High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.

OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists. RESULTS: Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005). CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.K.E.B. is supported by Wellcome Trust award number 170461. N.N. is supported by NIH R01 AI147331-01. R.K.G. is supported by a Wellcome Trust Senior Fellowship in Clinical Science (WT108082AIA). This study was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of U2G GH002099-01 and PA GH17-1753 (ACHIEVE)

Rising HIV prevalence among men who have sex with men in Nigeria: A trend analysis

Background: Men who have sex with men (MSM) are conservatively estimated to be less than 1% of the Nigerian population yet nationally account for about 20% of new HIV infection. We estimated the trend in HIV prevalence and determined correlates of HIV infection among MSM. Methods: This study used data from respondent-driven sampling in three rounds of integrated biological and behavioral surveillance survey (2007, 2010 and 2014) and covered three states in 2007, six states in 2010 and eight states in 2014. Each round used similar methodology and thus allows for comparison. Behavioral data were obtained using a structured pre-coded questionnaire. Differences in categorical variables were assessed with Chi Square. Logistic regression was used to identify factors associated with HIV. Results: A total of 879, 1545 and 3611 MSM were recruited in 2007, 2010 and 2014 respectively. Median age was 22 years for 2007 and 2014 while it was 24 years in 2010. About one-third of MSM in 2007 and 2014 and about two-fifths in 2010 had engaged in transactional sex. HIV prevalence increased from 14% in 2007 to 17% in 2010 to 23% in 2014 (p \u3c 0.0001). Factors associated with HIV include older age ≥ 25 years (adjusted odds ratio {AOR}:2.41; 95% CI:1.84–3.16); receptive anal sex (AOR:1.92; 95% CI:1.54–2.40) and history of sexually transmitted infections (AOR:1.26; 95% CI:1.02–1.55). Conclusion: There’s been a consistent and significant increase in HIV prevalence among MSM with about 10-percentage points relative increase per year over 7 years. Older MSM were more likely to be HIV positive and this may reflect their prolonged exposure to high risk sexual activities. Evidence based interventions are urgently needed to mitigate intra-group HIV transmission and propagation of HIV epidemic between MSM and the general population

The pattern of attrition from an antiretroviral treatment program in Nigeria.

To evaluate the rate and factors associated with attrition of patients receiving ART in tertiary and secondary hospitals in Nigeria.We reviewed patient level data collected between 2007 and 2010 from 11 hospitals across Nigeria. Kaplan-Meier product-limit and Cox regression were used to determine probability of retention in care and risk factors for attrition respectively. Of 6,408 patients in the cohort, 3,839 (59.9%) were females, median age of study population was 33years (IQR: 27-40) and 4,415 (69%) were from secondary health facilities. The NRTI backbone was Stavudine (D4T) in 3708 (57.9%) and Zidovudine (ZDV) in 2613 (40.8%) of patients. Patients lost to follow up accounted for 62.7% of all attrition followed by treatment stops (25.3%) and deaths (12.0%). Attrition was 14.1 (N = 624) and 15.1% (N = 300) in secondary and tertiary hospitals respectively (p = 0.169) in the first 12 months on follow up. During the 13 to 24 months follow up period, attrition was 10.7% (N = 407) and 19.6% (N = 332) in secondary and tertiary facilities respectively (p<0.001). Median time to lost to follow up was 11.1 (IQR: 6.1 to 18.5) months in secondary compared with 13.6 (IQR: 9.9 to 17.0) months in tertiary sites (p = 0.002). At 24 months follow up, male gender [AHR 1.18, 95% CI: 1.01-1.37, P = 0.038]; WHO clinical stage III [AHR 1.30, 95%CI: 1.03-1.66, P = 0.03] and clinical stage IV [AHR 1.90, 95%CI: 1.20-3.02, p = 0.007] and care in a tertiary hospital [AHR 2.21, 95% CI: 1.83-2.67, p<0.001], were associated with attrition.Attrition could potentially be reduced by decentralizing patients on ART after the first 12 months on therapy to lower level facilities, earlier initiation on treatment and strengthening adherence counseling amongst males

Disengagement from HIV care and failure of second-line therapy in Nigeria: a retrospective cohort study, 2005-2017

BACKGROUND: Understanding the correlates of disengagement from HIV care and treatment failure during second-line antiretroviral therapy (ART) could inform interventions to improve clinical outcomes among people living with HIV (PLHIV). METHODS: We conducted a retrospective cohort study of PLHIV aged >15 years who started second-line ART at a tertiary centre in Nigeria between 2005 and 2017. Participants were considered to have disengaged from care if they had not returned within a year after each clinic visit. Cox proportional hazards models were used to investigate factors associated with: i) viral failure (HIV-1 RNA >1,000 copies/mL), ii) immunologic failure (CD4 count decrease or 10% of bodyweight), after >6 months of second-line ART. RESULTS: Among 1031 participants, 33% (341) disengaged from care during a median follow-up of 6.9 years (IQR 3.7-8.5). Of these, 26% (89/341) subsequently re-entered care. Disengagement was associated with male gender, age <30, lower education level and low CD4 count at second-line ART initiation. Among participants with endpoint assessments available, 20% (112/565) experienced viral failure, 32% (257/809) experienced immunologic failure, and 23% (190/831) experienced weight loss. A lower risk of viral failure was associated with professional occupations compared to elementary: adjusted hazard ratio 0.17 (95% confidence interval 0.04-0.70). CONCLUSION: Adverse outcomes were common during second-line ART. However, re-engagement is possible and resources should be allocated to focus on retaining PLHIV in care and providing services to trace and re-engage those who have disengaged from care

Treatment outcomes for all patients on ART at tertiary and secondary health facilities at 0–12 months follow up.

<p>Treatment outcomes for all patients on ART at tertiary and secondary health facilities at 0–12 months follow up.</p

Sexual Violence Prevalence and Related Pregnancy Among Girls and Young Women: A Multicountry Analysis

This study aims to quantify the prevalence of forced sex, pressured sex, and related pregnancy among adolescent girls and young women in five low- and middle-income countries. Nationally representative, cross-sectional household surveys were conducted in Haiti, Malawi, Nigeria, Zambia, and Uganda among girls and young women aged 13 to 24 years. A stratified three-stage cluster sample design was used. Respondents were interviewed to assess prevalence of sexual violence, pregnancy related to the first or most recent experience of forced or pressured sex, relationship to perpetrator, mean age at sexual debut, mean age at pregnancy related to forced or pressured sex, and prevalence of forced/coerced sexual debut. Frequencies, weighted percentages, and weighted means are presented. The lifetime prevalence of forced or pressured sex ranged from 10.4% to 18.0%. Among these adolescent girls and young women, the percentage who experienced pregnancy related to their first or most recent experience of forced or pressured sex ranged from 13.2% to 36.6%. In three countries, the most common perpetrator associated with the first pregnancy related to forced or pressured sex was a current or previous intimate partner. Mean age at pregnancy related to forced or pressured sex was similar to mean age at sexual debut in all countries. Preventing sexual violence against girls and young women will prevent a significant proportion of adverse effects on health, including unintended pregnancy. Implementation of strategies to prevent and respond to sexual violence against adolescent girls and young women is urgently needed

Cox Proportional Hazard Models between Attrition and Predictor Variables: 0–12 and 13–24 months on ART.

<p>Cox Proportional Hazard Models between Attrition and Predictor Variables: 0–12 and 13–24 months on ART.</p

Treatment outcomes for all patients on ART at tertiary and secondary health facilities at 13–24 months follow up.

<p>Treatment outcomes for all patients on ART at tertiary and secondary health facilities at 13–24 months follow up.</p

Baseline characteristics of the Study population.

*<p>Data available for 6,271 (Tertiary: 1917, Secondary: 4354).</p

Selected health care facilities.

<p>Selected health care facilities.</p