First case report of a perinatally HIV-infected infant with HIV resistance to dolutegravir associated with tenofovir/lamivudine/dolutegravir use in mothers.

Perinatally HIV-infected infants can be infected with a drug-resistant virus or select for drug resistance by exposure to sub-therapeutic levels of maternal antiretroviral drugs present in breastmilk or from sub-therapeutic infant prophylaxis. We report a case of dolutegravir resistance detected in a treatment-naive perinatally HIV-infected infant whose mother was receiving tenofovir/lamivudine/dolutegravir. This case was detected during a national survey of HIV drug resistance in Haiti amongst infants testing positive for HIV through the national early infant diagnosis program between April 2020 and March 2021. This unique case underscores the need for prompt management of high viral loads in pregnant and breastfeeding women and supports HIV drug resistance surveillance efforts targeted at antiretroviral therapy-naive infants born to mothers in low-and middle-income countries.

Resistance levels to non-nucleoside reverse transcriptase inhibitors among pregnant women with recent HIV infection in Malawi.

BACKGROUND: Information on HIV drug resistance (HIVDR) prevalence in people newly diagnosed with HIV is limited. We implemented a cross-sectional study to estimate HIVDR prevalence among pregnant women recently infected with HIV in Malawi. METHODS: The HIVDR study was nested within a routine antenatal clinic (ANC) sentinel surveillance survey. Dried blood spot samples were tested for recent infection using a limiting antigen antibody assay together with HIV viral load testing. HIV-1 protease and reverse transcriptase were sequenced using Sanger sequencing. Drug susceptibility was predicted using Stanford HIVdb algorithm (version 8.9). Weighted analysis was performed in Stata 15.1. RESULTS: Of the 21,642 pregnant women enrolled in the ANC survey, 8.4% (1826/21,642) tested HIV positive. Of these, 5.0% (92/1826) had recent HIV infection, and 90.2% (83/92) were tested by PCR. The amplification and sequencing success rate was 57.8% (48/83). The prevalence of any HIVDR was 14.6% (5/45) (95% CI: 4.7-36.8%), all of which indicated HIVDR to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIVDR to nucleoside reverse transcriptase inhibitors was 7.9% (2/45) (95% CI: 1.4-34.6%). Resistance to protease inhibitors currently in use in Malawi was not observed. CONCLUSIONS: Despite the low number of cases with presumed TDR, our study hints that resistance to NNRTIs was high, above the 10% target for regimen change. Further investigation is needed to establish the exact magnitude of presumed TDR among women recently infected with HIV. These findings support the transition to an integrase inhibitor-based first-line regimen for patients initiating or on ART.

HIV drug resistance in persons initiating or reinitiating first-line antiretroviral therapy in Paraguay: Results of a National Patient Survey.

Human immunodeficiency virus (HIV) drug resistance increases mortality and morbidity and antiretroviral therapy (ART) costs. We describe Paraguay's first nationally representative survey on pretreatment drug resistance (PDR) conducted among persons who initiated or reinitiated ART in 2019. ​​​​We conducted a cross-sectional survey of antiretroviral (ARV) drug resistance in Paraguay in 2019. Participants were sampled at four comprehensive care clinics where 90% of patients with HIV in Paraguay initiate ART. Patients included were adults ≥18 years old who initiated first-line ART or reinitiated the same first-line ART regimen after ≥3 months of discontinuation. Of 208 patients, 93.8% had no prior ART exposure, 3.8% reinitiated the same regimen, 2.4% had unknown prior ART exposure; and 31.3% had a CD4 count <200 cells/µl. Mutations associated with resistance were present in 15.4% of patients. Mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTI) were present in 13.0% of patients, nucleoside reverse transcriptase inhibitors in 4.3%, and integrase inhibitors in 3.4%. Mutations associated with resistance to tenofovir were present in 1.0% of patients and emtricitabine/lamivudine in 1.4%. ​​Nearly one in six patients had PDR in Paraguay's first nationally representative sample. High NNRTI PDR prevalence underscores the need to accelerate the transition to dolutegravir-based first-line ART. The low PDR prevalence of tenofovir and emtricitabine is reassuring as these ARVs are part of the World Health Organization (WHO)-recommended oral pre-exposure prophylaxis regimen. The high proportion of individuals initiating ART at a late disease stage highlights the need to improve treatment linkage strategies and implement WHO rapid ART initiation recommendations.

Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence.

PURPOSE OF REVIEW: This review summarises the latest information of the epidemiology of HIV drug resistance (HIVDR) in low- and middle-income countries and the updated WHO global strategy for HIVDR surveillance and monitoring. RECENT FINDINGS: Finding from recent national-representative surveys show a rise in pretreatment drug resistance (PDR) to reverse transcriptase inhibitors and especially to the class of nonnucleoside reverse transcriptase inhibitors. Levels of PDR are especially high in infants <18 months and adults reporting prior exposure to antiretrovirals. Although viral suppression rates are generally high and increasing among adults on antiretroviral therapy, those with unsuppressed viremia have high levels of acquired drug resistance (ADR). Programmatic data on HIVDR to integrase-transfer-inhibitor resistance is scarce, highlighting the need to increase integrase-inhibitors resistance surveillance. As the landscape of HIV prevention, treatment and monitoring evolves, WHO has also adapted its strategy to effectively support countries in preventing and monitoring the emergence of HIVDR. This includes new survey methods for monitoring resistance emerging from patients diagnosed with HIV while on preexposure prophylaxis, and a laboratory-based ADR survey leveraging on remnant viral load specimens which are expected to strengthen dolutegravir-resistance surveillance. SUMMARY: Monitoring HIVDR remains pivotal to ensure countries attain and sustain the global goals for ending HIV as a public health threat by 2030.

Pretreatment Human Immunodeficiency Virus (HIV) Drug Resistance Among Treatment-Naive Infants Newly Diagnosed With HIV in 2016 in Namibia: Results of a Nationally Representative Study.

Background: The World Health Organization (WHO) recommends routine surveillance of pretreatment human immunodeficiency virus (HIV) drug resistance (HIVDR) in children <18 months of age diagnosed with HIV through early infant diagnosis (EID). In 2016, 262 children <18 months of age were diagnosed with HIV in Namibia through EID. Levels of HIVDR in this population are unknown. Methods: In 2016, Namibia surveyed pretreatment HIVDR among children aged <18 months following WHO guidance. Reverse transcriptase, protease, and integrase regions of HIV-1 were genotyped from remnant dried blood spot specimens from all infants diagnosed with HIV in Namibia in 2016. HIVDR was predicted using the Stanford HIVdb algorithm. Results: Of 262 specimens genotyped, 198 HIV-1 protease and reverse transcriptase sequences and 118 HIV-1 integrase sequences were successfully amplified and analyzed. The prevalence of efavirenz/nevirapine (EFV/NVP), abacavir (ABC), zidovudine, lamivudine/emtricitabine (3TC/FTC), and tenofovir (TDF) resistance was 62.6%, 17.7%, 5.6%, 15.7%, and 10.1%, respectively. No integrase inhibitor resistance was detected. Conclusions: The high level of EFV/NVP resistance is unsurprising; however, levels of ABC and TDF resistance are among the highest observed to date in infants in sub-Saharan Africa. The absence of resistance to dolutegravir (DTG) is reassuring but underscores the need to further study the impact of ABC and 3TC/FTC resistance on pediatric protease inhibitor- and DTG-based regimens and accelerate access to other antiretroviral drugs. Results underscore the need for antiretroviral therapy optimization and prompt management of high viral loads in infants and pregnant and breastfeeding women.

HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis.

BACKGROUND: Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether it is associated with the intiation or re-initiation of ART in people who have had previous exposure to antiretroviral drugs. METHODS: This study was a systematic review and meta-regression analysis. We assessed regional prevalence of pretreatment drug resistance and risk of pretreatment drug resistance in people initiating ART who reported previous ART exposure. We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs. We searched for studies in PubMed and Embase and conference abstracts and presentations from the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society Conference, and the International Drug Resistance Workshop for the period Jan 1, 2001, to Dec 31, 2016. To assess the prevalence of drug resistance within a specified region at any specific timepoint, we extracted study level data and pooled prevalence estimates within the region using an empty logistic regression model with a random effect at the study level. We used random effects meta-regression to relate sampling year to prevalence of pretreatment drug resistance within geographical regions. FINDINGS: We identified 358 datasets that contributed data to our analyses, representing 56 044 adults in 63 countries. Prevalence estimates of pretreatment NNRTI resistance in 2016 were 11·0% (7·5-15·9) in southern Africa, 10·1% (5·1-19·4) in eastern Africa, 7·2% (2·9-16·5) in western and central Africa, and 9·4% (6·6-13·2) in Latin America and the Caribbean. There were substantial increases in pretreatment NNRTI resistance per year in all regions. The yearly increases in the odds of pretreatment drug resistance were 23% (95% CI 16-29) in southern Africa, 17% (5-30) in eastern Africa, 17% (6-29) in western and central Africa, 11% (5-18) in Latin America and the Caribbean, and 11% (2-20) in Asia. Estimated increases in the absolute prevalence of pretreatment drug resistance between 2015 and 2016 ranged from 0·3% in Asia to 1·8% in southern Africa. INTERPRETATION: Pretreatment drug resistance is increasing at substantial rate in LMICs, especially in sub-Saharan Africa. In 2016, the prevalence of pretreatment NNRTI resistance was near WHO's 10% threshold for changing first-line ART in southern and eastern Africa and Latin America, underscoring the need for routine national HIV drug-resistance surveillance and review of national policies for first-line ART regimen composition. FUNDING: Bill & Melinda Gates Foundation and World Health Organization.

Prevalence and patterns of HIV transmitted drug resistance in Guatemala / Prevalencia y patrones de farmacorresistencia transmitida del VIH en Guatemala

Objective. To assess human immunodeficiency virus (HIV) diversity and the prevalence of transmitted drug resistance (TDR) in Guatemala. Methods. One hundred forty-five antiretroviral treatment-naïve patients referred to the Roosevelt Hospital in Guatemala City were enrolled from October 2010 to March 2011. Plasma HIV pol sequences were obtained and TDR was assessed with the Stanford algorithm and the World Health Organization (WHO) TDR surveillance mutation list. Results. HIV subtype B was highly prevalent in Guatemala (96.6%, 140/145), and a 2.8% (4/145) prevalence of BF1 recombinants and 0.7% (1/145) prevalence of subtype C viruses were found. TDR prevalence for the study period was 8.3% (12/145) with the Stanford database algorithm (score > 15) and the WHO TDR surveillance mutation list. Most TDR cases were associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) (83.3%, 10/12); a low prevalence of nucleoside reverse transcriptase inhibitors and protease inhibitors was observed in the cohort (< 1% for both families). Low selection of antiretroviral drug resistance mutations was found, except for NNRTI-associated mutations. Major NNRTI mutations such as K101E, K103N, and E138K showed higher frequencies than expected in ART-naïve populations. Higher literacy was associated with a greater risk of TDR (odds ratio 4.14, P = 0.0264). Conclusions. This study represents one of the first efforts to describe HIV diversity and TDR prevalence and trends in Guatemala. TDR prevalence in Guatemala was at the intermediate level. Most TDR cases were associated with NNRTIs. Further and continuous TDR surveillance is necessary to gain more in-depth knowledge about TDR spread and trends in Guatemala and to optimize treatment outcomes in the country.

Objetivo. Evaluar la diversidad del virus de la inmunodeficiencia humana (VIH) y la prevalencia de la farmacorresistencia transmitida en Guatemala. Métodos. Entre octubre del 2010 y marzo del 2011 se incluyeron en el estudio 145 pacientes no tratados anteriormente con antirretrovirales, derivados al Hospital Roosevelt en la Ciudad de Guatemala. Se obtuvieron las secuencias pol a partir del VIH plasmático y se evaluó la farmacorresistencia transmitida con el algoritmo de Stanford y la lista de mutaciones para la vigilancia de la farmacorresistencia transmitida de la Organización Mundial de la Salud (OMS). Resultados. El subtipo B del VIH fue sumamente prevalente en Guatemala (96,6%, 140/145), y se encontró una prevalencia de formas recombinantes BF1 de 2,8% (4/145) y una prevalencia del subtipo C del virus de 0,7% (1/145). La prevalencia de la farmacorresistencia transmitida durante el período de estudio fue de 8,3% (12/145) según el algoritmo de la base de datos de Stanford (puntuación > 15) y la lista de mutaciones para la vigilancia de la farmacorresistencia transmitida de la OMS. En la mayoría de los casos, la farmacorresistencia transmitida se asoció con los inhibidores de la transcriptasa inversa no análogos de nucleósidos (ITINN) (83,3%, 10/12); en la cohorte se observó una baja prevalencia asociada con los inhibidores de la transcriptasa inversa análogos de nucleósidos y con los inhibidores de la proteasa (< 1% para ambas familias de fármacos). Se encontró una baja selección de mutaciones causantes de farmacorresistencia debidas a los antirretrovirales, excepto en las mutaciones asociadas a los ITINN. Las mutaciones importantes relacionadas con los ITINN, como K101E, K103N y E138K, mostraron frecuencias más elevadas que las esperadas en las poblaciones vírgenes de tratamiento antirretroviral. En las personas con un nivel de escolaridad más elevado se encontró un mayor riesgo de farmacorresistencia transmitida (razón de posibilidades 4,14; P = 0,0264). Conclusiones. Este estudio representa uno de los primeros intentos de describir la diversidad del VIH, y la prevalencia de la farmacorresistencia transmitida y sus tendencias en Guatemala. La prevalencia de la farmacorresistencia transmitida en Guatemala presentó un nivel intermedio y en la mayoría de los casos se asoció con los ITINN. Se necesita una vigilancia más intensa y sostenida de la farmacorresistencia transmitida para conocer más exhaustivamente su grado de diseminación y sus tendencias en Guatemala, al igual que para optimizar los resultados del tratamiento antirretroviral en el país.

Prevalence and patterns of HIV transmitted drug resistance in Guatemala.

OBJECTIVE: To assess human immunodeficiency virus (HIV) diversity and the prevalence of transmitted drug resistance (TDR) in Guatemala. METHODS: One hundred forty-five antiretroviral treatment-naïve patients referred to the Roosevelt Hospital in Guatemala City were enrolled from October 2010 to March 2011. Plasma HIV pol sequences were obtained and TDR was assessed with the Stanford algorithm and the World Health Organization (WHO) TDR surveillance mutation list. RESULTS: HIV subtype B was highly prevalent in Guatemala (96.6%, 140/145), and a 2.8% (4/145) prevalence of BF1 recombinants and 0.7% (1/145) prevalence of subtype C viruses were found. TDR prevalence for the study period was 8.3% (12/145) with the Stanford database algorithm (score > 15) and the WHO TDR surveillance mutation list. Most TDR cases were associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) (83.3%, 10/12); a low prevalence of nucleoside reverse transcriptase inhibitors and protease inhibitors was observed in the cohort (< 1% for both families). Low selection of antiretroviral drug resistance mutations was found, except for NNRTI-associated mutations. Major NNRTI mutations such as K101E, K103N, and E138K showed higher frequencies than expected in ART-naïve populations. Higher literacy was associated with a greater risk of TDR (odds ratio 4.14, P = 0.0264). CONCLUSIONS: This study represents one of the first efforts to describe HIV diversity and TDR prevalence and trends in Guatemala. TDR prevalence in Guatemala was at the intermediate level. Most TDR cases were associated with NNRTIs. Further and continuous TDR surveillance is necessary to gain more indepth knowledge about TDR spread and trends in Guatemala and to optimize treatment outcomes in the country.