single-dose nevirapine (sdNVP) from 2002-2009 and is currently replacing sdNVP with more effective antiretroviral (ARV) regimens. METHODS: Published HIV and PMTCT models, with local trial and programmatic data, were used to simulate a cohort of HIV-infected, pregnant/breastfeeding women in Zimbabwe (mean age 24.0 years, mean CD4 451 cells/µL). We compared five PMTCT regimens at a fixed level of PMTCT medication uptake: 1) no antenatal ARVs (comparator); 2) sdNVP; 3) WHO 2010 guidelines using "Option A" (zidovudine during pregnancy/infant NVP during breastfeeding for women without advanced HIV disease; lifelong 3-drug antiretroviral therapy (ART) for women with advanced disease); 4) WHO "Option B" (ART during pregnancy/breastfeeding without advanced disease; lifelong ART with advanced disease); and 5) "Option B+:" lifelong ART for all pregnant/breastfeeding, HIV-infected women. Pediatric (4-6 week and 18-month infection risk, 2-year survival) and maternal (2- and 5-year survival, life expectancy from delivery) outcomes were projected. RESULTS: Eighteen-month pediatric infection risks ranged from 25.8% (no antenatal ARVs) to 10.9% (Options B/B+). Although maternal short-term outcomes (2- and 5-year survival) varied only slightly by regimen, maternal life expectancy was reduced after receipt of sdNVP (13.8 years) or Option B (13.9 years) compared to no antenatal ARVs (14.0 years), Option A (14.0 years), or Option B+ (14.5 years). CONCLUSIONS: Replacement of sdNVP with currently recommended regimens for PMTCT (WHO Options A, B, or B+) is necessary to reduce infant HIV infection risk in Zimbabwe. The planned transition to Option A may also improve both pediatric and maternal outcomes.

Participation of traditional birth attendants in prevention of mother-to-child transmission of HIV services in two rural districts in Zimbabwe: a feasibility study.

BACKGROUND: Prevention of Mother-to-Child Transmission of HIV (PMTCT) is among the key HIV prevention strategies in Zimbabwe. A decrease in use of antenatal care (ANC) services with an increase in home deliveries is affecting the coverage of PMTCT interventions in a context of accelerated economic crisis. The main objective was to evaluate acceptability and feasibility of reinforcing the role of traditional birth attendants (TBAs) in family and child health services through their participation in PMTCT programmes in Zimbabwe. METHODS: A community based cross-sectional survey was undertaken using multistage cluster sampling in two rural districts through interviews and focus group discussions among women who delivered at home with a TBA, those who had an institutional delivery and TBAs. RESULTS: 45% of TBAs interviewed knew the principles of PMTCT and 8% delivered a woman with known HIV-positive status in previous year. Of the complete package of PMTCT services, more than 75% of TBAs agreed to participate in most activities with the exception of performing a blood test (17%), accompanying newborns to closest health centre to receive medication (15%) and assisting health centres in documentation of the link ANC-PMTCT services (18%). Women who delivered at home were less likely to have received more than one ANC service or have had contact with a health centre compared to women who delivered in a health centre (91.0% vs 72.6%; P < 0.001). Also, 63.6% of the women who delivered in a health centre had the opportunity to choose the place of delivery compared to 39.4% of women who delivered at home (P < 0.001). More than 85% of women agreed that TBAs could participate in all activities related to a PMTCT programme with the exception of performing a blood test for HIV. Concerns were highlighted regarding confidentiality of the HIV-serostatus of women. CONCLUSION: Although the long-term goal of ANC service delivery in Zimbabwe remains the provision of skilled delivery attendance, PMTCT programmes will benefit from complementary approaches to prevent missed opportunities. TBAs are willing to expand their scope of work regarding activities related to PMTCT. There is a need to reinforce their knowledge on MTCT prevention measures and better integrate them into the health system.

Maternal 12-month response to antiretroviral therapy following prevention of mother-to-child transmission of HIV type 1, Ivory Coast, 2003-2006.

OBJECTIVE: Our aim was to study the response to antiretroviral treatment among women exposed to single-dose nevirapine (NVP) and/or short-course zidovudine (ZDV; with or without lamivudine [3TC]) for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) infection. METHODS: All HIV type 1-infected women who initiated antiretroviral treatment with stavudine or ZDV, 3TC, and NVP or efavirenz were eligible for the MTCT-Plus program in Abidjan, Ivory Coast. Exposed women had received either single-dose NVP alone or short-course ZDV (with or without 3TC) plus single-dose NVP during previous pregnancy. Genotypic resistance testing was performed at week 4 after delivery. Virologic failure was defined as a plasma HIV RNA level >500 copies/mL 12 months after initiation of antiretroviral treatment. RESULTS: Among 247 women who received antiretroviral treatment, 109 (44%) were unexposed; 81 had received short-course ZDV with 3TC, as well as single-dose NVP; 5 had received short-course ZDV plus 3TC; 50 had received short-course ZDV plus single-dose NVP; and 2 had received single-dose NVP alone. No ZDV mutation was detected in the 115 women whose specimens were available for genotypic testing; 11 (15.1%) of 73 women with 3TC exposure who were tested after delivery had 3TC resistance mutations. Three (4.3%) of 69 women exposed to short-course ZDV and 3TC plus single-dose NVP and 16 (38.1%) of 42 women exposed to short-course ZDV plus single-dose NVP had NVP resistance mutations. Antiretroviral treatment was initiated a median of 21 months after the intervention to prevent mother-to-child HIV transmission (median CD4(+) T lymphocyte count, 188 cells/mm(3)). Month 12 virologic failure was identified in 42 (19.2%) of 219 women for whom data were available, and multivariate analysis revealed that it was associated with poor adherence to treatment (adjusted odds ratio [aOR], 12.7; 95% confidence interval [CI], 3.0-53.9), postpartum 3TC resistance mutations (aOR, 6.9; 95% CI, 1.1-42.9), and a baseline CD4(+) T lymphocyte count <200 cells/mm(3) (aOR, 0.3; 95% CI, 0.2-0.8). NVP resistance was not associated with virological failure (aOR, 1.8; 95% CI, 0.5-6.5). CONCLUSIONS: Our study found that poor adherence and 3TC resistance acquired after the intervention to prevent mother-to-child transmission of HIV infection were associated with virologic failure in women who initiated antiretroviral treatment.