El Bouzidi Kate, Datir Rawlings P, Kwaghe Vivian, Roy Sunando, Frampton Dan, Breuer Judith, Ogbanufe Obinna, Murtala-Ibrahim Fati, Charurat Man, Dakum Patrick, Sabin Caroline A, Ndembi Nicaise, Gupta Ravindra K. The Journal of antimicrobial chemotherapy 2022 77(2) 474-482

In 2018, an estimated 1.8 million persons living in Nigeria had HIV infection (1.3% of the total population), including 1.1 million (64%) who were receiving antiretroviral therapy (ART) (1). Effective ART reduces morbidity and mortality rates among persons with HIV infection and prevents HIV transmission once viral load is suppressed to undetectable levels (2,3). In April 2019, through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR),* CDC launched an 18-month ART Surge program in nine Nigerian states to rapidly increase the number of persons with HIV infection receiving ART. CDC analyzed programmatic data gathered during March 31, 2019-September 30, 2020, to describe the ART Surge program's progress on case finding, ART initiation, patient retention, and ART Surge program growth. Overall, the weekly number of newly identified persons with HIV infection who initiated ART increased approximately eightfold, from 587 (week ending May 4, 2019) to 5,329 (week ending September 26, 2020). The ART Surge program resulted in 208,202 more HIV-infected persons receiving PEPFAR-supported ART despite the COVID-19 pandemic (97,387 more persons during March 31, 2019-March 31, 2020 and an additional 110,815 persons during April 2020-September 2020). Comprehensive, data-guided, locally adapted interventions and the use of incident command structures can help increase the number of persons with HIV infection who receive ART, reducing HIV-related morbidity and mortality as well as decreasing HIV transmission.

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.

BACKGROUND: Nigeria has a high burden of HIV and tuberculosis (TB). To reduce TB-associated morbidity and mortality, the World Health Organization recommends that HIV-positive TB patients receive antiretroviral therapy (ART) within eight weeks of TB treatment initiation, or within two weeks if profoundly immunosuppressed (CD4<50 cell/μL). METHODS: TB and HIV clinical records from facilities in two Nigerian states between October 1(st), 2012 and September 30(th), 2013 were retrospectively reviewed to assess uptake and timing of ART initiation among HIV-positive TB patients. Healthcare workers were qualitatively interviewed to assess TB/HIV knowledge and barriers to timely ART. RESULTS: Data were abstracted from 4,810 TB patient records, of which 1,249 (26.0%) had HIV-positive or unknown HIV status documented, and the 574 (45.9%) HIV-positive TB patients were evaluated for timing of ART uptake relative to TB treatment. Among 484 (84.3%) HIV-positive TB patients not already on ART, 256 (52.9%, 95% CI: 45.0-60.8) were not initiated on ART during six months of TB treatment. 30.0% of 273 patients with a known CD4≥50cells/μL started ART within eight weeks, and 14.8% of 54 patients with a known CD4<50cells/μL started within the recommended two weeks. Only 42% of health workers interviewed reported knowing to interpret guidelines on when to initiate ART in HIV-positive TB patients based on CD4 cell count results. CD4 cell count significantly predicted timely ART uptake. CONCLUSION: A large proportion of HIV-positive TB patients were not initiated on ART early or even at all during TB treatment. Retraining of staff, and interventions to strengthen referral systems should be implemented to ensure timely provision of ART among HIV-positive TB patients in Nigeria.